A Meta-analysis on the Effectiveness of Extracellular Vesicles as Nanosystems for Targeted Delivery of Anticancer Drugs.

While the efficacy of anticancer drugs is hampered by low bioavailability and systemic toxicity, the uncertainty remains whether encapsulation of these drugs into natural nanovesicles such as extracellular vesicles (EVs) could improve controlled drug release and efficacy for targeted tumor therapy. Thus, we performed a meta-analysis for studies reporting the efficacy of EVs as nanosystems to deliver drugs and nucleic acid, protein, and virus (NPV) to tumors using the random-effects model. The electronic search of articles was conducted through Cochrane, PubMed, Scopus, Science Direct, and Clinical Trials Registry from inception up till September 2022. The pooled summary estimate and 95% confidence interval of tumor growth inhibition, survival, and tumor targeting were obtained to assess the efficacy. The search yielded a total of 119 studies that met the inclusion criteria having only 1 clinical study. It was observed that the drug-loaded EV was more efficacious than the free drug in reducing tumor volume and weight with the standardized mean difference (SMD) of -1.99 (95% CI: -2.36, -1.63; p < 0.00001) and -2.12 (95% CI: -2.48, -1.77; p < 0.00001). Similarly, the mean estimate of tumor volume and weight for NPV were the following: SMD: -2.30, 95% CI: -3.03, -1.58; p < 0.00001 and SMD: -2.05, 95% CI: -2.79, -1.30; p < 0.00001. Treatment of tumors with EV-loaded anticancer agents also prolonged survival (HR: 0.15, 95% CI: 0.10, 0.22, p < 0.00001). Furthermore, EVs significantly delivered drugs to tumors as revealed by the higher concentration at the tumor site (SMD: -2.73, 95% CI: -3.77, -1.69; p < 0.00001). This meta-analysis revealed that EV-loaded drugs and NPV performed significantly better in tumor growth inhibition with improved survival than the free anticancer agents, suggesting EVs as safe nanoplatforms for targeted tumor therapy.