Folate-targeted amphiphilic cyclodextrin.siRNA nanoparticles for prostate cancer therapy exhibit PSMA mediated uptake, therapeutic gene silencing in vitro and prolonged circulation in vivo

Recent Advances in Nanomaterials for Gene Delivery—A Review

“…However, in the same study no significant difference in siRNA delivery was observed between PEGylated-CD.siRNA and CD.siRNA [116]. Evans et al [117] designed a CD.siRNA-DSPE-PEG 5000 -folate nanoparticle to determine the gene silencing ability in prostate cancer cell lines. Prostate-specific membrane antigen (PSMA) is upregulated in prostate cancer, and its expression increases as the cancer metastasizes.…”

“…Incorporation of DSPE-PEG5000 was utilized to reduce the overall cationic charge of the particle to limit clearance by RES system. Three different formulations of cyclodextrin complexed with siRNA were used (Figure 6): CCD (cationic amphiphilic cyclodextrin /siRNA), CD-M (Cyclodextrin/siRNA-DSPE-PEG 5000 -methyl) and CD-F (Cyclodextrin/siRNA-DSPE-PEG 5000 -folate), and their gene delivery and targeting uptake potentials were assessed in PSMA-positive and PSMA-negative cells [117]. The CD-F formulation resulted in increased targeted uptake and gene delivery potential in PSMA-positive cells (VCaP and LNCaP) compared to CD-M.…”

“…The CD-F formulation resulted in increased targeted uptake and gene delivery potential in PSMA-positive cells (VCaP and LNCaP) compared to CD-M. Yet, when cells were pretreated with excess folate, CD-F resulted in reduced cellular uptake, while no significant change in uptake in untreated vs. folate-pretreated cells was observed for CD-M, indicating that the free folate competed with CD-F for targeted uptake [117]. Overall it was demonstrated how folate could be used both as a targeting ligand and as a method to increase cellular uptake.…”

“…Insets show enlarged images at greater resolution. Figures reproduced with permission from [117]. Copyright Elsevier, 2016.…”

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. 18 Natural cationic polymer chitosan (CS) has been widely used in gene delivery vectors because of its good biocompatibility, biodegradability and low toxicity, amongst other advantages. [14][15][16][17] Therefore, it is necessary to identify a safe and effective siRNA delivery vector to effectively delivery siRNA into tumor cells.…”