Magnetic continuum soft robot-driven precise delivery of prodrug nanoassemblies for gastric cancer chemo-immunotherapy

Abstract

Local precise drug delivery is conducive to improving therapeutic efficacy and minimizing off-target toxicity. Current local delivery approaches are focused mostly on superficial or postoperative tumor lesions, due to the challenges posed by the inaccessibility of deep-seated tumors. Herein, we report a magnetic continuum soft robot capable of non-invasive and site-specific delivery of prodrug nanoassemblies-loaded hydrogel. The nanoassemblies are co-assembled from redox-responsive docetaxel prodrug and oxaliplatin prodrug, and subsequently embedded into a hydrogel matrix. The hydrogel precursor and crosslinker are synchronously delivered using the soft robot under magnetic guidance and in situ crosslinked at the gastric cancer lesions, forming a drug depot for sustained release and long-lasting treatment. As the hydrogel gradually degrades, the nanoassemblies are internalized by tumor cells. The redox response ability enables them to be selectively activated within tumor cells to trigger the release of docetaxel and oxaliplatin, exerting a synergistic anti-tumor effect. We find that the combination effectively induces immunogenic cell death of gastric tumor, enhancing antitumor immune responses. This strategy offers an intelligent and controllable integration platform for precise drug delivery and combined chemo-immunotherapy.

Keywords

Magnetic continuum soft robot / Prodrug / Nanoassembly / Hydrogel / Chemo-immunotherapy

Conflicts of interest

The authors declare that there is no conflicts of interest.

Acknowledgments

This work was financially supported by National Natural Science Foundation of China (No. 82161138029), Liaoning Revitalization Talents Program (No. XLYC2402040) and the Project of China-Japan Joint International Laboratory of Advanced Drug Delivery System Research and Translation of Liaoning Province (No. 2024JH2/102100007).

Supplementary materials

Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.ajps.2025.101103. The figures and tables with "S" before the serial number are included in the Supplementary material.

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