Charge-selective fractions of naturally occurring nanoparticles as bioactive nanocarriers for cancer therapy

Abstract

A carnivorous fungus, Arthrobotrys oligospora, has been shown to secrete nanoparticles. In the present work, the potential of two charge-selective fractions of fungal nanoparticles (FNPs) as bioactive nanocarriers in cancer therapy is explored by investigating their immunostimulatory activities, cytotoxic mechanisms and in vitro immunochemotherapeutic effects. A surface charge-selective fractionation procedure to purify crude FNPs has been established, and two FNP fractions (i.e. FNP1 and FNP2), with different surface charges and similarly reduced diameters of 100–200nm, are obtained. Both FNP fractions enhance the secretion of multiple proinflammatory cytokines and chemokines from macrophages and splenocytes. However, FNP2 has stronger cytotoxicity than FNP1. It is FNP2 not FNP1 that could clearly inhibit cell proliferation by inducing apoptosis and arresting cells at the sub G0/G1 phase. Both the FNP fractions can form pH-responsive nanocomplexes with doxorubicin (DOX) via electrostatic interactions. For direct cytotoxicity, DOX–FNP2 complexes demonstrate higher activity than DOX against multiple tumor cells, while DOX–FNP1 complexes show weaker activity than DOX. Interestingly, in a co-culture experiment where splenocytes are co-cultured with tumor cells, both DOX–FNP complexes demonstrate higher cytotoxicity than DOX. In conclusion, this work proposes a combined therapeutics for cancer treatment using charge-selective fractions of FNPs as bioactive nanocarriers.