Combinatorial Polydopamine-Liposome Nanoformulation as an Effective Anti-Breast Cancer Therapy

Abstract

Wangxing Lu,1,* Wenjie Liu,1,* Anna Hu,1 Jian Shen,1 Hanxi Yi,2 Zeneng Cheng1 1Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410000, People’s Republic of China; 2School of Basic Medical Science, Central South University, Changsha, 410000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hanxi Yi; Wenjie Liu, Email [email protected]; [email protected]: Drug delivery systems (DDSs) based on liposomes are potential tools to minimize the side effects and substantially enhance the therapeutic efficacy of chemotherapy. However, it is challenging to achieve biosafe, accurate, and efficient cancer therapy of liposomes with single function or single mechanism. To solve this problem, we designed a multifunctional and multimechanism nanoplatform based on polydopamine (PDA)-coated liposomes for accurate and efficient combinatorial cancer therapy of chemotherapy and laser-induced PDT/PTT.Methods: ICG and DOX were co-incorporated in polyethylene glycol modified liposomes, which were further coated with PDA by a facile two-step method to construct PDA-liposome nanoparticles (PDA@Lipo/DOX/ICG). The safety of nanocarriers was investigated on normal HEK-293 cells, and the cellular uptake, intracellular ROS production capacity, and combinatorial treatment effect of the nanoparticles were assessed on human breast cancer cells MDA-MB-231. In vivo biodistribution, thermal imaging, biosafety assessment, and combination therapy effects were estimated based on MDA-MB-231 subcutaneous tumor model.Results: Compared with DOX·HCl and Lipo/DOX/ICG, PDA@Lipo/DOX/ICG showed higher toxicity on MDA-MB-231 cells. After endocytosis by target cells, PDA@Lipo/DOX/ICG produced a large amount of ROS for PDT by 808 nm laser irradiation, and the cell inhibition rate of combination therapy reached up to 80.4%. After the tail vein injection (DOX equivalent of 2.5 mg/kg) in mice bearing MDA-MB-231 tumors, PDA@Lipo/DOX/ICG significantly accumulated at the tumor site at 24 h post injection. After 808 nm laser irradiation (1.0 W/cm2, 2 min) at this timepoint, PDA@Lipo/DOX/ICG efficiently suppressed the proliferation of MDA-MB-231 cell and even thoroughly ablated tumors. Negligible cardiotoxicity and no treatment-induced side effects were observed.Conclusion: PDA@Lipo/DOX/ICG is a multifunctional nanoplatform based on PDA-coated liposomes for accurate and efficient combinatorial cancer therapy of chemotherapy and laser-induced PDT/PTT.Keywords: reactive oxygen species, photodynamic therapy, photothermal therapy, polydopamine, liposome

Keywords

• reactive oxygen species
• photodynamic therapy
• photothermal therapy
• polydopamine
• liposome