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. 2024 Mar 11:26:101019.
doi: 10.1016/j.mtbio.2024.101019. eCollection 2024 Jun.

MRI-guided cell membrane-camouflaged bimetallic coordination nanoplatform for combined tumor phototherapy

Mengyang Zhou  1 , Yifei Wang  1 , Yaning Xia  1 , Yinhua Li  1 , Jianfeng Bao  1 , Yong Zhang  1 , Jingliang Cheng  1 , Yupeng Shi  1
Affiliations

MRI-guided cell membrane-camouflaged bimetallic coordination nanoplatform for combined tumor phototherapy

Mengyang Zhou et al. Mater Today Bio. .

Abstract

Nanotechnology for tumor diagnosis and optical therapy has attracted widespread interest due to its low toxicity and convenience but is severely limited due to uncontrollable tumor targeting. In this work, homologous cancer cell membrane-camouflaged multifunctional hybrid metal coordination nanoparticles (DRu/Gd@CM) were prepared for MRI-guided photodynamic therapy (PDT) and photothermal therapy (PTT) of tumors. Bimetallic coordination nanoparticles are composed of three functional modules: dopamine, Ru(dcbpy)3Cl2 and GdCl3, which are connected through 1,4-Bis[(1H-imidazole-1-yl)methyl]benzene (BIX). Their morphology can be easily controlled by adjusting the ratio of precursors. Optimistically, the intrinsic properties of the precursors, including the photothermal properties of polydopamine (PDA), the magnetic resonance (MR) response of Gd3+, and the singlet oxygen generation of Ru(dcbpy)3Cl2, are well preserved in the hybrid metal nanoparticles. Furthermore, the targeting of homologous cancer cell membranes enables these coordinated nanoparticles to precisely target tumor cells. The MR imaging capabilities and the combination of PDT and PTT were demonstrated in in vitro experiments. In addition, in vivo experiments indicated that the nanoplatform showed excellent tumor accumulation and therapeutic effects on mice with subcutaneous tumors, and could effectively eliminate tumors within 14 days. Therefore, it expanded the new horizon for the preparation of modular nanoplatform and imaging-guided optical therapy of tumors.

Keywords: Homologous targeting; MR imaging; Metal chelation; Photodynamic therapy; Photothermal therapy.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Image 1
Graphical abstract
Scheme 1
Scheme 1
The synthetic route of biomimetic nanodrugs (DRu/Gd@CM NPs) and its subsequent application in targeted phototherapy of mice subcutaneous breast cancer tumor model.
Fig. 1
Fig. 1
(a, b) TEM images of DRu/Gd NPs with different magnifications; (c) The size distribution of DRu/Gd NPs; (d) EDS elemental maps of C, N, O, Ru and Gd distribution in DRu/Gd NPs; (e) XPS survey spectra of DRu/Gd NPs and the corresponding spectrums of (f) Ru3p and (g) Gd4d; (h) XRD spectra of DRu/Gd NPs; (i) UV–vis absorption of Ru(dcbpy)3Cl2 and DRu/Gd NPs; (j) Fluorescence spectrum of Ru(dcbpy)3Cl2 and DRu/Gd NPs.
Fig. 2
Fig. 2
(a, b) TEM image of DRu/Gd@CM NPs with different magnifications; (c) SDS-PAGE-based protein analyses of DRu/Gd@CM NPs, 4T1 cell membrane and DRu/Gd@CM NPs; (d) Thermal image of the solution with different concentration of DRu/Gd@CM NPs in 10 min; (e) Temperature curve of the solution with different concentration of DRu/Gd@CM NPs in 10 min; (f) Temperature curve of the DRu/Gd@CM NPs solution with different radiated power of in 10 min; (g) Temperature changes of DRu/Gd@CM NPs during five on/off cycles. (h) Longitudinal relaxivity r1 of DRu/Gd@CM NPs and the corresponding T1 and T1map images inserted; (i) The corresponding UV–vis absorption spectra of the mixture of ABDA and the DRu/Gd@CM NPs with different irradiation time periods.
Fig. 3
Fig. 3
(a) Fluorescence images of uptake from L929, MDA-MB-231 and 4T1 cells against DRu/Gd@CM NPs, scale bar: 10 μm; (b)Semi-quantitative analysis indicated targeting for 4T1 cells; (c) CLSM images of intracellular ROS generation from intact 4T1 cells with 660 nm photoirradiation (0.5 W/cm2) in different concentrations (scale bar: 100 μm); (d) Related of fluorescent semi-quantitative analysis of DCFH; (e) The cell viability of 4T1 cells after incubation with a series concentration of DRu/Gd@CM accompanied with different treatments, PDT: irradiated with 660 nm laser, PTT: irradiated with 808 nm laser; (g) Quantification bar plots for live/dead staining; (f) Live/death staining of 4T1 cells after treated with PBS, DRu/Gd@CM, PDT, PTT, and PDT + PTT, Scale bar: 100 μm; (h) Flow cytometry assay of 4T1 cells after being incubated with different group for 24 h.
Fig. 4
Fig. 4
(a) Time-dependent fluorescence imaging of 4T1-Balb/c mice intravenously injected with the DRu/Gd@CM NPs; (b) Quantification of the fluorescence trends of the corresponding treatment; (c) Ex-vivo NIR fluorescence images and (d) related intensity of IR783 in the harvested organs (heart, liver, spleen, lung, kidney) and tumors at 48 h post-administration (n = 3); (e) T1-weighted MR images of mouse Balb/c 4T1 breast cancer in axial and (f) MR signal intensity of tumors before and post the intravenous injection of DRu/Gd@CM NPs.
Fig. 5
Fig. 5
The therapeutic effect of the DRu/Gd@CM NPs on 4T1 tumor model mice. (a) Schematic diagram of the treatment process of tumor-bearing model mice with PDT/PTT; (b) Infrared thermal images and (c) temperature change at the tumor sites of mice bearing 4T1 tumors treated with injection of PBS and DRu/Gd@CM NPs followed by 808-nm laser irradiation (1.5 W/cm2, 10 min). (d, e) tumor volume changes of different groups in 14 days; (f) morphology and (g) tumor weight at the 14 days recorded in different groups; (h) body weight changes of Balb/c mice of different groups; (i) H&E and TUNEL stained images of the tumors from different groups on day 14 (scale bar: 200 μm, n = 3).
Fig. 6
Fig. 6
(a) Ki67 and TNF-α stained images of the tumors from different groups on day 15 (scale bar: 100 μm, n = 3); Quantification of the fluorescence intensity of (b) Ki67 and (c) TNF-α of the corresponding images; (d) H&E histological staining of main organs after intravenous injection of different drug formulations. Scale bar = 100 μm; (e) Blood biochemistry and hematology analysis of mice after different treatments.
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