Second-generation aptamer-conjugated PSMA-targeted delivery system for prostate cancer therapy

Area of Science:

• Biotechnology
• Nanomedicine
• Oncology

Background:

• MicroRNA (miR)-15a and miR-16-1 function as tumor suppressors in prostate cancer.
• Effective delivery of these miRNAs to cancer cells is crucial for therapeutic success.
• Prostate-specific membrane antigen (PSMA) is a target for prostate cancer therapy, with aptamer A10-3.2 showing high binding efficiency.

Purpose of the Study:

• To develop a targeted delivery system for miR-15a and miR-16-1 to prostate cancer cells.
• To utilize the PSMA-targeting aptamer A10-3.2 for enhanced delivery.
• To evaluate the efficacy of a polyamidoamine (PAMAM)-based vector for miRNA delivery.

Main Methods:

• A PSMA-targeting RNA aptamer (A10-3.2) was conjugated to polyamidoamine (PAMAM) nanoparticles using polyethylene glycol (PEG) as a spacer, creating a PAMAM-PEG-APT complex.
• This complex served as a vector for delivering microRNA (miR-15a and miR-16-1) to prostate cancer cells.
• Transfection efficiency and cell viability assays were performed using PSMA-positive (LNCaP) and PSMA-negative (PC3) cell lines.

Main Results:

• The synthesized DNA/PAMAM-PEG-APT complex exhibited higher transfection efficiency compared to the DNA/PAMAM-PEG complex in both cell lines.
• In PSMA-positive LNCaP cells, the miRNA/PAMAM-PEG-APT formulation showed a 4.7-fold lower IC50 value than the miRNA/PAMAM-PEG formulation at a N/P ratio of 15:1, indicating enhanced cell killing.
• The targeted system demonstrated superior delivery and therapeutic potential in PSMA-expressing prostate cancer cells.

Conclusions:

• The developed PSMA-targeted PAMAM-based vector effectively delivers therapeutic microRNAs to prostate cancer cells.
• This targeted delivery system enhances therapeutic efficacy and allows for selective killing of PSMA-positive prostate cancer cells.
• The system holds promise for widening the therapeutic window in prostate cancer treatment.