Engineering Functional Biomaterials for Targeted and Localized Cancer Drug Delivery: A Structure-Property-Performance Design Perspective
Abstract
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…
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