Engineering Functional Biomaterials for Targeted and Localized Cancer Drug Delivery: A Structure-Property-Performance...

Background/Objectives: Cancer therapy remains limited by poor tumor selectivity, systemic toxicity, biological barriers to drug transport, rapid clearance, treatment resistance, and postoperative recurrence. Functional biomaterials offer engineered systems to address these limitations through targeted, localized, controlled, and stimuli-responsive drug delivery. However, existing reviews commonly classify these systems according to carrier type, therapeutic agent, or cancer application, with less emphasis on how biomaterial structure and physicochemical properties determine therapeutic performance. This review addresses this gap using a structure-property-performance (SPP) framework to rationally engineer functional biomaterials for targeted, localized cancer drug delivery. Methods: The review critically examines particle size and morphology, surface chemistry and charge, targeting functionalization, stimulus responsiveness, porosity and internal architecture, mechanical stability, and degradation, and relates these design parameters to drug loading and release, systemic transport, tumor accumulation and penetration, cellular uptake, and local retention. Selected mechanistic relationships, including equations for particle diffusion, membrane wrapping, receptor-mediated endocytosis, particle aspect ratio, porous-matrix transport, implant-associated tissue diffusion, and porosity-dependent stiffness, are also discussed to support quantitative interpretation of SPP relationships. The review further evaluates these relationships across cancer-specific biomaterial applications. Results: The reviewed evidence shows that biomaterial properties are strongly interdependent and often involve competing requirements, so optimizing one property can improve one aspect of therapeutic performance while limiting another. Cancer-specific applications in breast, brain, colorectal, pancreatic, melanoma, ovarian, bladder, and bone cancers further demonstrate that effective biomaterial design must be matched to disease-specific biological and anatomical barriers. Conclusions: The SPP framework provides a design approach for moving functional biomaterials from empirical formulation toward integrated, application-specific design. Future development is expected to increasingly incorporate AI-guided and personalized design, image-guided delivery, multi-responsive functionality, and integration of cancer therapy with tissue regeneration to advance more precise and clinically translatable cancer treatments.