Indulekha S, Arunkumar P, Bahadur D, Srivastava R
Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India.
Centre for Research in Nanotechnology and Science, Indian Institute of Technology Bombay, Mumbai 400076, India.
Colloids Surf B Biointerfaces. 2017 Jul 1;155:304-313. doi: 10.1016/j.colsurfb.2017.04.035. Epub 2017 Apr 19.
With the onset of hyperthermia and their advantage in increasing vascular perfusion and permeability in the cancer milieu, thermo-responsive polymers have become an attractive candidate for designing therapeutic nano-vehicles for targeted on-demand delivery of bioactive agents. For this purpose, we developed a dual (thermo- and pH-) responsive nanotherapeutic composite system rendering a combinational therapy of hyperthermia mediated drug delivery. This composite system comprises of magnetic chitosan-g-PNVCL (MCP) polymeric nanogels loaded with anticancer drug, Doxorubicin (DOX). The size distribution and the stability of the MCP nanogels have been characterized using DLS and Zeta-potential studies. XRD and TG-DTA confirms the presence of magnetic nanoparticles loaded onto MCP nanogel. ICP-AES analysis was done to determine the amount of iron content in the MCP nanogels. The magnetic property of the MCP nanogels was estimated to be ∼37 emu/g using Vibrating Sample Magnetometer (VSM). The heating ability of MCP nanogels was calculated to be ∼204W/g for the concentration of 2mg/mL using time-dependent Specific Absorption Rate (SAR) method. Magnetic field induced thermo-responsive and pH responsive drug release studies were carried out and it was found that MCP nanogels have a good on-demand drug release properties. The DOX-MCP nanogels were evaluated for its in vitro killing efficacy of breast cancer cells MCF 7 and MDAMB 231 cells with synergistic effects of both hyperthermia and chemotherapy in presence of magnetic field at the concentration of 2mg/mL. Thus, MCP nanogels can be a potential dual modal on-demand hyperthermia mediated drug delivery platform for the breast cancer treatment.
随着热疗的出现以及它们在增加癌症环境中血管灌注和通透性方面的优势，热响应聚合物已成为设计用于生物活性剂靶向按需递送的治疗性纳米载体的有吸引力的候选者。为此，我们开发了一种双（热和pH）响应纳米治疗复合系统，实现热疗介导的药物递送的联合治疗。该复合系统由负载抗癌药物阿霉素（DOX）的磁性壳聚糖-g-PNVCL（MCP）聚合物纳米凝胶组成。使用动态光散射（DLS）和zeta电位研究对MCP纳米凝胶的尺寸分布和稳定性进行了表征。X射线衍射（XRD）和热重-差示热分析（TG-DTA）证实了负载在MCP纳米凝胶上的磁性纳米颗粒的存在。进行电感耦合等离子体原子发射光谱（ICP-AES）分析以确定MCP纳米凝胶中铁的含量。使用振动样品磁强计（VSM）估计MCP纳米凝胶的磁性约为37 emu/g。使用时间依赖性比吸收率（SAR）方法计算出2mg/mL浓度下MCP纳米凝胶的加热能力约为204W/g。进行了磁场诱导的热响应和pH响应药物释放研究，发现MCP纳米凝胶具有良好的按需药物释放特性。在2mg/mL浓度的磁场存在下，评估了DOX-MCP纳米凝胶对乳腺癌细胞MCF 7和MDAMB 231细胞的体外杀伤效果，以及热疗和化疗的协同作用。因此，MCP纳米凝胶可以成为用于乳腺癌治疗的潜在双模态按需热疗介导的药物递送平台。
