Shanavas Asifkhan, Sasidharan Sisini, Bahadur Dhirendra, Srivastava Rohit
Department of Biosciences and Bioengineering, IIT Bombay, Powai, Mumbai 400076, India; Institute of Nano Science and Technology, Sector-64, Phase-10, Mohali 160062, India.
Department of Biosciences and Bioengineering, IIT Bombay, Powai, Mumbai 400076, India.
J Colloid Interface Sci. 2017 Jan 15;486:112-120. doi: 10.1016/j.jcis.2016.09.060. Epub 2016 Sep 28.
Hybrid nanoparticles with magnetic poly (lactide-co-glycolide) (PLGA) nanoparticle 'core', surface modified with folate-chitosan (fol-cht) conjugate 'shell' are evaluated as simultaneous anti-cancer therapeutic and MRI contrast agent. The fol-cht conjugate is prepared using carbodiimide crosslinking chemistry at an optimized folate to amine (chitosan) molar ratio for further coating on PLGA nanoparticles loaded with docetaxel and well packed super paramagnetic iron oxide nanoparticles (SPIONs). Apart from possessing a targeting moiety, the coating provides a physical barrier to avoid undesired burst release of drug and also imparts sensitivity to acidic pH, due to protonated amine group dependent decondensation of the coating and subsequent drug release. The biocompatible hybrid nanoparticles provide receptor targeted docetaxel and SPION delivery for anti-cancer therapy and magnetic resonance (MR) imaging respectively, as tested in both folate receptor positive and negative cancer cells. Enhancement in nanoparticle uptake by folate receptor positive oral cancer cells caused significant increase in docetaxel mediated cytotoxicity. While polymeric encapsulation and fol-cht coating negatively affects the magnetic property of iron oxide nanoparticles, their aggregation in the core, shortened the overall T relaxation time thereby enhancing the nanoparticle relaxivity to provide better in vitro MR imaging.
具有磁性聚（丙交酯-共-乙交酯）（PLGA）纳米颗粒“核”且表面用叶酸-壳聚糖（fol-cht）共轭物“壳”修饰的杂化纳米颗粒被评估为同时具有抗癌治疗作用和磁共振成像（MRI）造影剂。叶酸-壳聚糖共轭物是使用碳二亚胺交联化学方法，以优化的叶酸与胺（壳聚糖）摩尔比制备的，用于进一步包被负载多西他赛和充分填充的超顺磁性氧化铁纳米颗粒（SPIONs）的PLGA纳米颗粒。除了具有靶向部分外，该包衣还提供了一个物理屏障，以避免药物的意外突释，并且由于包衣中质子化胺基团依赖性的解聚以及随后的药物释放，赋予了对酸性pH的敏感性。在叶酸受体阳性和阴性癌细胞中进行测试时，这种生物相容性杂化纳米颗粒分别为抗癌治疗和磁共振（MR）成像提供了受体靶向的多西他赛和SPION递送。叶酸受体阳性口腔癌细胞对纳米颗粒摄取的增强导致多西他赛介导的细胞毒性显著增加。虽然聚合物包封和叶酸-壳聚糖包衣对氧化铁纳米颗粒的磁性有负面影响，但它们在核中的聚集缩短了整体T弛豫时间，从而提高了纳米颗粒的弛豫率，以提供更好的体外MR成像。
