金纳米棒核三层包被多功能纳米复合物抗击多药耐药结直肠癌的研究

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/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 doxorubicin (DOX) to realize a combination of chemo- and photothermal-therapy. To reverse DOX resistance, pH responsive poly-histidine (PHIS) was conjugated on GNRs/mSiO 2 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.