Functionalized non-viral cationic vectors for effective siRNA induced cancer therapy

Abstract

RNA interference (RNAi) has been regarded as a vital asset in the field of therapeutics as it has the capability to silence various disease causing genes including those that cause cancer. Small non-coding RNA molecules such as short interfering RNAs (siRNAs) are one of the extensively studied RNAi inducers for gene modulations. However, the delivery of RNAi inducers including siRNAs is compromised due to the barriers imposed by the biological system such as degradation by nucleases, rapid clearance, high anionic charge, immunogenicity and off-target effects. Viral vectors, in general exhibit high transfection efficiencies but are expensive and likely to confer immunological and safety issues. Therefore, non-viral cationic vectors (NVCVs) have received considerable attention to not only address these issues but also for developing efficacious siRNA delivery vectors. In this review, we will first discuss the historical development of various NVCVs and then will discuss functionalized NVCVs with linkers that provide stability, as well as respond to the cancer cell environment and with cancer cell receptor specific ligands to explicitly target them for improved siRNA efficacy. Multifunctional NVCVs (MNVCVs) that employ multiple synergistically working components to aid siRNA delivery efficacy are also discussed.

Poly (1-Vinyl Imidazole) Polyplexes as Novel Therapeutic Gene Carriers for Lung Cancer Therapy

“…The cells were first treated with the polyplex for 4 h followed which the medium was replaced, and different concentrations of 5-FU were added, and the viability was determined after 48 h. Imidazole and its derivatives have been earlier shown to inhibit migration of cancer cells and also their invasiveness. 27 Our results show that PVI also with its multiple imidazole groups can retard the migration of A549 cancer cells. It is observed that the cell viability of A549 lung cancer cells decreased when pre-treated with polyplex for 4 h followed by treatment with 5-FU for 48 h. The free 5-FU exhibited a decrease in cell viability by 77% at 400 M concentration while free si-RNA reduced the viability to 80% at 100 nM concentration.…”

Poly(1-vinylimidazole) polyplexes as novel therapeutic gene carriers for lung cancer therapy

“…The cells were first treated with the polyplex for 4 h after which the medium was replaced. Different concentrations of 5-FU were added, and the viability was determined after 48 h. Imidazole and its derivatives have been earlier shown to inhibit the migration and the invasiveness of cancer cells [32]. Our results show that also PVI with its multiple imidazole groups can retard the migration of A549 cancer cells.…”