“Drug-Free” chitosan nanoparticles as therapeutic for cancer treatment

Abstract

Chitosan is cancer cytotoxic. It induces apoptosis/necrosis/autophagy and immuno-responses, and mitigates angiogenic and metastasis tendency of cancer cells. The lower molecular weight chitosan induces apoptosis, whereas the higher molecular weight chitosan exerts apoptosis and necrosis. Transforming chitosan into nanoparticles raises its anti-cancer efficacy with mode of cancer cell death governed by particle size to a greater extent than chitosan molecular weight. The larger nanoparticles tend to exert apoptosis. The smaller nanoparticles mediate necrosis. “Drug-free” small nanoparticles constituted of lower molecular weight chitosan are more cytotoxic than those of larger chitosan molecules/particles in vitro and in vivo, with no clear relationship between the deacetylation degree and zeta potential of nanoparticulate chitosan with anti-cancer activity. “Drug-free” chitosan nanoparticles are potentially as viable as the drug-loaded chitosan nanoparticles but with reduced systemic adverse effects. Their anti-cancer efficacy can be modulated through particle dose adjustment with lower risks of harmful effects than drugs and without processing hurdles faced in the development of drug-loaded chitosan nanoparticles such as low aqueous drug solubility, poor drug encapsulation, premature drug release and drug absorption, and drug instability with toxic metabolite formation.