Preparation and evaluation of paclitaxel-loaded reactive oxygen species and glutathione redox-responsive poly(lactic-co-glycolic acid) nanoparticles for controlled release in tumor cells.

Aim: To formulate and assess the anticancer effect of the poly(lactic-co-glycolic acid) (PLGA) copolymer with the thioether groups (diethyl sulfide [Des]) and disulfide bond (cystamine containing disulfide [Cys]), which encapsulated the anticancer drug paclitaxel (PTX) and triggered PTX release in cancer cell H₂O₂-rich or glutathione-rich surroundings. Methods: PLGA-b-P (Des@Cys) and PLGA-b-P nanoparticles loaded with PTX were prepared and characterized in vitro. The delivery ability of the PLGA-b-P nanoparticles and PLGA-b-P-PTX nanoparticles was assessed on a CT26 (mouse colon cancer cell line) and mouse lung cancer LLC model. Results: The nanoparticles were successfully prepared. Compared with free PTX, the formulated PLGA-b-P nanoparticles loaded with PTX exhibited greater accumulation at the tumor site in the mouse model. Conclusion: PLGA-b-P nanoparticles promote drug accumulation at tumor sites, providing an effective strategy for an intelligent, responsive drug-delivery system. Cancer is one of the diseases with the highest mortality rate in the world. Chemotherapy is the most frequently used method of cancer treatment. However, traditional chemotherapeutic drugs have the disadvantages of lack of specificity, high toxicity to the human body, lack of tumor targeting, inability to exist stably in the body, ease of clearance by the body and drug resistance to tumors, so clinical application is limited. Paclitaxel is widely used in the treatment of various cancers, and its use is limited due to the above disadvantages. The purpose of this study was to construct a nanodelivery system with dual responses to the tumor microenvironment, enabling the efficient accumulation of paclitaxel in solid tumors through the enhanced permeability and retention effect, enhancing the therapeutic effect of cancer. This study also investigated the intravenous safety of this dual-responsive nanodelivery system. It evaluated the toxic effects of drug-loaded nanoparticles on cancer cells and validated the controlled release of nanoparticles at tumor sites by in vivo imaging in mice. The authors concluded that tumor microenvironment dual-responsive nanoparticles are a novel and promising nanodelivery system as an intelligently responsive anticancer agent with great promise in future clinical trials. This study prepared polymer nanocarriers (PLGA-b-p-NPs) with double response to the tumor microenvironment and loaded with traditional antitumor drug paclitaxel, so that drugs can accurately reach tumor cells and be rapidly released in cells. [ABSTRACT FROM AUTHOR]