Nano-based delivery of RNAi in cancer therapy

Abstract

BackgroundRNA interference (RNAi), a newly developed method in which RNA molecules inhibit gene expression, has recently received considerable research attention. In the development of RNAi-based therapies, nanoparticles, which have distinctive size effects along with facile modification strategies and are capable of mediating effective RNAi with targeting potential, are attracting extensive interest.ObjectiveThis review presents an overview of the mechanisms of RNAi molecules in gene therapy and the different nanoparticles used to deliver RNAi molecules; briefly describes the current uses of RNAi in cancer therapy along with the nano-based delivery of RNA molecules in previous studies; and highlights some other carriers that have been applied in clinical settings. Finally, we discuss the nano-based delivery of RNAi therapeutics in preclinical development, including the current status and limitations of anti-cancer treatment.ConclusionWith the growing number of RNAi therapeutics entering the clinical phase, various nanocarriers are expected to play important roles in the delivery of RNAi molecules for cancer therapeutics.

Advances in treatment formulations for acute myeloid leukemia

“…There are few antisense oligonucleotides on the market, probably because of a lack of stability in blood circulation, inefficient intracellular delivery, difficulties in targeting cells or tissues, and poor affinity with the target sequence [65]. Therefore, as part of cancer treatment strategies, different NPs were designed to improve either the stability in the blood stream or their ability to target cancer cells [66]. Hundreds of Phase 1, 2, and 3 clinical trials for cancer indications are ongoing [67].…”

Rekindling RNAi Therapy: Materials Design Requirements for In Vivo siRNA Delivery

“…Metallic vehicles (primarily gold or iron oxide nanoparticles) for siRNA tend to underperform in vivo based on measurements of gene silencing efficiency, with average efficiencies of 72.3 ± 16.3% in vitro and 54.7 ± 19.6% in vivo (Table and Figure ). This trend may be attributed to the solid structure of the constructs, which leads to formulations in which the siRNA payloads are covalently bound or chemically adhered to the surface of the particles (e.g., thiol‐gold chemistry) . This surface‐loading mechanism leaves the siRNA molecules exposed to the degrading conditions of the in vivo environment during circulation, which underscores the necessity for an siRNA‐protective design; thus, metallic systems generally employ cationic polymer/lipid coatings to facilitate loading and protection of the siRNA payload …”

“…Active targeting, via the agency of a pendant molecular species that has some affinity for the tumor, showed a minor improvement over EPR‐mediated particle accumulation. However, in other (non‐tumor) animal disease models, the use of selective homing agents can generate more substantial accumulation of siRNA . For applications beyond local administration and passive MPS‐mediated homing to clearance organs (e.g., liver, lungs, spleen), the literature contains a wide variety of homing moieties that can be decorated on the surface of carrier particles for in vivo targeting, including aptamers and receptor‐specific ligands .…”

Co‐delivery of hypoxia inducible factor‐1α small interfering RNA and 5‐fluorouracil to overcome drug resistance in gastric cancer SGC‐7901 cells

“…[11][12][13] Accordingly, it can be used to down-regulate the expression of drug resistance proteins and reverse MDR in cancer cells. [11][12][13] Accordingly, it can be used to down-regulate the expression of drug resistance proteins and reverse MDR in cancer cells.…”

“…Small interfering RNA (siRNA) can initiate the degradation of complementary mRNA molecules to produce a therapeutic effect. [11][12][13] Accordingly, it can be used to down-regulate the expression of drug resistance proteins and reverse MDR in cancer cells. However, the delivery of siRNA is a challenge because of its sensitivity to nuclease, poor cell uptake, limited blood stability and poor transport to targeted sites, which all limit the application of siRNA.…”