Cancer therapeutics strategy using nano-carrier mediated natural drugs

Abstract

Nucleolin is a multifactorial protein, having a significant role in chromatin remodelling, mRNA stability, ribosome biogenesis, stemness, angiogenesis, etc., thus, it is potential therapeutic target in cancer. The purpose of this paper is to study porous silicon (pSi) nanocarrier-based natural drug delivery system targeting dysregulated nucleolin expression for cancer therapeutics. Quercetin was loaded in pre-synthesized and characterized pSi nanoparticles, and release kinetics was studied. The study compared the inhibitory concentration (IC50) of quercetin, synthetic drug doxorubicin, and quercetin-loaded pSi nanoparticles. Further, mRNA expression of a target gene, nucleolin, was tested with a quercetin treated breast cancer cell line (MCF-7). Quercetin-loaded pSi nanoparticles followed first-order release kinetics. IC50 was determined at concentrations of 312 nM, 160 µM, and 50 µM against doxorubicin, quercetin, and quercetin-loaded pSi nanoparticles, respectively. The results further indicated 16-fold downregulation of nucleolin mRNA expression after 48h of quercetin treatment of exponentially growing MCF-7 cells. Whether pSi nanoparticle loaded quercetin can significantly downregulate nucleolin protein expression and its impact on apoptosis, cell proliferation, and angiogenic pathways need further investigation. The practical application of the proposed nanocarrier-based drug delivery system potentially lays out a path for developing targeted therapy against nucleolin-dysregulated cancer using natural products to minimize the side effects of conventional chemotherapeutic drugs. Inhibition of nucleolin and nucleolin regulated pathways using natural compounds and its targeted delivery with nanocarrier is not yet done.