Harnessing exosomes and hybrid nanoplatforms for pancreatic cancer therapy: Navigating challenges from bench to bedside

Abstract

Background Pancreatic cancer (PC) is a devastating malignancy characterized by late diagnosis and profound drug resistance. This review aims to systematically evaluate the therapeutic and diagnostic potential of exosomes and advanced exosome-nanoparticle hybrid platforms in PC. Methods A systematic literature search was conducted across PubMed, Scopus, and Web of Science databases for studies published between 2015 and 2026, strictly following PRISMA guidelines. Eligibility criteria explicitly focused on studies evaluating engineered exosome-nanoparticle hybrid platforms for targeted drug delivery in pancreatic cancer models. Methodological quality and risk of bias for the included preclinical in vivo studies were critically evaluated by assessing core experimental parameters, including sequence generation (randomization), blinding, and selective outcome reporting. Due to the structural heterogeneity of the platforms, data were synthesized qualitatively. Results From 3008 initial records, 161 references were utilized for the comprehensive narrative, while 4 high-impact studies focusing strictly on hybrid platforms were systematically synthesized. Results demonstrate that engineered hybrid systems achieve superior tumor penetration, with specific platforms reaching a 90.3% tumor inhibition rate in vivo. Early-phase clinical trials (e.g., NCT03608631) confirm the feasibility of engineered exosomes in delivering gene-silencing cargo across the stromal barrier with manageable safety. Discussion /Conclusion: Hybrid platforms offer a transformative avenue for PC therapy. While the certainty of preclinical evidence regarding tumor penetration is high, the overall confidence in widespread clinical translation remains moderate due to challenges in scalable, cGMP-compliant production and standardization.