期刊
ADVANCED HEALTHCARE MATERIALS
卷 9, 期 5, 页码 -出版社
WILEY
DOI: 10.1002/adhm.201901582
关键词
controlled release; gas therapy; long circulation; multidrug resistance; sulfur dioxide
资金
- National Natural Science Foundation of China [51872188, 51873041, 51473037, 51933002]
- National Key RAMP
- D Program of China [2016YFC1100300, 2018YFC1602301]
- Special Funds for the Development of Strategic Emerging Industries in Shenzhen [20180309154519685]
- Shenzhen Basic Research Program [JCYJ20170302151858466, JCYJ20170818093808351]
- Shenzhen Peacock Plan [KQTD2016053112051497]
Multiple drug resistance (MDR) exhibited by cancer cells and low intratumor accumulation of chemotherapeutics are the main obstacles in cancer chemotherapy. Herein, the preparation of a redox-responsive sulfur dioxide (SO2)-releasing nanosystem, with high SO2-loading capacity, aimed at improving the treatment efficacy of cancers exhibiting MDR is described. The multifunctional nanomedicine (MON-DN@PCBMA-DOX) is designed and constructed by coating mesoporous organosilica nanoparticles with a zwitterionic polymer, poly(carboxybetaine methacrylate) (PCBMA), which can concurrently load SO2 prodrug molecules (DN, 2,4-dinitrobenzenesulfonylchloride) and chemotherapeutics (DOX, doxorubicin). The generated SO2 molecules can sensitize cells to chemotherapy and overcome the MDR by downregulating the expression of P-glycoprotein. Furthermore, the PCBMA coating prolongs the blood circulation time of the inner core, leading to an increased intratumor accumulation of the nanomedicine. Owing to the prolonged blood circulation, enhanced tumor accumulation, and SO2 sensitization of cells to chemotherapy, the nanomedicine exhibits excellent tumor suppression with a tumor inhibition rate of 94.8%, and might provide a new platform for cancer therapy.
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