Work

PSMA-specific degradable dextran for multiplexed immunotargeted siRNA therapeutics against prostate cancer

Year: 2022

Type: article

Abstract: Small interfering RNA (siRNA) is ideal for gene silencing through a sequence-specific RNA interference process. The redundancy and complexity of molecular pathways in cancer create a need for multiplexed targeting that can be achieved with multiplexed siRNA delivery. Here, we delivered multiplexed siRNA with a PSMA-targeted biocompatible dextran nanocarrier to downregulate CD46 and PD-L1 in PSMA expressing prostate cancer cells. The selected gene targets, PD-L1 and CD46, play important roles in the escape of cancer cells from immune surveillance. PSMA, abundantly expressed by prostate cancer cells, allowed the prostate cancer-specific delivery of the nanocarrier. The nanocarrier was modified with acid cleavable acetal bonds for a rapid release of siRNA. Cell imaging and flow cytometry studies confirmed the PSMA-specific delivery of CD46 and PD-L1 siRNA to high PSMA expressing PC-3 PIP cells. Immunoblot, qRT-PCR and flow cytometry methods confirmed the downregulation of CD46 and PD-L1 following treatment with multiplexed siRNA.

Source: Nanoscale

DOI: 10.1039/d2nr02200a

Authors: Zhihang Chen, Balaji Krishnamachary, Yelena Mironchik, Sangeeta Ray Banerjee, Martin G. Pomper, Zaver M. Bhujwalla

Institutions: Johns Hopkins University, Johns Hopkins Medicine

Language: English

Topic: RNA Interference and Gene Delivery

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Cancer Institute, National Institute of Biomedical Imaging and Bioengineering