HSA-nanobinders crafted from bioresponsive prodrugs for combined cancer chemoimmunotherapy-an in vitro exploration

由生物反应性前药制成的 HSA 纳米粘合剂用于联合癌症化学免疫治疗——一项体外探索

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作者:Matilde Tubertini #, Luca Menilli #, Celeste Milani #, Cecilia Martini, Maria Luisa Navacchia, Marta Nugnes, Manuela Bartolini, Marina Naldi, Daniele Tedesco, Elisa Martella, Andrea Guerrini, Claudia Ferroni, Francesca Moret, Greta Varchi

Discussion

Our data show that NB@5 effectively binds to HSA in cell-free experiments, demonstrating its protective role in the controlled release of drugs and suggesting the potential to exploit the protein as the endogenous vehicle for targeted delivery to the tumor site. Our study successfully proves that the drugs encapsulated within the NBs are preferentially released under the altered redox conditions commonly found in the tumor microenvironment, thereby inducing cell death, promoting ICD, and inhibiting IDO1.

Methods

This work describes the development of novel biomimetic and carrier-free nanobinders (NBs) loaded with both paclitaxel and the IDO1 inhibitor NLG919 in the form of bioresponsive and biomimetic prodrugs. A fine tuning of the preparation conditions allowed to identify NB@5 as the most suitable nanoformulation in terms of reproducibility, stability and in vitro effectiveness.

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