Environment‐Responsive Lipid/siRNA Nanoparticles for Cancer Therapy

Abstract

RNA interference (RNAi) is a promising technology to regulate oncogenes for treating cancer. The primary limitation of siRNA for clinical application is the safe and efficacious delivery of therapeutic siRNA into target cells. Lipid‐based delivery systems are developed to protect siRNA during the delivery process and to facilitate intracellular uptake. There is a significant progress in lipid nanoparticle systems that utilize cationic and protonatable amino lipid systems to deliver siRNA to tumors. Among these lipids, environment‐responsive lipids are a class of novel lipid delivery systems that are capable of responding to the environment changes during the delivery process and demonstrate great promise for clinical translation for siRNA therapeutics. Protonatable or ionizable amino lipids and switchable lipids as well as pH‐sensitive multifunctional amino lipids are the presentative environment‐responsive lipids for siRNA delivery. These lipids are able to respond to environmental changes during the delivery process to facilitate efficient cytosolic siRNA delivery. Environment‐responsive lipid/siRNA nanoparticles (ERLNP) are developed with the lipids and are tested for efficient delivery of therapeutic siRNA into the cytoplasm of cancer cells to silence target genes for cancer treatment in preclinical development. This review summarizes the recent developments in environment‐response lipids and nanoparticles for siRNA delivery in cancer therapy.

Emerging role of exosomes in cancer progression and tumor microenvironment remodeling

“…Small interfering RNAs (siRNAs) are double-stranded RNA molecules of up to 25 nucleotides in length. They are produced from mRNA and lncRNAs via the function of the RNase III enzyme Dicer [ 422 ]. The actual function of siRNA is achieved it is incorporated into the RNA-induced silencing complex (RISC) to direct the RNAi machinery to target mRNA for degradation after complementary sequences are found.…”

Genetic Variants in Transcription Factor Binding Sites in Humans: Triggered by Natural Selection and Triggers of Diseases

“…In the process of functional validation, overexpression and knockdown experiments are necessary to decipher the biological roles of identified target genes in diseases [56]. The most commonly utilized techniques are RNA activation (RNAa) [57] and RNA interference (RNAi) [58]. CRISPR activation (CRISPRa) and CRISPR interference (CRISPRi) screening are alternative gene-editing approaches [50,51].…”

Overcoming Barriers: Clinical Translation of siRNA Nanomedicines

“…Further detail on different cationic, ionizable and helper lipids that can be utilized for siRNA delivery have been covered in a recent review by Lu et al. [ 67 ]…”