Abstract
Over the years, cancer has continued to be a leading global health threat, prompting researchers to explore advanced therapies that go beyond traditional treatments like chemotherapy and radiotherapy. Among these advanced therapies, gene therapy and immunotherapy have shown significant promise in treating cancer by either altering genetic makeup or stimulating the immune system. However, their clinical applications face significant obstacles such as poor drug delivery, rapid degradation, and immune system clearance. Hybrid nanocarriers have emerged as a transformative development in modern precision oncology, enabling the co-delivery of gene therapy and immunotherapy agents in a highly targeted manner to address the persistent limitations of traditional cancer treatments. This review focuses on hybrid nanocarrier systems specifically engineered for co-delivery applications and critically evaluates when and how these multifunctional platforms outperform conventional single-modality or non-hybrid formulations. We compare key hybrid architectures in terms of payload compatibility, pharmacokinetics, immune modulation, and translational readiness, and examine the influence of tumor microenvironmental characteristics on their therapeutic performance. Particular emphasis is placed on stimuli-responsive designs, biomimetic surface engineering, and artificial intelligence-assisted optimization as emerging strategies to enhance co-delivery efficacy. By synthesizing current evidence and identifying key scientific and manufacturing gaps, this review aims to provide a practical foundation for advancing hybrid nanocarriers from laboratory development to clinically meaningful, personalized cancer therapies.