Laboratory of Biopharmaceuticals and Nanomedicine, Division of Cancer Research, Regional Cancer Centre, Thiruvananthapuram 695011, India.
Laboratory of Biopharmaceuticals and Nanomedicine, Division of Cancer Research, Regional Cancer Centre, Thiruvananthapuram 695011, India.
Int J Biol Macromol. 2019 Sep 1;136:266-274. doi: 10.1016/j.ijbiomac.2019.06.075. Epub 2019 Jun 12.
Paclitaxel, an effective chemotherapeutic drug, is insoluble in aqueous solvents and is usually administered with excipients which have side effects. The use of this drug is also limited due to multi-drug resistance. In this study polysaccharide nanoparticles are used in the delivery of chemotherapeutic drug while minimizing side-effects, solubility issues and drug resistance. The use of biopolymers like galactoxyloglucan to synthesize nanoparticle makes it more biocompatible. This study involves the synthesis of PST-PTX nanoparticles using tamarind seed polysaccharide and Paclitaxel by epichlorohydrin crosslinking. The particles were further characterized by Dynamic Light Scattering (DLS), High-resolution transmission electron microscopy (HR-TEM) Fourier Transform Infrared Spectroscopy (FTIR) and UV-Visible spectroscopy. The cytotoxicity of PST-PTX nanoparticles in cancer cell lines and resistant cancer cell lines were determined by MTT assay. The quantitative analysis of cell death was determined by Annexin V dead cell assay, Caspase 3/7 assay and expression of pro-apoptotic protein Bax. The ability of the nanoparticle to overcome multi-drug resistance was evaluated by the expression of multidrug-resistant proteins P-glycoprotein (P-gp) and Breast cancer resistant protein (BCRP) in lung adenocarcinoma resistant cells (A549). The present study provides evidence for the ability of PST-PTX nanoparticle to overcome multi-drug resistance and cause apoptotic cell death. The particle was found to be more effective than Paclitaxel in causing cell death in resistant cancer cells. Moreover, the particles were found to downregulate the expression of multi-drug resistant proteins P-gp and BCRP in resistant cell lines suggesting the ability of PST-PTX nanoparticles to overcome multi-drug resistance.
紫杉醇是一种有效的化疗药物，不溶于水溶剂，通常与赋形剂一起使用，而赋形剂具有副作用。由于多药耐药性，该药物的使用也受到限制。在这项研究中，多糖纳米粒子被用于递送电化学治疗药物，同时最大限度地减少副作用、溶解度问题和耐药性。使用半乳甘露聚糖等生物聚合物合成纳米粒子使其更具生物相容性。本研究涉及使用罗望子种子多糖和紫杉醇通过表氯醇交联合成 PST-PTX 纳米粒子。通过动态光散射（DLS）、高分辨率透射电子显微镜（HR-TEM）、傅里叶变换红外光谱（FTIR）和紫外-可见光谱对颗粒进行进一步表征。通过 MTT 测定法测定 PST-PTX 纳米粒子在癌细胞系和耐药癌细胞系中的细胞毒性。通过 Annexin V 死细胞测定、Caspase 3/7 测定和促凋亡蛋白 Bax 的表达来确定细胞死亡的定量分析。通过肺腺癌细胞（A549）中多药耐药蛋白 P-糖蛋白（P-gp）和乳腺癌耐药蛋白（BCRP）的表达来评估纳米粒子克服多药耐药的能力。本研究为 PST-PTX 纳米粒子克服多药耐药并诱导细胞凋亡的能力提供了证据。与紫杉醇相比，该粒子在耐药癌细胞中诱导细胞死亡的效果更好。此外，还发现这些颗粒能够下调耐药细胞系中多药耐药蛋白 P-gp 和 BCRP 的表达，表明 PST-PTX 纳米颗粒具有克服多药耐药的能力。
