Targeted polymeric nanoparticles for cancer gene therapy

Abstract

In this article, advances in designing polymeric nanoparticles for targeted cancer gene therapy are reviewed. Characterization and evaluation of biomaterials, targeting ligands, and transcriptional elements are each discussed. Advances in biomaterials have driven improvements to nanoparticle stability and tissue targeting, conjugation of ligands to the surface of polymeric nanoparticles enable binding to specific cancer cells, and the design of transcriptional elements has enabled selective DNA expression specific to the cancer cells. Together, these features have improved the performance of polymeric nanoparticles as targeted non-viral gene delivery vectors to treat cancer. As polymeric nanoparticles can be designed to be biodegradable, non-toxic, and to have reduced immunogenicity and tumorigenicity compared to viral platforms, they have significant potential for clinical use. Results of polymeric gene therapy in clinical trials and future directions for the engineering of nanoparticle systems for targeted cancer gene therapy are also presented.

Systemic RALA/iNOS Nanoparticles: A Potent Gene Therapy for Metastatic Breast Cancer Coupled as a Biomarker of Treatment

“…Likewise, RRx-001, which preferentially releases ·NO in a hypoxic environment, attenuated murine squamous cell carcinoma (SCC) VII xenograft growth and sensitized to fractionated radiotherapy, doubling the survival time of mice 29 . Ligand targeting of nanoparticles is a common targeting strategy, with tumor-associated dysregulated expression of the receptors of transferrin, folic acid, epidermal growth factor, and hyaluronic acid being particularly popular 30 . We have previously employed numerous transcriptional targeting strategies.…”

Antibody-Targeted Nanoparticles for Cancer Treatment

“…Ab-targeted NP delivery vectors such as polymeric NPs [93], AuNPs [94] and liposomes are also beginning to find a role in delivery of nucleic acids for cancer therapy. This provides opportunity for the delivery of DNA to induce expression of therapeutic tumour suppressor genes, or delivery of small interfering RNA (siRNA) or anti-sense DNA sequences which can disrupt the translation of oncogenes [95].…”

Gene delivery nanoparticles to modulate angiogenesis

“…Non-canonical peptide motifs with affinity to specific surface receptors, such as apo-transferrin on glioma capillary endothelial cells [43], integrin on endothelial cells [44], and prohibitin on adipocytes [45], have been identified via phage display and computational approaches, the use of which is also of particular interest in the field of nanoparticle targeting. Finally, other features of a gene delivery nanoparticle, such as the promoter on delivered plasmid DNA, can also drive cellular and tissue targeting [46]. Various non-viral gene delivery vectors shown in Figure 3 have been investigated with their standard structures and also in modified forms for enhanced non-viral gene delivery to various targets, including endothelial cells to modulate angiogenesis.…”