Nanocarriers for Delivery of siRNA and Co-Delivery of siRNA and Other Therapeutic Agents

Abstract

A major problem in cancer treatment is the multidrug resistance. siRNA inhibitors have great advantages to solve the problem, if the bottleneck of their delivery could be well addressed by the various nanocarriers. Moreover, co-delivery of siRNA together with the various anticancer agents in one nanocarrier may maximize their additive or synergistic effect. This review provides a comprehensive summary on the state-of-the-art of the nanocarriers, which may include prodrugs, micelles, liposomes, dendrimers, nanohydrogels, solid lipid nanoparticles, nanoparticles of biodegradable polymers and nucleic acid nanocarriers for delivery of siRNA and co-delivery of siRNA together with anticancer agents with focus on synthesis of the nanocarrier materials, design and characterization, in vitro and in vivo evaluation, and prospect and challenges of nanocarriers.

The delivery of therapeutic oligonucleotides

“…Although they have not progressed clinically to the same degree as LNPs, it is worth noting that the first use of siRNA to treat human cancer involved a ligand-targeted cyclodextrin-based polymeric nanoparticle (192). Excellent recent reviews provide comprehensive accounts of the numerous publications utilizing this general approach to oligonucleotide delivery (193,194). …”

“…A virtue of many polymeric nanocarriers is their ready ability to convey both an oligonucleotide and a small molecule drug; this is especially interesting in the context of cancer chemotherapy. Thus there are several promising reports of in vivo co-delivery of siRNA and anticancer drugs (194,197,198). …”

“…This would include formation of nanoscale polyplexes involving CPPs (202,203), cationic dendrimers such as PAMAMs (194,204) or linear or cross-linked PEI (205). …”

Application of nanotechnology to cancer radiotherapy

“…By screening an siRNA library targeting all protein kinases and E3 ubiquitin ligases in the human genome, TRAF2 (TNF receptor-associated factor 2) was recognized as an effective target for siRNA silencing, which resulted in growth suppression of glioblastoma cells and sensitization of these radioresistant cells to radiotherapy (Zheng et al 2008). However, the clinical use of siRNA is hindered by its sensitivity to enzymatic degradation, fast clearance, immunogenicity and incapability of entering cells (Zhao and Feng 2015). Therefore, formulation of siRNA into nanoparticles is a practical way to achieve the function of siRNA.…”

Arany és ezüst nanorészecskék sejtbiológiai hatásainak vizsgálata p53 deficiens rákos sejtekben és tumor metasztázis modellben

“…Nanorészecskék segítségével terápiás nukleinsavak célba juttatása is megvalósítható. Ilyen esetekben kis RNS molekulákat kötnek a nanorészecskék felszínére, melyek célgénjeik csendesítésén keresztül képesek befolyásolni a rákos sejtek génexpressziós tulajdonságait [122]. A terápiás molekulák kötésén kívül azonban számos egyéb csoporttal is funkcionalizálhatunk nano-hordozókat, melyek elősegíthetik a kemoterápiás hatóanyagok célzott irányítását a rákos sejtekbe, így megnövelve a tumorterápia specifikusságát.…”