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Article ORIGINAL RESEARCH  \nDual Sensitization Anti-Resistant Nanoparticles for Treating Refractory Breast Cancers via Apoptosis-Inducing  \nRuijun Ju 1 , 2 , Faliang Wu2 , Yanzhao Tian 1 , Jiahao Chu2 , Xiaoming Peng2 , Xiaobo Wang 1  \n1Pharmacy Department, the 967th Hospital of PLA Joint Logistics Support Force, Dalian, People’s Republic of China; 2Beijing Key Laboratory of Enze Biomass Fine Chemicals, Beijing Institute of Petrochemical Technology, Beijing, People’s Republic of China  \nCorrespondence: Xiaobo Wang, Pharmacy Department, the 967th Hospital of PLA Joint Logistics Support Force, Dalian, People’s Republic of China, Tel/Fax +86-0411-85847131, [Email wxbbenson0653@sina.com](Email wxbbenson0653@sina.com)  \n\n| Purpose: Current chemotherapy fails to offer a desirable efficacy in clinical treatment against breast cancer due to the extensive multi-drug resistance. In this study, we developed dual sensitization anti-resistant nanoparticles to treat refractory breast cancer, aiming to benefit from photodynamic therapy and chemotherapy.\u003Cbr>Methods: Hyaluronic acid (HA) derivative and photosensitizer chlorin e6 (Ce6) derivative were synthesized and confirmed by mass spectrometry. These derivatives and the chemotherapy agent paclitaxel were incorporated into nanoparticles by an emulsion-solvent evaporation method. The prepared nanoparticles were characterized by dynamic laser scattering, atomic force microscopy, and high performance liquid chromatography (HPLC) . The efficacy and mechanisms of the nanoparticles, both in vitro and in vivo, were investigated by flow cytometry, confocal/fluorescence microscopy, and a high-content screening system.\u003Cbr>Results: The prepared dual sensitization anti-resistant nanoparticles were round with a diameter of ~ 100 nm, exhibiting high encapsulation efficiency for the anticancer agent paclitaxel. The nanoparticles demonstrated a robust inhibitory effect against drugresistant breast cancer cells by enhanced uptake, synergistic effect of photodynamic therapy and chemotherapy, and apoptosis-inducing via multiple pathways. In vivo efficacy, biocompatibility and safety were further confirmed acceptable in tumor-bearing mice. Conclusion: The prepared dual sensitization anti-resistant nanoparticles were promising to treat refractory breast cancer with a controllable treatment site and minimal side effects.\u003Cbr>Keywords: dual sensitization anti-resistant nanoparticles, drug-resistant breast cancer, apoptosis, photodynamic therapy, synergistic effect |\n| --- |\n| Introduction\u003Cbr>Breast cancer has become the biggest threat to women’s health, but current therapies cannot provide a desirable efficacy.1 The clinical treatment failure can be mainly attributed to metastasis and multi-drug resistance.2–4 As an essential treatment for malignant tumors, chemotherapy plays an important role in reducing the burden of tumor cells and removing residual tumor cells after surgical treatment. However, free drugs in conventional chemotherapy have no selectivity in vivo, and repeated administration of drugs in large doses will cause acquired drug resistance and severe adverse reactions, eventually leading to treatment failure.\u003Cbr>Generally, multi-drug resistance can be classified into acquired drug resistance and endogenous drug resistance. Acquired drug resistance refers to the drug resistance produced by repeated exposure to chemotherapy drugs, which is mainly characterized by superfluous expression of ATP-binding cassette (ABC) transporters on cell membranes, including p-glycoprotein (P-gP), multi-drug resistance-associated proteins (MRPs), and the breast cancer drug resistance protein (BCRP) .5 The overexpression of these transporters leads to increased drug efflux and decreased uptake, thereby reducing the efficacy of chemotherapy. However, endogenous drug resistance exists in tumor cells or stem","cbCaijl5pLTQETAg","https://ap.wps.com/l/cbCaijl5pLTQETAg","pdf",9440287,16,"English","# Purpose\n# Methods\n# Results\n# Conclusion\n# Introduction\n# Photodynamic Therapy Background\n# Chlorin e6 (Ce6) and Laser Activation","[{\"question\":\"What problem does the study target in breast cancer treatment?\",\"answer\":\"The study targets treatment failure caused by extensive multi-drug resistance, which reduces the efficacy of current chemotherapy against breast cancer.\"},{\"question\":\"How are the dual sensitization nanoparticles prepared?\",\"answer\":\"Hyaluronic acid derivative and chlorin e6 derivative are synthesized, combined with paclitaxel, and incorporated into nanoparticles using an emulsion-solvent evaporation method.\"},{\"question\":\"What mechanisms contribute to the nanoparticles’ antitumor effect?\",\"answer\":\"They enhance uptake, produce a synergistic effect between photodynamic therapy and chemotherapy, and induce apoptosis through multiple pathways.\"}]","Dual Sensitization Anti-Resistant Nanoparticles for Treating Refractory Breast Cancers via Apoptosis-Inducing | PDF",1790263356]