Folic acid modified cell membrane capsules encapsulating doxorubicin and indocyanine green for highly effective combinational therapy in vivo.

A combination of chemotherapy and phototherapy has emerged as a promising strategy for cancer treatment. To achieve effective combinational therapy of cancer with reduced toxicity, it is highly desirable to improve the targeting of chemotherapeutic and near-infrared photosensitizers to enhance their accumulation in tumor. Here we report a novel tumor targeting cell membrane capsule (CMC), originate from living cells, to load doxorubicin hydrochloride (DOX) and indocyanine green (ICG), for combinational photo-chemotherapy against cancer. As a result, folic acid modified CMC (CMC-FA, with a diameter about 200 nm and a FA density of 0.4 molecule/nm2 ) showed 3-4 fold higher cell uptake by cancer cells in vitro and 2.3 times higher accumulation in mouse cancer xenografts in vivo than pristine CMC. DOX and ICG with therapeutically significant concentrations can be sequentially encapsulated into CMC-FA by temporary permeating the plasma membranes with high efficiency. The systematic administration of cancer targeting CMC-FA loaded with DOX and ICG could significantly inhibit tumor growth in mouse xenografts in the presence of a near-infrared light at 808 nm, without noticeable toxicity. These findings suggest that cancer targeting CMC may have considerable benefits in drug delivery and combinational cancer therapy.

STATEMENT OF SIGNIFICANCE: A combination of chemotherapy and photothermal/photodynamic therapy has emerged as a promising strategy for cancer therapy. In current study, a novel cancer targeting cell membrane capsule (CMC-FA), originate from living cells and surface modified with folic acid, was developed to load doxorubicin hydrochloride (DOX) and indocyanine green (ICG), for combinational photo-chemotherapy against cancer. The systematic administration of drug loaded CMC-FA can significantly inhibit tumor growth in mouse xenografts in the presence of a near-infrared light at 808 nm, without noticeable toxicity. This study provides a simple and robust strategy to develop biocompatible therapeutic cell membrane capsules, holds strong translational potential in precise cancer treatment.