Nanoparticle Engineering Enhances Anticancer Efficacy of Andrographolide in MCF-7 Cells and Mice Bearing EAC

Partha      Roy; Suvadra      Das; Anushree      Mondal; Urmi      Chatterji; Arup      Mukherjee

Abstract

Success in cancer chemotherapy relies on efficient delivery of anti-neoplastic drugs, with minimal side-effects on non-cancerous cells. Nanoparticulation of prospective anti-cancer drugs, that were deemed unsuitable due to short biological half life, poor water solubility and low cellular permeability, has been hypothesized to generate superior chemotherapeutic agents, leading to reduced non-specific action and fewer side-effects. In lieu of the above, different synthetic modulations on the putative anti-cancer compound andrographolide (AG) were explored to improve its therapeutic efficiency. Our results indicated that PLGA-nanoparticulation of andrographolide diterpenoid enhanced its anti-cancer properties three fold. Chitosan coating of AG nanoparticles further accentuated cellular localization, induced G1 cell cycle arrest and increased cellular toxicity and apoptosis in MCF-7 cells. The charge modulated nanoparticles were seen to traverse more efficiently through the cytoplasm and accumulate in the nucleus, thus enhancing their anti-proliferative efficacy. In vivo studies confirm that the nanoparticles reduced tumor weight by 68.21% as compared to 24.7% by AG, and increased the life span of mice infected with Ehrlich ascites carcinoma (EAC) by 78.08% as compared to 23.5% for AG alone. This was achieved through development of slow release-type nanoparticle cargo delivery devices, and enhanced the efficiency of AGnps for targeting cancer cells. AG nanoparticles also showed sufficient promise as safe anti-cancer drugs since they had minimal impact on animal hematology. Hence, we successfully prepared non-toxic and delivery-efficient andrographolide nanoparticles, and established for the first time that PLGA-nanoparticulation of andrographolide and additional chitosan coating increased its anti-cancer efficacy in human breast cancer cells and mouse EAC model.

Keywords: Andrographolide, apoptosis, chitosan, Ehrlich Ascites Carcinoma, G1 cell cycle arrest, human breast cancer cells, nanoparticles, therapeutic efficiency, anti-cancer drugs, targeting cancer cells