Polydopamine-coated gold nanostar for combined antitumor and antiangiogenic therapy in multidrug-resistant breast cancer
Journal
Nanotheranostics
Journal Volume
3
Journal Issue
3
Pages
266-283
Date Issued
2019
Author(s)
Abstract
Cancer combination therapy can improve treatment efficacy and is widely utilized in the biomedical field. In this paper, we propose a facile strategy to develop a polydopamine (PDA)-coated Au nanostar (NS@PPFA) as a multifunctional nanoplatform for cancer targeting and combination therapy. The Au nanostar demonstrated high photothermal conversion efficiency because of the tip-enhanced plasmonic effect. Modification of PDA and folic acid on the NS surface improved its drug-loading efficiency and targeting capability. In vitro, compared with nontargeted cells, targeted breast cancer MCF-7 cells demonstrated efficient uptake of chemodrug-loaded NS-D@PPFA through the receptor-mediated endocytosis pathway. In combination with the photothermal effect induced by near-infrared laser irradiation, controlled payload release could be activated in response to both internal (acid) and external (photothermal) stimuli, leading to an efficient chemo-photothermal action against MCF-7 cells and drug-resistant MCF-7/ADR cells. By contrast, cellular damage was less obvious in normal HaCaT (human skin keratinocytes) and NIH-3T3 cells (murine fibroblasts). In addition, payload-free NS@PPFA exhibited a high binding affinity (Kd = 2.68 × 10-10 M) toward vascular endothelial growth factor (VEGF-A165), which was at least two orders of magnitude stronger than that of highly abundant plasma proteins, such as human serum albumin. Furthermore, in vitro study showed that NS@PPFA could effectively inhibit VEGF-A165-induced proliferation, migration, and tube formation of human umbilical vein endothelial cells, resulting in additional therapeutic benefits for eradicating tumors through a simultaneous antiangiogenic action in chemo-photothermal treatment. The combined treatment also exhibited the lowest microvessel density, leading to a potent antitumor effect in vivo. Overall, our "all-in-one" nanoplatform is highly promising for tumor therapy, enabling effective treatment against multidrug-resistant cancers.
Subjects
Antiangiogenesis; Cancer combination therapy; Drug delivery; Gold nanostar; Multidrug resistance; Polydopamine
SDGs
Other Subjects
angiogenesis inhibitor; antineoplastic agent; gold; indole derivative; nanoparticle; polydopamine; polymer; vasculotropin A; angiogenesis; animal; apoptosis; breast tumor; cell motion; cell proliferation; chemistry; drug effect; drug release; drug resistance; endocytosis; female; human; MCF-7 cell line; metabolism; mouse; multidrug resistance; NIH 3T3 cell line; nude mouse; phototherapy; temperature; thermotherapy; time factor; tissue distribution; ultrastructure; umbilical vein endothelial cell; Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Apoptosis; Breast Neoplasms; Cell Movement; Cell Proliferation; Drug Liberation; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Endocytosis; Female; Gold; Human Umbilical Vein Endothelial Cells; Humans; Hyperthermia, Induced; Indoles; MCF-7 Cells; Mice; Mice, Nude; Nanoparticles; Neovascularization, Physiologic; NIH 3T3 Cells; Phototherapy; Polymers; Temperature; Time Factors; Tissue Distribution; Vascular Endothelial Growth Factor A
Type
journal article