Current advancements in self-assembling nanocarriers-based siRNA delivery for cancer therapy

Abstract

Different therapeutic practices for treating cancers have significantly evolved to compensate and/or overcome the failures in conventional methodologies. The demonstrated potentiality in completely inhibiting the tumors and in preventing cancer relapse has made nucleic acids therapy (NAT)/gene therapy as an attractive practice. This has been made possible because NAT-based cancer treatments are highly focused on the fundamental mechanisms - i.e., silencing the expression of oncogenic genes responsible for producing abnormal proteins (via messenger RNAs (mRNAs)). However, the future clinical translation of NAT is majorly dependent upon the effective delivery of the exogenous nucleic acids (especially RNAs - e.g., short interfering RNAs (siRNAs) - herein called biological drugs). Moreover, nano-based vehicles (i.e., nanocarriers) are involved in delivering them to prevent degradation and undesired bioaccumulation while enhancing the stability of siRNAs. Herein, we have initially discussed about three major types of self-assembling nanocarriers (liposomes, polymeric nanoparticles and exosomes). Later, we have majorly reviewed recent developments in non-targeted/targeted nanocarriers for delivery of biological drugs (individual/dual) to silence the most important genes/mRNAs accountable for inducing protein abnormality. These proteins include polo-like kinase 1 (PLK1), survivin, vascular endothelial growth factor (VEGF), B-cell lymphoma/leukaemia-2 (Bcl-2) and multi-drug resistance (MDR). Besides, the consequent therapeutic effects on cancer growth, invasion and/or metastasis have also been discussed. Finally, we have comprehensively reviewed the improvements achieved in the cutting-edge cancer therapeutics while delivering siRNAs in combination with clinically approved chemotherapeutic drugs.

Keywords: Drug delivery; Gene therapy and cancer treatment; Nanocarriers; SiRNA.