Study on the prostate cancer-targeting mechanism of aptamer-modified nanoparticles and their potential anticancer effect in vivo

Abstract

Ligand-mediated prostate cancer (PCa)-targeting gene delivery is one of the focuses of research in recent years. Our previous study reported the successful preparation of aptamer-modified nanoparticles (APT-NPs) in our laboratory and demonstrated their PCa-targeting ability in vitro. However, the mechanism underlying this PCa-targeting effect and their anticancer ability in vivo have not yet been elucidated. The objective of this study was to assess the feasibility of using APT-NPs to deliver micro RNA (miRNA) systemically to PCa cells, to testify their tumor-targeting efficiency, and to observe their biodistribution after systemic administration to a xenograft mouse model of PCa. In addition, the effect of APT depletion and endocytosis inhibitors on cellular uptake was also evaluated quantitatively in LNCaP cells to explore the internalization mechanism of APT-NPs. Finally, blood chemistry, and renal and liver function parameters were measured in the xenograft mouse model of PCa to see whether APT-NPs had any demonstrable toxicity in mice in vivo. The results showed that APT-NPs prolonged the survival duration of the PCa tumor-bearing mice as compared with the unmodified NPs. In addition, they had a potential PCa-targeting effect in vivo. In conclusion, this research provides a prototype for the safe and efficient delivery of miRNA expression vectors to PCa cells, which may prove useful for preclinical and clinical studies on the treatment of PCa.

Armored long non-coding RNA MEG3 targeting EGFR based on recombinant MS2 bacteriophage virus-like particles against hepatocellular carcinoma

“…After treatment with chlorpromazine, the MEG3 mRNA level decreased to 37.67% ± 12.31%, compared with the untreated group (Figure 4D ), indicating that clathrin-mediated endocytosis was involved in cellular entry of GE11-VLPs. After treatment with colchicine, a specific inhibitor of micropinocytosis [ 41 , 42 ], and the MEG3 mRNA level decreased to 56.08% ± 6.74% of controls (Figure 4D ). Following treatment with both chlorpromazine and colchicine, cellular entry of GE11-VLPs was strongly inhibited, and was reduced to approximately 20%.…”

Targeting Inflammasome Activation in COVID-19: Delivery of RNA Interference-Based Therapeutic Molecules

“…Dendrimers are large, branched polymers that interact with different molecules via covalent conjugation, encapsulation, and electrostatic interactions. Polyamidoamine (PAMAM) is among the most widely studied dendrimers and has been shown to be an effective vehicle for targeted delivery of miRNAs upon modification with an aptamer [ 173 , 201 ].…”