The anti-tumor efficacy of nanoparticulate form of ICD-۸۵ versus free form

Biodegradable polymeric nanoparticles (NPs) have been intensively studied as a possible way to enhance anti-tumor efficacy while reducing side effects. ICD-۸۵, derived from the venom of two separate species of venomous animals, has been shown to exhibit anti-cancer activity. In this report polymer based sodium alginate nanoparticles of ICD-۸۵ was used to enhance its therapeutic effects and reduce its side effects. The inhibitory effect was evaluated by MTT assay. The necrotic effect was assessed using LDH assay. The induction of apoptosis was analyzed by caspase-۸ colorimetric assay kit. Cytotoxicity assay in HeLa cells demonstrated enhanced efficacy of ICD-۸۵ loaded NPs compared to the free ICD-۸۵. The IC۵۰ values obtained in HeLa cells after ۴۸ h, for free ICD-۸۵ and ICD-۸۵ loaded NPs were ۲۶±۲.۹μg ml-۱ and ۱۸±۲.۵μg ml-۱, respectively. While it was observed that free ICD-۸۵ exhibits mild cytotoxicity towards normal MRC-۵ cells (IC۵۰>۶۰µg ml-۱), ICD-۸۵ loaded NPs was found to have higher efficacy in anti-proliferative activity on HeLa cells in vitro without any significant cytotoxic effect on normal MRC-۵ cells. The apoptosis-induction mechanism by both form of ICD-۸۵ on HeLa cells was found to be through activation of caspase-۸ with approximately ۲ fold greater of ICD-۸۵ loaded NPs as compared to free ICD-۸۵. Our work reveals that although ICD-۸۵ in free form is relatively selective to inhibit the growth of cancer cells via apoptosis as compared to normal cells, but nanoparticulate form increases its selectivity towards cancer cells.

کلیدواژه ها:

ICD ، ۸۵ ، sodium alginate ، Nanoparticle ، Necrotic effect ، Apoptosis