ABSTRACT
In the development of chemo-immunotherapy, many efforts have been focusing on designing suitable carriers to realize the co-delivery of chemotherapeutic and immunotherapeutic with different physicochemical properties and mechanisms of action. Besides, rapid drug release at the tumor site with minimal drug degradation is also essential to facilitate the antitumor effect in a short time. Here, we reported a cancer cell membrane-coated pH-responsive nanogel (NG@M) to co-deliver chemotherapeutic paclitaxel (PTX) and immunotherapeutic agent interleukin-2 (IL-2) under mild conditions for combinational treatment of triple-negative breast cancer. In the designed nanogels, the synthetic copolymer PDEA-co-HP-β-cyclodextrin-co-Pluronic F127 and charge reversible polymer dimethylmaleic anhydride-modified polyethyleneimine endowed nanogels with excellent drug-loading capacity and rapid responsive drug-releasing behavior under acidic tumor microenvironment. Benefited from tumor homologous targeting capacity, NG@M exhibited 4.59-fold higher accumulation at the homologous tumor site than heterologous cancer cell membrane-coated NG. Rapidly released PTX and IL-2 enhanced the maturation of dendritic cells and quickly activated the antitumor immune response in situ, followed by prompted infiltration of immune effector cells. By the combined chemo-immunotherapy, enhanced antitumor effect and efficient pulmonary metastasis inhibition were achieved with a prolonged median survival rate (39 days).
ABSTRACT
OBJECTIVE: To investigate a biomimetic nano-targeted drug modifide by cancer cell membrane and to discuss its efficiency in breast cancer. METHODS: The lac-DOX/DOX was prepared by filming-rehydration method, and the 4T1 cell membrane was extracted at the same time. The lac-DOX /DOX@4T1m was prepared by sonication method.. The morphology of lac-DOX /DOX@4T1m was observed by a transmission electron microscopy. The protein on 4T1 cell membrane was analyzed by gel electrophoresis. The targeting of drugs to homologous cancer cells in vivo and in vitro were evaluated by cell uptake experiments and imaging experiments of small animals. 4T1 tumor-bearing Balb/c mice were built, the anti-tumor efficacy and biosafety of lac-DOX/ DOX@4t1m were evaluated. RESULTS: The prepared lac-DOX /DOX@4T1m have a regular spherical shape with an average particle diameter of (204.8±13.0)nm, and the protein entirety remained on the cell membrane. The results of cell uptake experiments and in vivo imaging experiments of mice showed that lac-DOX/DOX@4T1m can target 4T1 cells. Antitumor test results showed that lac-DOX/ DOX@4T1m could inhibit tumor growth more effectively and significantly reduce the damage to liver function. CONCLUSION: In this study, a bionic nano-drug is successfully prepared, which improve the tumor targeting and therapeutic effect, reduce the toxic effects of adriamycin, and improve the drug safety.