Progress in Delivery of siRNA-Based Therapeutics Employing Nano-Vehicles for Treatment of Prostate Cancer

Abstract

Prostate cancer (PCa) accounts for a high number of deaths in males with no available curative treatments. Patients with PCa are commonly diagnosed in advanced stages due to the lack of symptoms in the early stages. Recently, the research focus was directed toward gene editing in cancer therapy. Small interfering RNA (siRNA) intervention is considered as a powerful tool for gene silencing (knockdown), enabling the suppression of oncogene factors in cancer. This strategy is applied to the treatment of various cancers including PCa. The siRNA can inhibit proliferation and invasion of PCa cells and is able to promote the anti-tumor activity of chemotherapeutic agents. However, the off-target effects of siRNA therapy remarkably reduce its efficacy in PCa therapy. To date, various carriers were designed to improve the delivery of siRNA and, among them, nanoparticles are of importance. Nanoparticles enable the targeted delivery of siRNAs and enhance their potential in the downregulation of target genes of interest. Additionally, nanoparticles can provide a platform for the co-delivery of siRNAs and anti-tumor drugs, resulting in decreased growth and migration of PCa cells. The efficacy, specificity, and delivery of siRNAs are comprehensively discussed in this review to direct further studies toward using siRNAs and their nanoscale-delivery systems in PCa therapy and perhaps other cancer types.

miR‐21 inhibition reverses doxorubicin‐resistance and inhibits PC3 human prostate cancer cells proliferation

“…The expression highly of PTEN in many malignancies has been linked with circumventing of MDR and the elevated reaction of resistance cells to antineoplastic drugs through repression of PI3K/Akt molecular cascade (Mashayekhi et al., 2019; Shen et al., 2016). Repressing the PI3K/Akt axis with LY294002 or Akt siRNA (si‐Akt) could retrieve drug sensitivity by downregulating the expression of P‐gp and MRP1 (Ashrafizadeh et al., 2020). Lately, reported that miR‐21 attenuates PTEN expression and augments proliferation and invasion of the LIHC cells (Tomimaru et al., 2010).…”

Engineered Microneedle Patches for Controlled Release of Active Compounds: Recent Advances in Release Profile Tuning

“…Another advantage of controlled drug release is improved patient compliance due to less frequent drug administration. [ 41–43 ] Microneedles may be classified into three categories based on their release profiles: burst release, prolonged release, and on‐demand release. Rapid drug release from polymeric systems is coined “burst or instant release.” [ 44 ] This kind of release is necessary for applications such as analgesic delivery, when rapid release of a therapeutic agent is essential.…”

Nano-Assemblies from Amphiphilic PnBA-b-POEGA Copolymers as Drug Nanocarriers

“…The unique core-shell architecture of AmBC nanoassemblies enables a physical encapsulation of drug molecules into their hydrophobic micellar core, conferring an enhanced drug solubility and reduced toxicity. The hydrophilic shell stabilizes the core, ameliorates drug pharmacokinetics, and facilitates drug accumulation in tumors through the enhanced permeability and retention (EPR) effect [ 13 , 14 ].…”