| Summary: | Cheng Wang,1,* Min Han,1,2,* Xuerong Liu,1 Shaoqing Chen,1 Fuqiang Hu,1 Jihong Sun,3 Hong Yuan1 1Department of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; 2Hangzhou Zhongmei Huadong Pharmaceutical Co, Ltd, Hangzhou 310011, China; 3Department of Radiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China *These authors contributed equally to this work Background: The application of mitoxantrone (MIT) in cancer therapy has been severely limited by its inherent drawbacks. In addition, effective cancer therapy calls for drug release systems capable of enforcing drug release within cancer cells in response to infinite stimulant with enhanced drug penetration capability. Methods: MIT-preloaded phospholipid-amorphous calcium carbonate hybrid nanoparticles (PL/ACC-MIT) that surface modified with PL shell (containing shielding polymer polyethylene glycol and targeting moiety folic acid) were prepared by a facile solvent-diffusion method. Results: It has been proven that the resulting PL/ACC-MIT nanoparticles demonstrated satisfactory stability against various aqueous environments with minimal drug leakage and exerted strong targeting capability but selective preference to the folate receptor-overexpressing cell line. In contrast, once exposed to the enzyme-abundant and acidic environments of cancer cells, the PL/ACC-MIT nanoparticles can readily decompose to facilitate quick drug release and enhanced drug penetration to yield preferable antitumor effect both in vitro and in vivo. Conclusion: In this study, MIT-preloaded water-responsive hybrid nanoparticles with increased stability, targetability, controlled drug release, and enhanced drug penetration were successfully developed, which might be a candidate for targeted and effective cancer therapy. Keywords: mitoxantrone, water responsive, hybrid nanoparticles, amorphous calcium carbonate, cancer therapy
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