Co‐delivery of oncolytic virus and chemotherapeutic modality: Vincristine against prostate cancer treatment: A potent viro‐chemotherapeutic approach

• Published in: Journal of medical virology 2024-07, Vol.96 (7), p.e29748-n/a
• Main Authors: Anjum, Sadia, Naseer, Faiza, Ahmad, Tahir, Liaquat, Afrose, Abduh, Maisa S., Kousar, Kousain
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacology; Antitumor activity; Cancer therapies; CD44 antigen; Cell cycle; Cell death; Cell Line, Tumor; Cell Survival - drug effects; Cell viability; Chemotherapy; Controlled release; Cytotoxicity; Design optimization; Drug Delivery Systems; Flow cytometry; Humans; hyaluronic acid; Male; Measles virus - drug effects; Membrane potential; nanoparticles; Nanoparticles - chemistry; Oncolysis; Oncolytic Virotherapy - methods; Oncolytic Viruses; PC-3 Cells; Polydispersity; Prostate cancer; Prostate carcinoma; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - therapy; S phase; Sustained release; Tumor cell lines; Vincristine; Vincristine - administration & dosage; Vincristine - pharmacology; Viruses; Zeta potential
• ISSN: 0146-6615; 1096-9071; 1096-9071
• DOI: 10.1002/jmv.29748

Prostate cancer is a prevalent carcinoma among males, and conventional treatment options are often limited. Cytotoxic chemotherapy, despite its drawbacks, remains a mainstay. We propose a targeted co‐delivery approach using nanoscale delivery units for Oncolytic measles virus (OMV) and vincristine (VC) to enhance treatment efficacy. The HA‐coated OMV + VC‐loaded TCs nanoformulation is designed for targeted oncolytic activity in prostate cancer. The CD44 expression analysis in prostate cancer cell lines indicates a significantly high expression in PC3 cells. The optimization of nanoformulations using Design of Expert (DOE) is performed, and the preparation and characterization of HA‐coated OMV + VC‐loaded TCs nanoformulations are detailed showing average particle size 397.2 ± 0.01 nm and polydispersity index 0.122 with zeta potential 19.7 + 0.01 mV. Results demonstrate successful encapsulation efficiency with 2.4 × 106 TCID50/Ml and sustained release of OMV and VC from the nanoformulation for up to 72 h. In vitro, assays reveal potent anticancer activity at 10 ± 0.71% cell viability in PC3 cells compared to 73 ± 0.66% in HPrEC and significant morphological changes at 90 µg/ml in dose and time‐dependent manner. The co‐formulation showed positive cell death 49.5 ± 0.02% at 50 µg PI/ml in PBS and 54.3% cell cycle arrest at the G2/M phase, 8.1% G0/G1 and 5.7% at S phase, with significant mitochondrial membrane potential (MMP) at 50 µg/ml, as assessed by flow cytometry (FACS). The surface‐integrating ligand approach enhances the targeted delivery of the oncolytic virus and chemotherapeutic drug, presenting a potential alternative for prostate cancer treatment and suggested that co‐administering VC and OMV in a nanoformulation could improve therapeutic outcomes while reducing chemotherapeutic drug doses.