title: Synergistically Enhanced Therapeutic Effect of a Carrier-Free HCPT/DOX Nanodrug on Breast Cancer Cells through Improved Cellular Drug Accumulation.
abstract: We are interested in developing systems for simultaneous delivery of two or more chemotherapeutic agents. Simple physical mixing of drugs may reduce the therapeutic effect and cause unexpected or even dangerous side-effects. For example, when 10-hydroxycamptothecin (HCPT) and doxorubicin (DOX) injection solutions are mixed, the curative effect is actually reduced in clinical practice. In this study we demonstrated that when HCPT and DOX are combined into a single nanoparticle, their toxicity to tumor cells in vitro is synergistically enhanced. We used a simple and "green" reprecipitation method to successfully create a carrier-free dual-drug delivery system by self-nanocrystallization of the drug molecules. When HCPT and DOX were coassembled, they formed small, spherical nanodrug particles with a positive surface charge. Cellular uptake of HCPT was improved and nuclear accumulation increased as much as 1.57-fold in comparison to HCPT alone. The carrier-free HCPT/DOX nanoparticles demonstrated enhanced synergistic cytotoxicity against breast cancer cells in vitro, while an antagonistic effect was observed when HCPT and DOX were directly mixed at high concentration.
authors.affiliation: †Laboratory of Controllable Nanopharmaceuticals, Chinese Academy of Sciences (CAS), Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, No. 11, First North Road, Zhongguancun, Beijing 100190, China.|‡University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.affiliation: †Laboratory of Controllable Nanopharmaceuticals, Chinese Academy of Sciences (CAS), Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, No. 11, First North Road, Zhongguancun, Beijing 100190, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: †Laboratory of Controllable Nanopharmaceuticals, Chinese Academy of Sciences (CAS), Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, No. 11, First North Road, Zhongguancun, Beijing 100190, China.
authors.forename: Yuanming
authors.initials: Y
authors.lastname: Pan
authors.affiliation: †Laboratory of Controllable Nanopharmaceuticals, Chinese Academy of Sciences (CAS), Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, No. 11, First North Road, Zhongguancun, Beijing 100190, China.|‡University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Xue
authors.affiliation: †Laboratory of Controllable Nanopharmaceuticals, Chinese Academy of Sciences (CAS), Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, No. 11, First North Road, Zhongguancun, Beijing 100190, China.|‡University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: †Laboratory of Controllable Nanopharmaceuticals, Chinese Academy of Sciences (CAS), Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, No. 11, First North Road, Zhongguancun, Beijing 100190, China.|‡University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
authors.affiliation: †Laboratory of Controllable Nanopharmaceuticals, Chinese Academy of Sciences (CAS), Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, No. 11, First North Road, Zhongguancun, Beijing 100190, China.
authors.forename: Xing-Jie
authors.initials: XJ
authors.lastname: Liang
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology*; D004337:Drug Carriers / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000379:methods; D004357:Drug Synergism; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000008:administration & dosage*
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; C527042:hydroxycamptothecinum; D004317:Doxorubicin; D002166:Camptothecin
keywords: 10-hydroxycamptothecin; doxorubicin; dual-drug nanoparticle; pure drug nanoparticle; synergistic therapy