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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.
AuthorsFei Chen, Yuanyuan Zhao, Yuanming Pan, Xiangdong Xue, Xu Zhang, Anil Kumar, Xing-Jie Liang
JournalMolecular pharmaceutics (Mol Pharm) Vol. 12 Issue 7 Pg. 2237-44 (Jul 06 2015) ISSN: 1543-8392 [Electronic] United States
PMID25996761 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibiotics, Antineoplastic
  • Drug Carriers
  • hydroxycamptothecinum
  • Doxorubicin
  • Camptothecin
Topics
  • Antibiotics, Antineoplastic (pharmacology)
  • Breast Neoplasms (drug therapy)
  • Camptothecin (analogs & derivatives, pharmacology)
  • Cell Line, Tumor
  • Doxorubicin (pharmacology)
  • Drug Carriers (pharmacology)
  • Drug Delivery Systems (methods)
  • Drug Synergism
  • Female
  • Humans
  • MCF-7 Cells
  • Nanoparticles (administration & dosage)

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