摘要
Combination therapy via nanoparticulate systems has already been proposed as a synergistic approach for cancer treatment. Herein, undecylenic acid modified thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs) loaded with sorafenib and surface-biofunctionalized with anti-CD326 antibody (Ab) were developed for cancer chemo-immunotherapy in MCF-7 and MDA-MB-231 breast cancer cells. The cytocompatibility study showed no significant toxicity for the bare and antibody-conjugated UnTHCPSi (Un-Ab) NPs at concentrations lower than 200 μg·mL^-1. Compared to the bare UnTHCPSi, Un-Ab NPs loaded with sorafenib reduced the premature drug release in plasma, increasing the probability of proper drug targeting. In addition, high cellular interaction and subsequent internalization of the Un-Ab NPs into the cells expressing CD326 antigen demonstrated the possibility of improving antigen-mediated endocytosis via CD326 targeting. While an in vitro antitumor study revealed a higher inhibitory effect of the sorafenib-loaded Un-Ab NPs compared to the drug-loaded UnTHCPSi NPs in the CD326 positive MCF-7 cells, there was no difference in the anti-proliferation impact of both the abovementioned NPs in the CD326 negative MDA-MB-231 cells, suggesting CD326 as an appropriate receptor for Ab-mediated drug delivery. It was also shown that the anti-CD326 Ab can act as an immunotherapeutic agent by inducing antibody dependent cellular cytotoxicity and enhancing the interaction of effector immune and cancer cells for subsequent phagocytosis and cytokine secretion. Hence, the developed nanovectors can be applied for simultaneous tumor-selective drug targeting and immunotherapy.
经由 nanoparticulate 系统的联合治疗已经为癌症治疗作为一条 synergistic 途径被建议了。此处, undecylenic 酸热地修改了多孔的硅 nanoparticles (UnTHCPSi NP ) 与 sorafenib 装载了的 hydrocarbonized,有 anti-CD326 抗体(Ab ) 的 surface-biofunctionalized 在 MCF-7 和 MDA-MB-231 乳癌房间为癌症 chemo 免疫疗法被开发。cytocompatibility 学习没在比 200 g 低的集中为赤裸、结合抗体的 UnTHCPSi (Un-Ab ) NP 显示出重要毒性 ? 浩汰楹杮愠搠 ' 糖锚?湩琠敨漠潸桰汩捩瑩 ? 景琠敨猠牵慦散倠 ? 瑡浯吗?