Abstract
By combining living cells with therapeutics, cell–drug conjugates can potentiate the functions of both components, particularly for applications in drug delivery and therapy. The conjugates can be designed to persist in the bloodstream, undergo chemotaxis, evade surveillance by the immune system, proliferate, or maintain or transform their cellular phenotypes. In this Review, we discuss strategies for the design of cell–drug conjugates with specific functions, the techniques for their preparation, and their applications in the treatment of cancers, autoimmune diseases and other pathologies. We also discuss the translational challenges and opportunities of this class of drug-delivery systems and therapeutics.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 digital issues and online access to articles
$99.00 per year
only $8.25 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Shi, J., Kantoff, P. W., Wooster, R. & Farokhzad, O. C. Cancer nanomedicine: progress, challenges and opportunities. Nat. Rev. Cancer 17, 20–37 (2017).
Manzari, M. T. et al. Targeted drug delivery strategies for precision medicines. Nat. Rev. Mater. 6, 351–370 (2021).
Mura, S., Nicolas, J. & Couvreur, P. Stimuli-responsive nanocarriers for drug delivery. Nat. Mater. 12, 991–1003 (2013).
Sun, W., Hu, Q., Ji, W., Wright, G. & Gu, Z. Leveraging physiology for precision drug delivery. Physiol. Rev. 97, 189–225 (2017).
Vargason, A. M., Anselmo, A. C. & Mitragotri, S. The evolution of commercial drug delivery technologies. Nat. Biomed. Eng. 5, 951–967 (2021).
Grimaldi, N. et al. Lipid-based nanovesicles for nanomedicine. Chem. Soc. Rev. 45, 6520–6545 (2016).
Hou, X., Zaks, T., Langer, R. & Dong, Y. Lipid nanoparticles for mRNA delivery. Nat. Rev. Mater. 6, 1078–1094 (2021).
Borandeh, S., van Bochove, B., Teotia, A. & Seppala, J. Polymeric drug delivery systems by additive manufacturing. Adv. Drug Deliv. Rev. 173, 349–373 (2021).
Li, F. et al. Spatiotemporally programmable cascade hybridization of hairpin DNA in polymeric nanoframework for precise siRNA delivery. Nat. Commun. 12, 1138 (2021).
Liu, Z. & Chen, X. Simple bioconjugate chemistry serves great clinical advances: albumin as a versatile platform for diagnosis and precision therapy. Chem. Soc. Rev. 45, 1432–1456 (2016).
Peer, D. et al. Nanocarriers as an emerging platform for cancer therapy. Nat. Nanotechnol. 2, 751–760 (2007).
Anselmo, A., Gokarn, Y. & Mitragotri, S. Non-invasive delivery strategies for biologics. Nat. Rev. Drug Discov.18, 19–40 (2019).
Wang, Y. et al. Peptide–drug conjugates as effective prodrug strategies for targeted delivery. Adv. Drug Deliv. Rev. 110, 112–126 (2017).
Cooper, B. M., Iegre, J., O’Donovan, D. H., Olwegard Halvarsson, M. & Spring, D. R. Peptides as a platform for targeted therapeutics for cancer: peptide–drug conjugates (PDCs). Chem. Soc. Rev. 50, 1480–1494 (2021).
Beck, A., Goetsch, L., Dumontet, C. & Corvaia, N. Strategies and challenges for the next generation of antibody–drug conjugates. Nat. Rev. Drug Discov. 16, 315–337 (2017).
Drago, J. Z., Modi, S. & Chandarlapaty, S. Unlocking the potential of antibody–drug conjugates for cancer therapy. Nat. Rev. Clin. Oncol. 18, 327–344 (2021).
Ekladious, I., Colson, Y. L. & Grinstaff, M. W. Polymer–drug conjugate therapeutics: advances, insights and prospects. Nat. Rev. Drug Discov. 18, 273–294 (2019).
Zhao, Z., Ukidve, A., Kim, J. & Mitragotri, S. Targeting strategies for tissue-specific drug delivery. Cell 181, 151–167 (2020).
Combes, F., Meyer, E. & Sanders, N. N. Immune cells as tumor drug delivery vehicles. J. Control. Release 327, 70–87 (2020).
Timin, A. S. et al. Cell-based drug delivery and use of nano- and microcarriers for cell functionalization. Adv. Healthc. Mater. 7, 1700818 (2018).
Yu, H., Yang, Z., Li, F., Xu, L. & Sun, Y. Cell-mediated targeting drugs delivery systems. Drug Deliv. 27, 1425–1437 (2020).
Su, Y., Xie, Z., Kim, G. B., Dong, C. & Yang, J. Design strategies and applications of circulating cell-mediated drug delivery systems. ACS Biomater. Sci. Eng. 1, 201–217 (2015).
Chen, Z., Hu, Q. & Gu, Z. Leveraging engineering of cells for drug delivery. Acc. Chem. Res. 51, 668–677 (2018).
Wang, Q. et al. Non-genetic engineering of cells for drug delivery and cell-based therapy. Adv. Drug Deliv. Rev. 91, 125–140 (2015).
Yoo, J. W., Irvine, D. J., Discher, D. E. & Mitragotri, S. Bio-inspired, bioengineered and biomimetic drug delivery carriers. Nat. Rev. Drug Discov. 10, 521–535 (2011).
Csizmar, C. M., Petersburg, J. R. & Wagner, C. R. Programming cell–cell interactions through non-genetic membrane engineering. Cell Chem. Biol. 25, 931–940 (2018).
Li, W., Su, Z., Hao, M., Ju, C. & Zhang, C. Cytopharmaceuticals: an emerging paradigm for drug delivery. J. Control. Release 328, 313–324 (2020).
Xue, J. et al. Neutrophil-mediated anticancer drug delivery for suppression of postoperative malignant glioma recurrence. Nat. Nanotechnol. 12, 692–700 (2017).
Xie, Z. et al. Immune cell-mediated biodegradable theranostic nanoparticles for melanoma targeting and drug delivery. Small 13, 1603121 (2017).
Wu, Q. et al. Inhibition of tumor metastasis by liquid-nitrogen-shocked tumor cells with oncolytic viruses infection. Adv. Mater. 35, 2212210 (2023).
Sun, P. et al. A smart nanoparticle-laden and remote-controlled self-destructive macrophage for enhanced chemo/chemodynamic synergistic therapy. ACS Nano 14, 13894–13904 (2020).
Zhang, W. et al. Nanoparticle-laden macrophages for tumor-tropic drug delivery. Adv. Mater. 30, 1805557 (2018).
Li, C. X. et al. Artificially reprogrammed macrophages as tumor-tropic immunosuppression-resistant biologics to realize therapeutics production and immune activation. Adv. Mater. 31, 1807211 (2019).
Evans, M. A. et al. Macrophage‐mediated delivery of hypoxia‐activated prodrug nanoparticles. Adv. Ther. 3, 1900162 (2019).
Stephan, M. T. & Irvine, D. J. Enhancing cell therapies from the outside in: cell surface engineering using synthetic nanomaterials. Nano Today 6, 309–325 (2011).
Ayer, M. et al. T cell-mediated transport of polymer nanoparticles across the blood–brain barrier. Adv. Healthc. Mater. 10, 2001375 (2021).
Tang, L. et al. Enhancing T cell therapy through TCR-signaling-responsive nanoparticle drug delivery. Nat. Biotechnol. 36, 707–716 (2018).
Xie, S. et al. Doxorubicin-conjugated Escherichia coli Nissle 1917 swimmers to achieve tumor targeting and responsive drug release. J. Control. Release 268, 390–399 (2017).
Stephan, M. T., Moon, J. J., Um, S. H., Bershteyn, A. & Irvine, D. J. Therapeutic cell engineering with surface-conjugated synthetic nanoparticles. Nat. Med. 16, 1035–1041 (2010).
Liu, E. et al. Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent antitumor activity. Leukemia 32, 520–531 (2018).
Yu, L. Y. et al. Promoting the activation of T cells with glycopolymer-modified dendritic cells by enhancing cell interactions. Sci. Adv. 6, eabb6595 (2020).
Shields, C. W. et al. Cellular backpacks for macrophage immunotherapy. Sci. Adv. 6, eaaz6579 (2020).
Lee, D. Y. et al. Cell surface engineering and application in cell delivery to heart diseases. J. Biol. Eng. 12, 28 (2018).
Park, J. et al. Engineering the surface of therapeutic “living” cells. Chem. Rev. 118, 1664–1690 (2018).
Yan, J., Yu, J., Wang, C. & Gu, Z. Red blood cells for drug delivery. Small Methods 1, 1700270 (2017).
Villa, C. H., Anselmo, A. C., Mitragotri, S. & Muzykantov, V. Red blood cells: supercarriers for drugs, biologicals, and nanoparticles and inspiration for advanced delivery systems. Adv. Drug Deliv. Rev. 106, 88–103 (2016).
Semple, J. W., Italiano, J. E. Jr & Freedman, J. Platelets and the immune continuum. Nat. Rev. Immunol. 11, 264–274 (2011).
Sørensen, A. L. et al. Role of sialic acid for platelet life span: exposure of β-galactose results in the rapid clearance of platelets from the circulation by asialoglycoprotein receptor-expressing liver macrophages and hepatocytes. Blood 114, 1645–1654 (2009).
Ihler, G. M., Glew, R. H. & Schnure, F. W. Enzyme loading of erythrocytes. Proc. Natl Acad. Sci. USA 70, 2663–2666 (1973).
Pishesha, N. et al. Engineered erythrocytes covalently linked to antigenic peptides can protect against autoimmune disease. Proc. Natl Acad. Sci. USA 114, 3157–3162 (2017).
Morera, D. & MacKenzie, S. A. Is there a direct role for erythrocytes in the immune response? Vet. Res. 42, 89 (2011).
Chambers, E. & Mitragotri, S. Prolonged circulation of large polymeric nanoparticles by non-covalent adsorption on erythrocytes. J. Control. Release 100, 111–119 (2004).
Glassman, P. M. et al. Vascular drug delivery using carrier red blood cells: focus on RBC surface loading and pharmacokinetics. Pharmaceutics 12, 440 (2020).
Wang, C. et al. In situ activation of platelets with checkpoint inhibitors for post-surgical cancer immunotherapy. Nat. Biomed. Eng. 1, 0011 (2017).
Patel, A. A. et al. The fate and lifespan of human monocyte subsets in steady state and systemic inflammation. J. Exp. Med. 214, 1913–1923 (2017).
Yona, S. et al. Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity 38, 79–91 (2013).
Liang, T. et al. Recent advances in macrophage-mediated drug delivery systems. Int. J. Nanomed. 16, 2703–2714 (2021).
Arvanitis, C. D., Ferraro, G. B. & Jain, R. K. The blood–brain barrier and blood–tumour barrier in brain tumours and metastases. Nat. Rev. Cancer 20, 26–41 (2020).
Nance, E., Pun, S. H., Saigal, R. & Sellers, D. L. Drug delivery to the central nervous system. Nat. Rev. Mater. 7, 314–331 (2022).
Van Tellingen, O. et al. Overcoming the blood–brain tumor barrier for effective glioblastoma treatment. Drug Resist. Update 19, 1–12 (2015).
Mu, C. F. et al. Targeted drug delivery for tumor therapy inside the bone marrow. Biomaterials 155, 191–202 (2018).
Ley, K., Laudanna, C., Cybulsky, M. I. & Nourshargh, S. Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat. Rev. Immunol. 7, 678–689 (2007).
Liu, L. et al. From blood to the brain: can systemically transplanted mesenchymal stem cells cross the blood–brain barrier? Stem Cells Int. 2013, 435093 (2013).
Ratnam, N. M., Gilbert, M. R. & Giles, A. J. Immunotherapy in CNS cancers: the role of immune cell trafficking. Neuro Oncol 21, 37–46 (2019).
Stuckey, D. W. & Shah, K. Stem cell-based therapies for cancer treatment: separating hope from hype. Nat. Rev. Cancer 14, 683–691 (2014).
Mooney, R., Hammad, M., Batalla-Covello, J., Abdul Majid, A. & Aboody, K. S. Concise review: neural stem cell-mediated targeted cancer therapies. Stem Cells Transl. Med. 7, 740–747 (2018).
Luo, Z. et al. Neutrophil hitchhiking for drug delivery to the bone marrow. Nat. Nanotechnol. 18, 647–656 (2023).
Van Apeldoorn, A. A. et al. Raman imaging of PLGA microsphere degradation inside macrophages. J. Am. Chem. Soc. 126, 13226–13227 (2004).
Champion, J. A. & Mitragotri, S. Role of target geometry in phagocytosis. Proc. Natl Acad. Sci. USA 103, 4930–4934 (2006).
Gilbert, J. B., O’Brien, J. S., Suresh, H. S., Cohen, R. E. & Rubner, M. F. Orientation-specific attachment of polymeric microtubes on cell surfaces. Adv. Mater. 25, 5948–5952 (2013).
Sharma, G. et al. Polymer particle shape independently influences binding and internalization by macrophages. J. Control. Release 147, 408–412 (2010).
SenGupta, S., Parent, C. A. & Bear, J. E. The principles of directed cell migration. Nat. Rev. Mol. Cell Biol. 22, 529–547 (2021).
Ukidve, A. et al. Erythrocyte-driven immunization via biomimicry of their natural antigen-presenting function. Proc. Natl Acad. Sci. USA 117, 17727–17736 (2020).
Sackstein, R. et al. Ex vivo glycan engineering of CD44 programs human multipotent mesenchymal stromal cell trafficking to bone. Nat. Med. 14, 181–187 (2008).
Ullah, M., Liu, D. D. & Thakor, A. S. Mesenchymal stromal cell homing: mechanisms and strategies for improvement. iScience 15, 421–438 (2019).
Tang, J. et al. Targeted repair of heart injury by stem cells fused with platelet nanovesicles. Nat. Biomed. Eng. 2, 17–26 (2018).
Lv, Y. et al. Near-infrared light-triggered platelet arsenal for combined photothermal-immunotherapy against cancer. Sci. Adv. 7, eabd7614 (2021).
Ho-Tin-Noe, B., Boulaftali, Y. & Camerer, E. Platelets and vascular integrity: how platelets prevent bleeding in inflammation. Blood 131, 277–288 (2018).
Rao, L. et al. Platelet-facilitated photothermal therapy of head and neck squamous cell carcinoma. Angew. Chem. Int. Ed. 57, 986–991 (2018).
Moser, B. & Loetscher, P. Lymphocyte traffic control by chemokines. Nat. Immunol. 2, 123–128 (2001).
Schenkel, A. R., Mamdouh, Z. & Muller, W. A. Locomotion of monocytes on endothelium is a critical step during extravasation. Nat. Immunol. 5, 393–400 (2004).
Shi, C. & Pamer, E. G. Monocyte recruitment during infection and inflammation. Nat. Rev. Immunol. 11, 762–774 (2011).
Burn, G. L., Foti, A., Marsman, G., Patel, D. F. & Zychlinsky, A. The neutrophil. Immunity 54, 1377–1391 (2021).
Anselmo, A. C. et al. Monocyte-mediated delivery of polymeric backpacks to inflamed tissues: a generalized strategy to deliver drugs to treat inflammation. J. Control. Release 199, 29–36 (2015).
Palucka, K. & Banchereau, J. Dendritic-cell-based therapeutic cancer vaccines. Immunity 39, 38–48 (2013).
Kasinskas, R. W. & Forbes, N. S. Salmonella typhimurium lacking ribose chemoreceptors localize in tumor quiescence and induce apoptosis. Cancer Res. 67, 3201–3209 (2007).
Zhou, S., Gravekamp, C., Bermudes, D. & Liu, K. Tumour-targeting bacteria engineered to fight cancer. Nat. Rev. Cancer 18, 727–743 (2018).
Suh, S. et al. Nanoscale bacteria‐enabled autonomous drug delivery system (NanoBEADS) enhances intratumoral transport of nanomedicine. Adv. Sci. 6, 1801309 (2019).
Chen, W. et al. Bacteria-driven hypoxia targeting for combined biotherapy and photothermal therapy. ACS Nano 12, 5995–6005 (2018).
Park, B.-W., Zhuang, J., Yasa, O. & Sitti, M. Multifunctional bacteria-driven microswimmers for targeted active drug delivery. ACS Nano 11, 8910–8923 (2017).
Naik, S., Larsen, S. B., Cowley, C. J. & Fuchs, E. Two to tango: dialog between immunity and stem cells in health and disease. Cell 175, 908–920 (2018).
Haider, H., Jiang, S., Idris, N. M. & Ashraf, M. IGF-1-overexpressing mesenchymal stem cells accelerate bone marrow stem cell mobilization via paracrine activation of SDF-1α/CXCR4 signaling to promote myocardial repair. Circ. Res. 103, 1300–1308 (2008).
Stappenbeck, T. S. & Miyoshi, H. The role of stromal stem cells in tissue regeneration and wound repair. Science 324, 1666–1669 (2009).
Leong, J. et al. Surface tethering of inflammation-modulatory nanostimulators to stem cells for ischemic muscle repair. ACS Nano 14, 5298–5313 (2020).
Waldman, A. D., Fritz, J. M. & Lenardo, M. J. A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nat. Rev. Immunol. 20, 651–668 (2020).
Zucchini, N. et al. Natural killer cells in immunodefense against infective agents. Expert Rev. Anti Infect. Ther. 6, 867–885 (2008).
Myers, J. A. & Miller, J. S. Exploring the NK cell platform for cancer immunotherapy. Nat. Rev. Clin. Oncol. 18, 85–100 (2021).
Bald, T., Krummel, M. F., Smyth, M. J. & Barry, K. C. The NK cell-cancer cycle: advances and new challenges in NK cell-based immunotherapies. Nat. Immunol. 21, 835–847 (2020).
Liu, S. et al. NK cell-based cancer immunotherapy: from basic biology to clinical development. J. Hematol. Oncol. 14, 7 (2021).
Vivier, E., Tomasello, E., Baratin, M., Walzer, T. & Ugolini, S. Functions of natural killer cells. Nat. Immunol. 9, 503–510 (2008).
Eskandari, S. K. et al. Regulatory T cells engineered with TCR signaling-responsive IL-2 nanogels suppress alloimmunity in sites of antigen encounter. Sci. Transl. Med. 12, eaaw4744 (2020).
Roncarolo, M. G. & Battaglia, M. Regulatory T-cell immunotherapy for tolerance to self antigens and alloantigens in humans. Nat. Rev. Immunol. 7, 585–598 (2007).
Chen, Q. et al. In situ sprayed bioresponsive immunotherapeutic gel for post-surgical cancer treatment. Nat. Nanotechnol. 14, 89–97 (2019).
Wang, C. et al. Oncolytic mineralized bacteria as potent locally administered immunotherapeutics. Nat. Biomed. Eng. https://doi.org/10.1038/s41551-024-01191-w (2024).
Lou, X., Chen, Z., He, Z., Sun, M. & Sun, J. Bacteria-mediated synergistic cancer therapy: small microbiome has a big hope. Nanomicro. Lett. 13, 37 (2021).
Zheng, J. H. et al. Two-step enhanced cancer immunotherapy with engineered Salmonella typhimurium secreting heterologous flagellin. Sci. Transl. Med. 9, eaak9537 (2017).
Sieow, B. F., Wun, K. S., Yong, W. P., Hwang, I. Y. & Chang, M. W. Tweak to treat: reprograming bacteria for cancer treatment. Trends Cancer 7, 447–464 (2021).
Saccheri, F. et al. Bacteria-induced gap junctions in tumors favor antigen cross-presentation and antitumor immunity. Sci. Transl. Med. 2, 44ra57 (2010).
Custodio, C. A. & Mano, J. F. Cell surface engineering to control cellular interactions. ChemNanoMat 2, 376–384 (2016).
Simons, K. & Sampaio, J. L. Membrane organization and lipid rafts. Cold Spring Harb. Perspect. Biol. 3, a004697 (2011).
Mager, M. D., LaPointe, V. & Stevens, M. M. Exploring and exploiting chemistry at the cell surface. Nat. Chem. 3, 582–589 (2011).
Bertozzi, C. R. & Kiessling, L. L. Chemical glycobiology. Science 291, 2357–2364 (2001).
Lee, D. Y., Park, S. J., Nam, J. H. & Byun, Y. A new strategy toward improving immunoprotection in cell therapy for diabetes mellitus: long-functioning PEGylated islets in vivo. Tissue Eng. 12, 615–623 (2006).
Rossi, N. A. et al. Red blood cell membrane grafting of multi-functional hyperbranched polyglycerols. Biomaterials 31, 4167–4178 (2010).
Chapanian, R. et al. Therapeutic cells via functional modification: influence of molecular properties of polymer grafts on in vivo circulation, clearance, immunogenicity, and antigen protection. Biomacromolecules 14, 2052–2062 (2013).
Bradley, A. J., Murad, K. L., Regan, K. L. & Scott, M. D. Biophysical consequences of linker chemistry and polymer size on stealth erythrocytes: size does matter. Biochim. Biophys. Acta 1561, 147–158 (2002).
Scott, M. D., Murad, K. L., Koumpouras, F., Talbot, M. & Eaton, J. W. Chemical camouflage of antigenic determinants: stealth erythrocytes. Proc. Natl Acad. Sci. USA 94, 7566–7571 (1997).
Rhodes, J. et al. Therapeutic potentiation of the immune system by costimulatory Schiff-base-forming drugs. Nature 377, 71–75 (1995).
Kim, H. et al. General and facile coating of single cells via mild reduction. J. Am. Chem. Soc. 140, 1199–1202 (2018).
Sugimoto, S., Moriyama, R., Mori, T. & Iwasaki, Y. Surface engineering of macrophages with nucleic acid aptamers for the capture of circulating tumor cells. Chem. Commun. 51, 17428–17430 (2015).
Hoyle, C. E., Lowe, A. B. & Bowman, C. N. Thiol-click chemistry: a multifaceted toolbox for small molecule and polymer synthesis. Chem. Soc. Rev. 39, 1355–1387 (2010).
Wayteck, L. et al. Hitchhiking nanoparticles: reversible coupling of lipid-based nanoparticles to cytotoxic T lymphocytes. Biomaterials 77, 243–254 (2016).
Geng, W. et al. Click reaction for reversible encapsulation of single yeast cells. ACS Nano 13, 14459–14467 (2019).
Ulrich, S., Boturyn, D., Marra, A., Renaudet, O. & Dumy, P. Oxime ligation: a chemoselective click-type reaction for accessing multifunctional biomolecular constructs. Chemistry 20, 34–41 (2014).
Dutta, D., Pulsipher, A., Luo, W. & Yousaf, M. N. Synthetic chemoselective rewiring of cell surfaces: generation of three-dimensional tissue structures. J. Am. Chem. Soc. 133, 8704–8713 (2011).
Dutta, D., Pulsipher, A., Luo, W., Mak, H. & Yousaf, M. N. Engineering cell surfaces via liposome fusion. Bioconjug. Chem. 22, 2423–2433 (2011).
Rogozhnikov, D., O’Brien, P. J., Elahipanah, S. & Yousaf, M. N. Scaffold free bio-orthogonal assembly of 3-dimensional cardiac tissue via cell surface engineering. Sci. Rep. 6, 39806 (2016).
Kayser, H. et al. Biosynthesis of a nonphysiological sialic acid in different rat organs, using N-propanoyl-d-hexosamines as precursors. J. Biol. Chem. 267, 16934–16938 (1992).
Wang, H. & Mooney, D. J. Metabolic glycan labelling for cancer-targeted therapy. Nat. Chem. 12, 1102–1114 (2020).
Wang, H. et al. Metabolic labeling and targeted modulation of dendritic cells. Nat. Mater. 19, 1244–1252 (2020).
Hu, Q. et al. Conjugation of haematopoietic stem cells and platelets decorated with anti-PD-1 antibodies augments anti-leukaemia efficacy. Nat. Biomed. Eng. 2, 831–840 (2018).
Popp, M. W., Antos, J. M., Grotenbreg, G. M., Spooner, E. & Ploegh, H. L. Sortagging: a versatile method for protein labeling. Nat. Chem. Biol. 3, 707–708 (2007).
Shi, J. et al. Engineered red blood cells as carriers for systemic delivery of a wide array of functional probes. Proc. Natl Acad. Sci. USA 111, 10131–10136 (2014).
Chen, I., Howarth, M., Lin, W. Y. & Ting, A. Y. Site-specific labeling of cell surface proteins with biophysical probes using biotin ligase. Nat. Methods 2, 99–104 (2005).
Lin, C. W. & Ting, A. Y. Transglutaminase-catalyzed site-specific conjugation of small-molecule probes to proteins in vitro and on the surface of living cells. J. Am. Chem. Soc. 128, 4542–4543 (2006).
Qi, C. et al. TGase-mediated cell membrane modification and targeted cell delivery to inflammatory endothelium. Biomaterials 269, 120276 (2021).
Pulsipher, A., Griffin, M. E., Stone, S. E. & Hsieh-Wilson, L. C. Long-lived engineering of glycans to direct stem cell fate. Angew. Chem. Int. Ed. 54, 1466–1470 (2015).
De Oliveira, S. & Saldanha, C. An overview about erythrocyte membrane. Clin. Hemorheol. Microcirc. 44, 63–74 (2010).
Wilson, J. T., Krishnamurthy, V. R., Cui, W. X., Qu, Z. & Chaikof, E. L. Noncovalent cell surface engineering with cationic graft copolymers. J. Am. Chem. Soc. 131, 18228–18229 (2009).
Gribova, V., Auzely-Velty, R. & Picart, C. Polyelectrolyte multilayer assemblies on materials surfaces: from cell adhesion to tissue engineering. Chem. Mater. 24, 854–869 (2012).
Germain, M. et al. Protection of mammalian cell used in biosensors by coating with a polyelectrolyte shell. Biosens. Bioelectron. 21, 1566–1573 (2006).
Zelepukin, I. V. et al. Nanoparticle-based drug delivery via RBC-hitchhiking for the inhibition of lung metastases growth. Nanoscale 11, 1636–1646 (2019).
Zhao, Z. et al. Engineering of living cells with polyphenol-functionalized biologically active nanocomplexes. Adv. Mater. 32, e2003492 (2020).
Wang, C. et al. Red blood cells for glucose-responsive insulin delivery. Adv. Mater. 29, 1606617 (2017).
Wang, J. Q. et al. Glucose transporter inhibitor-conjugated insulin mitigates hypoglycemia. Proc. Natl Acad. Sci. USA 116, 10744–10748 (2019).
Livnah, O., Bayer, E. A., Wilchek, M. & Sussman, J. L. Three-dimensional structures of avidin and the avidin–biotin complex. Proc. Natl Acad. Sci. USA 90, 5076–5080 (1993).
Muzykantov, V. R., Smirnov, M. D. & Samokhin, G. P. Avidin attachment to biotinylated erythrocytes induces homologous lysis via the alternative pathway of complement. Blood 78, 2611–2618 (1991).
Murciano, J. C. et al. Prophylactic fibrinolysis through selective dissolution of nascent clots by tPA-carrying erythrocytes. Nat. Biotechnol. 21, 891–896 (2003).
Cheng, H. et al. Nanoparticulate cellular patches for cell-mediated tumoritropic delivery. ACS Nano 4, 625–631 (2010).
Klyachko, N. L. et al. Macrophages with cellular backpacks for targeted drug delivery to the brain. Biomaterials 140, 79–87 (2017).
Polak, R. et al. Liposome-loaded cell backpacks. Adv. Healthc. Mater. 4, 2832–2841 (2015).
Chandrasekaran, S., Chan, M. F., Li, J. & King, M. R. Super natural killer cells that target metastases in the tumor draining lymph nodes. Biomaterials 77, 66–76 (2016).
Zaitsev, S. et al. Human complement receptor type 1-directed loading of tissue plasminogen activator on circulating erythrocytes for prophylactic fibrinolysis. Blood 108, 1895–1902 (2006).
Gao, C. et al. Bioorthogonal supramolecular cell-conjugation for targeted hitchhiking drug delivery. Mater. Today 40, 9–17 (2020).
Cao, H. et al. Bioengineered macrophages can responsively transform into nanovesicles to target lung metastasis. Nano Lett. 18, 4762–4770 (2018).
Chung, H. A., Kato, K., Itoh, C., Ohhashi, S. & Nagamune, T. Casual cell surface remodeling using biocompatible lipid-poly(ethylene glycol)(n): development of stealth cells and monitoring of cell membrane behavior in serum-supplemented conditions. J. Biomed. Mater. Res. 70, 179–185 (2004).
Armstrong, J. P. K. et al. Artificial membrane-binding proteins stimulate oxygenation of stem cells during engineering of large cartilage tissue. Nat. Commun. 6, 7405 (2015).
Jeong, J. H. et al. Leukocyte-mimicking stem cell delivery via in situ coating of cells with a bioactive hyperbranched polyglycerol. J. Am. Chem. Soc. 135, 8770–8773 (2013).
Yamamoto, T., Teramura, Y., Itagaki, T., Arima, Y. & Iwata, H. Interaction of poly(ethylene glycol)-conjugated phospholipids with supported lipid membranes and their influence on protein adsorption. Sci. Technol. Adv. Mater. 17, 677–684 (2016).
Church, D. C. & Pokorski, J. K. Cell engineering with functional poly(oxanorbornene) block copolymers. Angew. Chem. Int. Ed. 59, 11379–11383 (2020).
Lostalé-Seijo, I. & Montenegro, J. Synthetic materials at the forefront of gene delivery. Nat. Rev. Chem. 2, 258–277 (2018).
Bulcha, J. T., Wang, Y., Ma, H., Tai, P. W. L. & Gao, G. Viral vector platforms within the gene therapy landscape. Signal Transduct. Target. Ther. 6, 53 (2021).
Day, J. W. et al. Onasemnogene abeparvovec gene therapy for symptomatic infantile-onset spinal muscular atrophy in patients with two copies of SMN2 (STR1VE): an open-label, single-arm, multicentre, phase 3 trial. Lancet Neurol. 20, 284–293 (2021).
Wang, D., Tai, P. W. L. & Gao, G. Adeno-associated virus vector as a platform for gene therapy delivery. Nat. Rev. Drug Discov. 18, 358–378 (2019).
Yin, H. et al. Non-viral vectors for gene-based therapy. Nat. Rev. Genet. 15, 541–555 (2014).
Liu, X. et al. Fusogenic reactive oxygen species triggered charge-reversal vector for effective gene delivery. Adv. Mater. 28, 1743–1752 (2016).
Green, J. J. et al. Nanoparticles for gene transfer to human embryonic stem cell colonies. Nano Lett. 8, 3126–3130 (2008).
Peister, A., Mellad, J. A., Wang, M., Tucker, H. A. & Prockop, D. J. Stable transfection of MSCs by electroporation. Gene Ther. 11, 224–228 (2004).
Gornalusse, G. G. et al. HLA-E-expressing pluripotent stem cells escape allogeneic responses and lysis by NK cells. Nat. Biotechnol. 35, 765–772 (2017).
Zhao, L., Teklemariam, T. & Hantash, B. M. Heterelogous expression of mutated HLA-G decreases immunogenicity of human embryonic stem cells and their epidermal derivatives. Stem Cell Res. 13, 342–354 (2014).
Deuse, T. et al. Hypoimmunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients. Nat. Biotechnol. 37, 252–258 (2019).
Rong, Z. et al. An effective approach to prevent immune rejection of human ESC-derived allografts. Cell Stem Cell 14, 121–130 (2014).
Ben Nasr, M. et al. PD-L1 genetic overexpression or pharmacological restoration in hematopoietic stem and progenitor cells reverses autoimmune diabetes. Sci. Transl. Med. 9, eaam7543 (2017).
Zhang, X. et al. Engineered PD-L1-expressing platelets reverse new-onset type 1 diabetes. Adv. Mater. 32, 1907692 (2020).
Dimitrov, A. S. (ed.) Therapeutic Antibodies: Methods and Protocols (Humana, 2009).
Kochenderfer, J. N. et al. Construction and preclinical evaluation of an anti-CD19 chimeric antigen receptor. J. Immunother. 32, 689–702 (2009).
Wolf, P., Alzubi, J., Gratzke, C. & Cathomen, T. The potential of CAR T cell therapy for prostate cancer. Nat. Rev. Urol. 18, 556–571 (2021).
Li, J., Sharkey, C. C., Wun, B., Liesveld, J. L. & King, M. R. Genetic engineering of platelets to neutralize circulating tumor cells. J. Control. Release 228, 38–47 (2016).
Chrousos, G. P. Stress and disorders of the stress system. Nat. Rev. Endocrinol. 5, 374–381 (2009).
Chavez, J. C., Bachmeier, C. & Kharfan-Dabaja, M. A. CAR T-cell therapy for B-cell lymphomas: clinical trial results of available products. Ther. Adv. Hematol. 10, 2040620719841581 (2019).
Raje, N. et al. Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma. N. Engl. J. Med. 380, 1726–1737 (2019).
Ali, M. et al. T cells targeted to TdT kill leukemic lymphoblasts while sparing normal lymphocytes. Nat. Biotechnol. 40, 488–498 (2022).
Siriwon, N. et al. CAR-T cells surface-engineered with drug-encapsulated nanoparticles can ameliorate intratumoral T-cell hypofunction. Cancer Immunol. Res. 6, 812–824 (2018).
Stephan, M. T., Stephan, S. B., Bak, P., Chen, J. & Irvine, D. J. Synapse-directed delivery of immunomodulators using T-cell-conjugated nanoparticles. Biomaterials 33, 5776–5787 (2012).
Hao, M. X. et al. Combination of metabolic intervention and T cell therapy enhances solid tumor immunotherapy. Sci. Transl. Med. 12, eaaz6667 (2020).
Xie, Y. Q. et al. Redox-responsive interleukin-2 nanogel specifically and safely promotes the proliferation and memory precursor differentiation of tumor-reactive T-cells. Biomater. Sci. 7, 1345–1357 (2019).
Li, J., Jiang, X., Li, H., Gelinsky, M. & Gu, Z. Tailoring materials for modulation of macrophage fate. Adv. Mater. 33, 2004172 (2021).
Xia, Y. et al. Engineering macrophages for cancer immunotherapy and drug delivery. Adv. Mater. 32, 2002054 (2020).
Baer, C. et al. Suppression of microRNA activity amplifies IFN-γ-induced macrophage activation and promotes anti-tumour immunity. Nat. Cell Biol. 18, 790–802 (2016).
Brown, J. M., Recht, L. & Strober, S. The promise of targeting macrophages in cancer therapy. Clin. Cancer Res. 23, 3241–3250 (2017).
Klei, T. R. L. et al. Hemolysis in the spleen drives erythrocyte turnover. Blood 136, 1579–1589 (2020).
Zhao, Z. M., Ukidve, A., Gao, Y. S., Kim, J. & Mitragotri, S. Erythrocyte leveraged chemotherapy (ELeCt): nanoparticle assembly on erythrocyte surface to combat lung metastasis. Sci. Adv. 5, eaax9250 (2019).
Zhao, Z. M. et al. Systemic tumour suppression via the preferential accumulation of erythrocyte-anchored chemokine-encapsulating nanoparticles in lung metastases. Nat. Biomed. Eng. 5, 441–454 (2021).
Yang, Y. et al. T cell-mimicking platelet–drug conjugates. Matter 6, 2340–2355 (2023).
Quispe-Tintaya, W. et al. Nontoxic radioactive Listeriaat is a highly effective therapy against metastatic pancreatic cancer. Proc. Natl Acad. Sci. USA 110, 8668–8673 (2013).
Luo, C. H., Huang, C. T., Su, C. H. & Yeh, C. S. Bacteria-mediated hypoxia-specific delivery of nanoparticles for tumors imaging and therapy. Nano Lett. 16, 3493–3499 (2016).
Felfoul, O. et al. Magneto-aerotactic bacteria deliver drug-containing nanoliposomes to tumour hypoxic regions. Nat. Nanotechnol. 11, 941–947 (2016).
Fan, J. X. et al. Engineered bacterial bioreactor for tumor therapy via Fenton-like reaction with localized H2O2 generation. Adv. Mater. 31, 1808278 (2019).
Rafiq, S. et al. Targeted delivery of a PD-1-blocking scFv by CAR-T cells enhances anti-tumor efficacy in vivo. Nat. Biotechnol. 36, 847–856 (2018).
Topalian, S. L., Taube, J. M. & Pardoll, D. M. Neoadjuvant checkpoint blockade for cancer immunotherapy. Science 367, eaax0182 (2020).
Powles, T. et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature 515, 558–562 (2014).
Casey, S. C. et al. MYC regulates the antitumor immune response through CD47 and PD-L1. Science 352, 227–231 (2016).
Chen, Q., Wang, C., Chen, G., Hu, Q. & Gu, Z. Delivery strategies for immune checkpoint blockade. Adv. Healthc. Mater. 7, e1800424 (2018).
Liu, X., Wang, D., Zhang, P. & Li, Y. Recent advances in nanosized drug delivery systems for overcoming the barriers to anti-PD immunotherapy of cancer. Nano Today 29, 100801 (2019).
Bambace, N. M. & Holmes, C. E. The platelet contribution to cancer progression. J. Thromb. Haemost. 9, 237–249 (2011).
Yu, L. X. et al. Platelets promote tumour metastasis via interaction between TLR4 and tumour cell-released high-mobility group box1 protein. Nat. Commun. 5, 5256 (2014).
Placke, T. et al. Platelet-derived MHC class I confers a pseudonormal phenotype to cancer cells that subverts the antitumor reactivity of natural killer immune cells. Cancer Res. 72, 440–448 (2012).
Hu, Q. et al. Inhibition of post-surgery tumour recurrence via a hydrogel releasing CAR-T cells and anti-PDL1-conjugated platelets. Nat. Biomed. Eng. 5, 1038–1047 (2021).
Li, H. et al. Disrupting tumour vasculature and recruitment of aPDL1-loaded platelets control tumour metastasis. Nat. Commun. 12, 2773 (2021).
Zhang, X. et al. Engineering PD-1-presenting platelets for cancer immunotherapy. Nano Lett. 18, 5716–5725 (2018).
Huang, B. N. et al. Active targeting of chemotherapy to disseminated tumors using nanoparticle-carrying T cells. Sci. Transl. Med. 7, 291ra94 (2015).
Im, S. et al. Harnessing the formation of natural killer–tumor cell immunological synapses for enhanced therapeutic effect in solid tumors. Adv. Mater. 32, 2000020 (2020).
Siegler, E. L. et al. Combination cancer therapy using chimeric antigen receptor-engineered natural killer cells as drug carriers. Mol. Ther. 25, 2607–2619 (2017).
Chandrasekaran, S., McGuire, M. J. & King, M. R. Sweeping lymph node micrometastases off their feet: an engineered model to evaluate natural killer cell mediated therapeutic intervention of circulating tumor cells that disseminate to the lymph nodes. Lab Chip 14, 118–127 (2014).
Reyes, A., Mohanty, A., Pharaon, R. & Massarelli, E. Association between immunosuppressive therapy utilized in the treatment of autoimmune disease or transplant and cancer progression. Biomedicines 11, 99 (2023).
Desai, R. J. et al. Risk of serious infections associated with use of immunosuppressive agents in pregnant women with autoimmune inflammatory conditions: cohort study. Br. Med. J. 356, j895 (2017).
Miller, S. D., Turley, D. M. & Podojil, J. R. Antigen-specific tolerance strategies for the prevention and treatment of autoimmune disease. Nat. Rev. Immunol. 7, 665–677 (2007).
Neumann, C. et al. c-Maf-dependent Treg cell control of intestinal TH17 cells and IgA establishes host–microbiota homeostasis. Nat. Immunol. 20, 471–481 (2019).
Schorer, M. et al. Rapid expansion of Treg cells protects from collateral colitis following a viral trigger. Nat. Commun. 11, 1522 (2020).
Vignali, D. A., Collison, L. W. & Workman, C. J. How regulatory T cells work. Nat. Rev. Immunol. 8, 523–532 (2008).
Akbarpour, M. et al. Insulin B chain 9-23 gene transfer to hepatocytes protects from type 1 diabetes by inducing Ag-specific FoxP3+ Tregs. Sci. Transl. Med. 7, 289ra81 (2015).
Bluestone, J. A. et al. Type 1 diabetes immunotherapy using polyclonal regulatory T cells. Sci. Transl. Med. 7, 315ra189 (2015).
Sun, C., Mezzadra, R. & Schumacher, T. N. Regulation and function of the PD-L1 checkpoint. Immunity 48, 434–452 (2018).
Braleymullen, H., Tompson, J. G., Sharp, G. C. & Kyriakos, M. Suppression of experimental autoimmune thyroiditis in guinea pigs by pretreatment with thyroglobulin-coupled spleen cells. Cell. Immunol. 51, 408–413 (1980).
Fife, B. T. et al. Insulin-induced remission in new-onset NOD mice is maintained by the PD-1–PD-L1 pathway. J. Exp. Med. 203, 2737–2747 (2006).
Kontos, S., Kourtis, I. C., Dane, K. Y. & Hubbell, J. A. Engineering antigens for in situ erythrocyte binding induces T-cell deletion. Proc. Natl Acad. Sci. USA 110, E60–E68 (2013).
Lorentz, K. M., Kontos, S., Diaceri, G., Henry, H. & Hubbell, J. A. Engineered binding to erythrocytes induces immunological tolerance to E. coli asparaginase. Sci. Adv. 1, e1500112 (2015).
Lutterotti, A. et al. Antigen-specific tolerance by autologous myelin peptide-coupled cells: a phase 1 trial in multiple sclerosis. Sci. Transl. Med. 5, 188ra75 (2013).
Chovatiya, R. & Medzhitov, R. Stress, inflammation, and defense of homeostasis. Mol. Cell 54, 281–288 (2014).
Newton, K., Dixit, V. M. & Kayagaki, N. Dying cells fan the flames of inflammation. Science 374, 1076–1080 (2021).
Medzhitov, R. The spectrum of inflammatory responses. Science 374, 1070–1075 (2021).
Ma, Q. et al. Calming cytokine storm in pneumonia by targeted delivery of TPCA-1 using platelet-derived extracellular vesicles. Matter 3, 287–301 (2020).
Martinez, J. O. et al. Mesenchymal stromal cell‐mediated treatment of local and systemic inflammation through the triggering of an anti‐inflammatory response. Adv. Funct. Mater. 31, 2002997 (2020).
Smith, W. J. et al. Cell-mediated assembly of phototherapeutics. Angew. Chem. Int. Ed. 53, 10945–10948 (2014).
Brenner, J. S. et al. Red blood cell-hitchhiking boosts delivery of nanocarriers to chosen organs by orders of magnitude. Nat. Commun. 9, 2684 (2018).
Adeoye, O. & Broderick, J. P. Advances in the management of intracerebral hemorrhage. Nat. Rev. Neurol. 6, 593–601 (2010).
Hou, J. et al. Accessing neuroinflammation sites: monocyte/neutrophil-mediated drug delivery for cerebral ischemia. Sci. Adv. 5, eaau8301 (2019).
Li, Y. et al. Ultrasound controlled anti-inflammatory polarization of platelet decorated microglia for targeted ischemic stroke therapy. Angew. Chem. Int. Ed. 60, 5083–5090 (2021).
Xu, X. et al. Self-regulated hirudin delivery for anticoagulant therapy. Sci. Adv. 6, eabc0382 (2020).
Mackman, N. Triggers, targets and treatments for thrombosis. Nature 451, 914–918 (2008).
Mackman, N., Bergmeier, W., Stouffer, G. A. & Weitz, J. I. Therapeutic strategies for thrombosis: new targets and approaches. Nat. Rev. Drug Discov. 19, 333–352 (2020).
Pisapia, J. M. et al. Microthrombosis after experimental subarachnoid hemorrhage: time course and effect of red blood cell-bound thrombin-activated pro-urokinase and clazosentan. Exp. Neurol. 233, 357–363 (2012).
Li, Z. et al. Cell‐based delivery systems: emerging carriers for immunotherapy. Adv. Funct. Mater. 31, 2100088 (2021).
Santander, A. M. et al. Paracrine interactions between adipocytes and tumor cells recruit and modify macrophages to the mammary tumor microenvironment: the role of obesity and inflammation in breast adipose tissue. Cancers 7, 143–178 (2015).
Zhang, M. et al. Adipocyte-derived lipids mediate melanoma progression via FATP proteins. Cancer Discov. 8, 1006–1025 (2018).
Nieman, K. M. et al. Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat. Med. 17, 1498–1503 (2011).
Wen, D. et al. Adipocytes as anticancer drug delivery depot. Matter 1, 1203–1214 (2019).
Ceballos Bolaños, C. et al. Optimization of a universal allogeneic CAR-T cells combining CRISPR and transposon-based technologies for treatment of acute myeloid leukemia. Blood 142, 3457 (2023).
McGuirk, J. et al. A phase 1 dose escalation and cohort expansion study of the safety and efficacy of allogeneic CRISPR–Cas9-engineered T cells (CTX110) in patients (Pts) with relapsed or refractory (R/R) B-cell malignancies (CARBON). J. Clin. Oncol. 39, TPS7570 (2021).
Mao, A. S. et al. Programmable microencapsulation for enhanced mesenchymal stem cell persistence and immunomodulation. Proc. Natl Acad. Sci. USA 116, 15392–15397 (2019).
Feng, M. et al. Phagocytosis checkpoints as new targets for cancer immunotherapy. Nat. Rev. Cancer 19, 568–586 (2019).
Lakhanpal, G. K. et al. The inositol phosphatase SHIP-1 is negatively regulated by Fli-1 and its loss accelerates leukemogenesis. Blood 116, 428–436 (2010).
Zou, S. et al. Targeting STAT3 in cancer immunotherapy. Mol. Cancer 19, 145 (2020).
Tap, W. D. et al. Pexidartinib versus placebo for advanced tenosynovial giant cell tumour (ENLIVEN): a randomised phase 3 trial. Lancet 394, 478–487 (2019).
Ramesh, A., Kumar, S., Nandi, D. & Kulkarni, A. CSF1R- and SHP2-inhibitor-loaded nanoparticles enhance cytotoxic activity and phagocytosis in tumor-associated macrophages. Adv. Mater. 31, e1904364 (2019).
Helfinger, V. et al. Genetic deletion of Nox4 enhances cancerogen-induced formation of solid tumors. Proc. Natl Acad. Sci. USA 118, e2020152118 (2021).
De Henau, O. et al. Overcoming resistance to checkpoint blockade therapy by targeting PI3Kγ in myeloid cells. Nature 539, 443–447 (2016).
Ceylan, H., Giltinan, J., Kozielski, K. & Sitti, M. Mobile microrobots for bioengineering applications. Lab Chip 17, 1705–1724 (2017).
Lu, Y., Aimetti, A. A., Langer, R. & Gu, Z. Bioresponsive materials. Nat. Rev. Mater. 2, 16075 (2017).
Wen, D. et al. Engineering protein delivery depots for cancer immunotherapy. Bioconjug. Chem. 30, 515–524 (2019).
Anselmo, A. C. et al. Delivering nanoparticles to lungs while avoiding liver and spleen through adsorption on red blood cells. ACS Nano 7, 11129–11137 (2013).
Wibroe, P. P. et al. Bypassing adverse injection reactions to nanoparticles through shape modification and attachment to erythrocytes. Nat. Nanotechnol. 12, 589–594 (2017).
Liu, F. et al. Cryo-shocked tumor cells deliver CRISPR–Cas9 for lung cancer regression by synthetic lethality. Sci. Adv. 10, eadk8264 (2024).
Danielyan, K. et al. Cerebrovascular thromboprophylaxis in mice by erythrocyte-coupled tissue-type plasminogen activator. Circulation 118, 1442–1449 (2008).
Ayer, M. et al. Biotin–NeutrAvidin mediated immobilization of polymer micro- and nanoparticles on T lymphocytes. Bioconjug. Chem. 32, 541–552 (2021).
Doshi, N. et al. Cell-based drug delivery devices using phagocytosis-resistant backpacks. Adv. Mater. 23, H105–H109 (2011).
Swiston, A. J. et al. Surface functionalization of living cells with multilayer patches. Nano Lett. 8, 4446–4453 (2008).
Chang, X. et al. Monocyte-derived multipotent cell delivered programmed therapeutics to reverse idiopathic pulmonary fibrosis. Sci. Adv. 6, eaba3167 (2020).
Vickerman, B. M., O’Banion, C. P., Tan, X. & Lawrence, D. S. Light-controlled release of therapeutic proteins from red blood cells. ACS Cent. Sci. 7, 93–103 (2021).
Liu, L. et al. Nano-engineered lymphocytes for alleviating suppressive tumor immune microenvironment. Appl. Mater. Today 16, 273–279 (2019).
Zhang, L. et al. Surface‐anchored nanogel coating endows stem cells with stress resistance and reparative potency via turning down the cytokine-receptor binding pathways. Adv. Sci. 8, 2003348 (2021).
Loukogeorgakis, S. P. et al. Donor cell engineering with GSK3 inhibitor-loaded nanoparticles enhances engraftment after in utero transplantation. Blood 134, 1983–1995 (2019).
Acknowledgements
This work was supported by grants from the National Key Research and Development Program of China (2021YFA0909900), National Natural Science Foundation of China (52233013), Key Project of Science and Technology Commission of Zhejiang Province (2024C03083, 2024C03085 and 2024C03168), Zhejiang University’s start-up packages, Fundamental Research Funds for the Central Universities (2021FZZX001-46), the Starry Night Science Fund at the Shanghai Institute for Advanced Study of Zhejiang University (SN-ZJU-SIAS-009) and Juvenile Diabetes Research Foundation (grant number 2-SRA-2021-1064-M-B). A.R.K. is supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through grant KL2TR002490.
Author information
Authors and Affiliations
Contributions
Z.G., J.W. and Y.W. conceived the project. All authors contributed to writing and revising the paper and approved the final version.
Corresponding authors
Ethics declarations
Competing interests
Z.G. is the co-founder of Zenomics, Zcapsule and μZen. The other authors declare no competing interests.
Peer review
Peer review information
Nature Biomedical Engineering thanks the anonymous reviewers for their contribution to the peer review of this work.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Supplementary information
Supplementary tables and references.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Wang, Y., Shi, J., Xin, M. et al. Cell–drug conjugates. Nat. Biomed. Eng (2024). https://doi.org/10.1038/s41551-024-01230-6
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/s41551-024-01230-6
