Nanotheranostics 2019; 3(3):266-283. doi:10.7150/ntno.36842
Polydopamine-coated gold nanostar for combined antitumor and antiangiogenic therapy in multidrug-resistant breast cancer
1. Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan, ROC
2. Department of Chemistry, National Taiwan University, Taipei 10617, Taiwan, ROC
You YH, Lin YF, Nirosha B, Chang HT, Huang YF. Polydopamine-coated gold nanostar for combined antitumor and antiangiogenic therapy in multidrug-resistant breast cancer. Nanotheranostics 2019; 3(3):266-283. doi:10.7150/ntno.36842. Available from http://www.ntno.org/v03p0266.htm
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.
Keywords: Gold nanostar, Polydopamine, Antiangiogenesis, Cancer combination therapy, Drug delivery, Multidrug resistance