TRAIL of Hope: Bioactive Dietary Component-Driven Carrier-Free Nanoplatforms for Synergistically Enhanced Tumor Multimodal Therapy.

Considering the inherent drawbacks of conventional anticancer drugs, such as suboptimal efficacy and undesirable toxicity, functional dietary components have been increasingly focused on achieving optimal therapeutic performance and minimizing side effects. A combination of nanoscience and drug delivery gave birth to nanomedicine, the field exploring the potential of the distinct physicochemical and biological behavior of nanostructures to enhance treatment and decrease toxicity. Nevertheless, the tumor microenvironment (TME) is exceptionally complex, and until recently, no targeted nano-delivery system has demonstrated robust therapeutic efficacy in cancer. Carrier-free nanomedicines based on functional dietary components present a promising platform for multimodal tumor therapy. This comprehensive review explored delivery strategies for emerging functional dietary component-based intelligent nanoplatforms, covering publications from 2024 to 2025. Functional dietary-component-based, carrier-free nanoplatforms represent an emerging therapeutic strategy that has been extensively investigated and may revolutionize cancer therapy by using functional dietary components as building blocks for self-assembled nanostructures, thereby avoiding extraneous materials and enabling higher drug loading, optimized drug ratios, simplified techniques, and higher biosafety. Numerous dietary components, including capsaicin, chlorogenic acid, curcumin, epigallocatechin gallate, erianin, galangin, gossypol, mangiferin, quercetin, and ursolic acid, have been extensively studied in recent years as candidates for anticancer therapy. Simultaneously, as smart nanoplatforms develop towards non-invasive, minimally invasive, and intelligent therapy strategies, various carrier-free nanomedicines have emerged to facilitate multimodal cancer therapies. Strategies targeting a combination of functional dietary components and chemotherapy, chemodynamic therapy, immunotherapy, photodynamic therapy, photothermal therapy, and sonodynamic therapy are promising for clinical cancer therapy. This study covers recent advances in carrier-free nanoplatforms and provides a systematic evaluation of this exciting field, highlighting the transformative role of functional dietary components in nanomedicine. This article explores the multidimensional challenges faced by smart nanoplatforms and offers insightful perspectives for their clinical translation.