Nanodrug Formed by Coassembly of Dual Anticancer Drugs to Inhibit Cancer Cell Drug Resistance.
Carrier-free pure nanodrugs (PNDs) that are composed entirely of pharmaceutically active molecules are regarded as promising candidates to be the next generation of drug formulations and are mainly formulated from supramolecular self-assembly of drug molecules. It benefits from the efficient use of drug compounds with poor aqueous solubility and takes advantage of nanoscale drug delivery systems. Here, a type of all-in-one nanoparticle consisting of multiple drugs with enhanced synergistic antiproliferation efficiency against drug-resistant cancer cells has been created. To nanoparticulate the anticancer drugs, 10-hydroxycamptothecin (HCPT) and doxorubicin (DOX) were chosen as a typical model. The resulting HD nanoparticles (HD NPs) were formulated by a "green" and convenient self-assembling method, and the water-solubility of 10-hydroxycamptothecin (HCPT) was improved 50-fold after nanosizing by coassembly with DOX. The formation process was studied by observing the morphological changes at various reaction times and molar ratios of DOX to HCPT. Molecular dynamics (MD) simulations showed that DOX molecules tend to assemble around HCPT molecules through intermolecular forces. With the advantage of nanosizing, HD NPs could improve the intracellular drug retention of DOX to as much as 2-fold in drug-resistant cancer cells (MCF-7R). As a dual-drug-loaded nanoformulation, HD NPs effectively enhanced drug cytotoxicity to drug-resistant cancer cells. The combination of HCPT and DOX exhibited a synergistic effect as the nanosized HD NPs improved drug retention in drug-resistant cancer cells against P-gp efflux in MCF-7R cells. Furthermore, colony forming assays were applied to evaluate long-term inhibition of cancer cell proliferation, and these assays confirmed the greatly improved cytotoxicity of HD NPs in drug-resistant cells compared to free drugs.
Chinese Academy of Sciences (CAS) , Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, No. 11, First North Road, Zhongguancun, Beijing 100190, China.
Yuanyuan
Y
Zhao
Chinese Academy of Sciences (CAS) , Key Laboratory for Biological 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.
Fei
F
Chen
Chinese Academy of Sciences (CAS) , Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, No. 11, First North Road, Zhongguancun, Beijing 100190, China.
Yuanming
Y
Pan
Chinese Academy of Sciences (CAS) , Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, No. 11, First North Road, Zhongguancun, Beijing 100190, China.
Zhipeng
Z
Li
Chinese Academy of Sciences (CAS) , Key Laboratory for Biological 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.
Xiangdong
X
Xue
Chinese Academy of Sciences (CAS) , Key Laboratory for Biological 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.
Chukwunweike Ikechukwu
CI
Okeke
Chinese Academy of Sciences (CAS) , Key Laboratory for Biological 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.
Yifeng
Y
Wang
Chinese Academy of Sciences (CAS) , Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, No. 11, First North Road, Zhongguancun, Beijing 100190, China.
Chan
C
Li
Département de Chimie, Centre Interdisciplinaire de Nanoscience de Marseille, CNRS UMR 7325, Aix-Marseille Université , 163 Avenue de Luminy 13288, Marseille, France.
Ling
L
Peng
Molecular Imaging Laboratory, Department of Radiology, Howard University , Washington D.C. 20060, United States.
Paul C
PC
Wang
Chinese Academy of Sciences (CAS) , Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, No. 11, First North Road, Zhongguancun, Beijing 100190, China.
Xiaowei
X
Ma
Chinese Academy of Sciences (CAS) , Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, No. 11, First North Road, Zhongguancun, Beijing 100190, China.
Xing-Jie
XJ
Liang
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D003114:Colony-Forming Units Assay; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D005434:Flow Cytometry; D006801:Humans; D056004:Molecular Dynamics Simulation; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D054118:Nanospheres / Q000737:chemistry / Q000648:ultrastructure; D043942:Nanotubes / Q000737:chemistry / Q000648:ultrastructure; D013050:Spectrometry, Fluorescence
D000970:Antineoplastic Agents; D004317:Doxorubicin; C028098:10-hydroxycamptothecin; D002166:Camptothecin
assemble; carrier-free; drug resistance; insoluble drugs; pure nanodrug