Nanoparticle‐Mediated siRNA Delivery and Multifunctional Modification Strategies for Effective Cancer Therapy

Abstract

method clinically, however, it is accompanied by the inevitable side effects on normal tissues. [9] Similarly, other treatment methods have failed to achieve satisfactory treatment results in clinic. With the discovery of key oncogenic markers and pathways, gene therapy has become a novel class of pharmaceutical drugs and shown significant therapeutic advantages in fighting cancer. [10][11][12] Compared with chemotherapy, gene therapy has better selectivity and specificity for related genes.RNA interference (RNAi) is an important defense mechanism of eukaryotic cells, which inhibits the expression or transcription of specific genes by blocking their translation or transcription, so it is considered to be a revolutionary tool for mediating gene therapy. [13][14][15] Previous research has shown that RNAi can effectively modulating the expression of any gene involved in tumor initiation, growth, and metastasis formation. [16][17][18] MicroRNA (miRNA), small interfering RNA (siRNA), and short hairpin RNA (shRNA) are the major types of RNAi molecules, which can mediate RNAi and cause mRNA cleavage. [19] miRNA is an endogenous single-stranded RNA, which mainly acts on the 3'-untranslated region of target genes in the RNAi pathway. [20] While siRNA is a double-stranded RNA (dsRNA) which can be transfected into the human body and act on any part of mRNA. [21] shRNA can be cloned into an expression vector and express siRNA. [22] siRNA has powerful specific RNAi triggering activity, so it shows great potential in nucleic acid therapy. [23] siRNA is a 20-25 base pair nucleic acid fragment that can degrade messenger RNA (mRNA) in the cytoplasm and interfere with the expression of specific genes. [24][25][26] The mechanism of siRNA-mediated RNAi action is shown in Figure 1. siRNA is synthesized and delivered into the cytoplasm, or generated by the endogenous Dicer-mediated dsRNA cleavage, then it can be incorporated into the RNA-induced silencing complex (RISC, a multi-protein complex). Then the sense strand (nonguiding strand) is cleaved by the Argonaute 2 (AGO2, an endonuclease of the RISC), while the antisense strand guides RISC toward the target mRNA with a complementary sequence, which is further cleaved by AGO2 into mRNA fragments. Subsequently, the mRNA fragments are degraded by cellular exonuclease. In addition, the antisense strand-RISC complex is capable of being recycled, so effectively preventing the translation of target mRNA into proteins.RNA interference (RNAi), which can inhibit the expression or transcription of specific genes, is considered to be a revolutionary tool for mediating gene therapy. Small interfering RNA (siRNA) is an important therapeutic agent for RNAi. However, the clinical application of siRNA-based gene silencing is still limited due to the easy degradation of siRNA during the circulation in the body and the difficulty in delivering siRNA to desired tissues and cells. The rapid development of nanotechnology provides new ideas for siRNA delivery and a large variety of nanocarriers have been d...

Injectable Optical System for Drug Delivery, Ablation, and Sampling in Deep Tissue

“…[4,5] These side effects are stimulating worldwide interest in the design of new therapeutic methodologies. [6][7][8][9][10][11][12] Photothermal therapy (PTT) is gaining tremendous attention in tumor treatment on account of its short treatment time, remarkable therapeutic efficacy, minor side effects on the human body, and synergistic effect with other cancer therapy strategies. [13][14][15][16][17] In principle, it allows photothermal agents to receive local hyperthermia under light irradiation to kill cancer cells in the tumor tissues.…”

“…[ 4,5 ] These side effects are stimulating worldwide interest in the design of new therapeutic methodologies. [ 6–12 ]…”

Efficient Treatment of Rheumatoid Arthritis by Degradable LPCE Nano-Conjugate-Delivered p65 siRNA

“…Further, the resulting cell death may attract more immune cells, thus ruining the whole treatment by elevating the immune response during RA. In addition, the large amounts of enzymes contained in lysosomes challenges the gene/vector complex with a high degradation risk, and this further prevents siRNAs from functioning [21]. For these reasons, siRNA-based RA gene therapy strategies are limited, despite the range of gene targets is widespread.…”

Lipid-coated albumin-paclitaxel nanoparticles loaded with sorcin-siRNA reverse cancer chemoresistance via restoring intracellular calcium ion homeostasis

“…How to successfully transport siRNA to tumor cells is a bottleneck for the application of siRNA in clinical practice. siRNA can be effectively protected from nuclease degradation by nanocarrier loading and can be enriched in the tumor by the enhanced permeability and retention (EPR) effect, and further, nano-carrier loading can also diminish immune stimulation [25].…”