A multi-functionalized nanocomposite constructed by gold nanorod core with triple-layer coating to combat multidrug resistant colorectal cancer

Y Jiang, Z Guo, J Fang, B Wang, Z Lin, ZS Chen… - Materials Science and …, 2020 - Elsevier
Y Jiang, Z Guo, J Fang, B Wang, Z Lin, ZS Chen, Y Chen, N Zhang, X Yang, W Gao
Materials Science and Engineering: C, 2020Elsevier
Multi-drug resistance (MDR) remains the main culprit for the low survival rate of advanced
colorectal cancer (CRC). Photothermal-therapy (PPT) is effective to kill MDR tumor cells, but
fails to completely eradicate tumors. In this study, we prepared a nanocomposite based on
gold nanorod core with triple layer coating (GNRs/mSiO 2/PHIS/TPGS/DOX) to combat
multidrug resistant (MDR) colorectal cancer via multi-strategies. We first synthesized the
mesoporous silica-coated gold nanorods (GNRs/mSiO 2), and loaded with antitumor drug …
Abstract
Multi-drug resistance (MDR) remains the main culprit for the low survival rate of advanced colorectal cancer (CRC). Photothermal-therapy (PPT) is effective to kill MDR tumor cells, but fails to completely eradicate tumors. In this study, we prepared a nanocomposite based on gold nanorod core with triple layer coating (GNRs/mSiO2/PHIS/TPGS/DOX) to combat multidrug resistant (MDR) colorectal cancer via multi-strategies. We first synthesized the mesoporous silica-coated gold nanorods (GNRs/mSiO2), and loaded with antitumor drug doxorubicin (DOX) to realize a combination of chemo- and photothermal-therapy. To reverse DOX resistance, pH responsive poly-histidine (PHIS) was conjugated on GNRs/mSiO2 to increase drug intracellular accumulation via efficient endo/lysosome escape; d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) was then assembled on the surface of the particles to realize drug intracellular retention by inhibition P-glycoprotein. The results showed that the nanocomposite exhibited a highly efficient photothermal conversion in the NIR region, a pH and NIR triggered drug release profile and an increment of DOX intracellular accumulation and cytotoxicity on MDR SW620/Ad300 cells. Most importantly, the nanocomposite showed the most potent antitumor efficacy without obvious systemic toxicity comparing to other control groups with either chemo- or photothermal therapy alone on SW620/Ad300 tumor bearing mice. Altogether, the successful preparation of the nanocomposite and its potent efficacy might provide evidence for the future design and develop of nano-therapeutic system in the treatment of MDR colorectal cancer.
Elsevier
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