Enzyme Degradable Hyperbranched Polyphosphoester Micellar Nanomedicines for NIR Imaging-Guided Chemo-Photothermal Therapy of Drug-Resistant Cancers.

Abstract

Multidrug resistance (MDR) is the major cause for chemotherapy failure, which constitutes a formidable challenge in the field of cancer therapy. The synergistic chemo-photothermal treatment has been reported to be a potential strategy to overcome MDR. In this work, rationally designed enzyme-degradable, hyperbranched polyphosphoester nanomedicines were developed for reversing MDR via the codelivery of doxorubicin and IR-780 (hPPEDOX&IR) as combined chemo-photothermal therapy. The amphiphilic hyperbranched polyphosphoesters with phosphate bond as the branching point were synthesized via a simple but robust one-step polycondensation reaction. The self-assembled hPPEDOX&IR exhibited good serum stability, sustained release, preferable tumor accumulation, and enhanced drug influx of doxorubicin in resistant MCF-7/ADR cells. Moreover, the degradation of hPPEDOX&IR was accelerated in the presence of alkaline phosphatase, which was overexpressed in various cancers, resulting in the fast release of encapsulated doxorubicin. The enzyme-degradable polymer generated synergistic chemo-photothermal cytotoxicity against MCF-7/ADR cells and, thus, the efficient ablation of DOX-resistant tumor without regrowth. This delivery system may open a new avenue for codelivery of chemo- and photothermal therapeutics for MDR tumor therapy.

• Authors: Mengqun Yao, Yinchu Ma, Hang Liu, Malik Ihsanullah Khan, Song Shen, Shuya Li, Yangyang Zhao, Yi Liu, Guoqing Zhang, Xiaoqiu Li, Fei Zhong, Wei Jiang, Yucai Wang
• Journal: Biomacromolecules (Biomacromolecules) Vol. 19 Issue 4 Pg. 1130-1141 (04 09 2018) ISSN: 1526-4602 [Electronic] United States
• PMID: 29514006 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2-(2-(2-chloro-3-((1,3-dihydro-3,3-dimethyl-1-propyl-2H-indol-2-ylidene)ethylidene)-1-cyclohexen-1-yl)ethenyl)-3,3-dimethyl-1-propylindolium
• Indoles
• Doxorubicin

Topics

• Combined Modality Therapy
• Doxorubicin (chemistry, pharmacology)
• Drug Delivery Systems
• Drug Resistance, Multiple (drug effects)
• Drug Resistance, Neoplasm (drug effects)
• Drug Therapy (methods)
• Humans
• Indoles (chemistry, pharmacology)
• MCF-7 Cells
• Nanomedicine
• Neoplasms (drug therapy)
• Phototherapy