A Synergistic Strategy Combining Chemotherapy and Photodynamic Therapy to Eradicate Prostate Cancer

Author:

Shirke Aditi A.1ORCID,Walker Ethan1ORCID,Chavali Sriprada2,Ramamurthy Gopalakrishnan3ORCID,Zhang Lifang3,Panigrahi Abhiram3ORCID,Basilion James P.13ORCID,Wang Xinning1ORCID

Affiliation:

1. Department of Biomedical Engineering, Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH 44106, USA

2. Department of Biochemistry, Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH 44106, USA

3. Department of Radiology, Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH 44106, USA

Abstract

Prostate cancer is the most prevalent cancer among men in the United States and is a leading cause of cancer-related death. Prostate specific membrane antigen (PSMA) has been established as a biomarker for prostate cancer diagnosis and treatment. This study aimed to develop a novel theranostic agent, PSMA-1-MMAE-Pc413, which integrates a PSMA-targeting ligand, the photosensitizer Pc413, and the microtubular inhibitor monomethyl auristatin E (MMAE) for synergistic therapeutic efficacy. In vitro uptake studies revealed that PSMA-1-MMAE-Pc413 demonstrated selective and specific uptake in PSMA-positive PC3pip cells but not in PSMA-negative PC3flu cells, with the uptake in PC3pip cells being approximately three times higher. In vitro cytotoxicity assays showed that, when exposed to light, PSMA-1-MMAE-Pc413 had a synergistic effect, leading to significantly greater cytotoxicity in PSMA-positive cells (IC50 = 2.2 nM) compared to PSMA-1-Pc413 with light irradiation (IC50 = 164.9 nM) or PSMA-1-MMAE-Pc413 without light irradiation (IC50 = 12.6 nM). In vivo imaging studies further demonstrated the selective uptake of PSMA-1-MMAE-Pc413 in PC3pip tumors. In in vivo studies, PSMA-1-MMAE-Pc413 dramatically improves the therapeutic outcome for prostate cancer by providing a synergistic effect that surpasses the efficacy of each treatment modality alone in PC3pip tumors. These findings suggest that PSMA-1-MMAE-Pc413 has strong potential for clinical application in improving prostate cancer treatment.

Funder

National Institute of Health

National Foundation of Cancer Research

Publisher

MDPI AG

Reference55 articles.

1. Epidemiology of Prostate Cancer;Rawla;World J. Oncol.,2019

2. Society, A.C. (2023). Facts & Figures 2023, American Cancer Society.

3. Jain, M.A., Leslie, S.W., and Sapra, A. (2024, March 10). Prostate Cancer Screening, StatPearls [Internet], Available online: https://www.ncbi.nlm.nih.gov/books/NBK556081/.

4. How aging of the global population is changing oncology;Gu;ecancermedicalscience,2021

5. Recent Advances in the Management of High-Risk Localized Prostate Cancer: Local Therapy, Systemic Therapy, and Biomarkers to Guide Treatment Decisions;McKay;Am. Soc. Clin. Oncol. Educ. Book.,2020

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