Trigger-Responsive Gene Transporters for Anticancer Therapy

Abstract

In the current era of gene delivery, trigger-responsive nanoparticles for the delivery of exogenous nucleic acids, such as plasmid DNA (pDNA), mRNA, siRNAs, and miRNAs, to cancer cells have attracted considerable interest. The cationic gene transporters commonly used are typically in the form of polyplexes, lipoplexes or mixtures of both, and their gene transfer efficiency in cancer cells depends on several factors, such as cell binding, intracellular trafficking, buffering capacity for endosomal escape, DNA unpacking, nuclear transportation, cell viability, and DNA protection against nucleases. Some of these factors influence other factors adversely, and therefore, it is of critical importance that these factors are balanced. Recently, with the advancements in contemporary tools and techniques, trigger-responsive nanoparticles with the potential to overcome their intrinsic drawbacks have been developed. This review summarizes the mechanisms and limitations of cationic gene transporters. In addition, it covers various triggers, such as light, enzymes, magnetic fields, and ultrasound (US), used to enhance the gene transfer efficiency of trigger-responsive gene transporters in cancer cells. Furthermore, the challenges associated with and future directions in developing trigger-responsive gene transporters for anticancer therapy are discussed briefly.

Polydopamine-based nanoparticles with excellent biocompatibility for photothermally enhanced gene delivery

“…3 Since naked nucleic acids have poor internalization and the tendency for lysosomal degradation, non-viral carriers have been developed to compact genes and deliver them into target cells. [4][5][6] Nanoparticles, because of their unique properties, including adjustable size, morphology and surface characteristics, have been widely researched as non-viral gene carriers. [7][8][9][10] To realize satisfying gene transfection, non-viral gene delivery system must overcome various extracellular and intracellular barriers.…”

Gene therapy with RALA/iNOS composite nanoparticles significantly enhances survival in a model of metastatic prostate cancer

“…For example, replacement of the hydrophobic residues with hydrophilic rendered the resultant peptide (RGSG) incapable of transfection (Udhayakumar et al 2017 ). To date, RALA has successfully delivered plasmids encoding reporter genes (McCarthy et al 2014 ), mRNA (Udhayakumar et al 2017 ), siRNA (Bennett et al 2015 ), DNA vaccines (Rajendrakumar et al 2017 ), mRNA vaccines (Udhayakumar et al 2017 ) small molecules such as bisphosphonates (Massey et al 2016 ) and calcium-based bone substitutes (Huerta et al 2008 ) demonstrating broad utility.…”

“…The genetic origins of cancer render suitability for gene therapeutics such as small interfering RNAs, micro RNAs, and CRISPR gene editing tools (Rajendrakumar et al 2017 ). Indeed, previous research has reported abrogation of the growth of ZR-75-1 breast cancer xenografts when treated with RALA/pFKBPL (Bennett et al 2015 ), and the potency of RALA-delivered inducible nitric oxide synthase (iNOS) in a model of breast cancer metastasis.…”

Polymeric micelleplexes for improved photothermal endosomal escape and delivery of siRNA

“…Gene therapy has been regarded as a promising therapeutic approach for cancer, neurodegenerative diseases, and viral infections . However, naked nucleic acids require protection by carriers for delivery into target cells and obtain efficient gene expression or target protein silencing . Cellular uptake is the first step for internalization, and endocytosis is 1 of the major pathways for cellular uptake of nanosized nucleic acid delivery systems .…”