Rationally designed oxaliplatin-nanoparticle for enhanced antitumor efficacy
作者： Abhimanyu Paraskar , Shivani Soni , Bhaskar Roy , Anne-Laure Papa , Shiladitya Sengupta
DOI: 10.1088/0957-4484/23/7/075103
关键词:
摘要: Nanoscale drug delivery vehicles have been extensively studied as carriers for cancer chemotherapeutics. However, the formulation of platinum chemotherapeutics in nanoparticles has a challenge arising from their physicochemical properties. There are only few reports describing oxaliplatin nanoparticles. In this study, we derivatized monomeric units polyisobutylene maleic acid copolymer with glucosamine, which chelates trans-1,2-diaminocyclohexane (DACH) platinum?(II) through novel monocarboxylato and O???Pt coordination linkage. At specific polymer to ratio, complex self-assembled into nanoparticle, where polymeric act leaving group, releasing DACH?platinum sustained pH-dependent manner. Sizing was done using dynamic light scatter electron microscopy. The were evaluated efficacy in?vitro in?vivo. Biodistribution quantified inductively coupled plasma atomic absorption spectroscopy (ICP-AAS). PIMA?GA?DACH?platinum nanoparticle found be more active than free in?vitro. In?vivo, resulted greater tumor inhibition (equivalent 5?mg?kg?1 dose) minimal nephrotoxicity or body weight loss. ICP-AAS revealed significant preferential accumulation reduced biodistribution kidney liver following administration compared oxaliplatin. These results indicate that rational engineering inspired by bioactivation increased antitumor potency systemic toxicity parent cytotoxic. Rational design can emerge an exciting strategy synthesis nanomedicines chemotherapy.
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