From Targeted Nanoformulations to Spatial Immune Remodeling: Mechanism-Based Strategies to Enhance Anticancer Efficacy

Despite significant advances in clinical oncology, conventional cancer therapies frequently face critical hurdles, including systemic off-target toxicity, acquired multidrug resistance, and the formidable barrier of an immunosuppressive tumor microenvironment (TME). The dense structural and immunological complexity of the TME often renders malignancies “immune-cold,” severely limiting the efficacy of modern immune checkpoint blockades and cellular therapies. To overcome these limitations, mechanism-based strategies leveraging targeted nanoformulations have emerged as a transformative therapeutic approach. Advanced nanocarriers can be meticulously engineered to navigate the intricate physiological barriers of the TME, delivering therapeutic payloads with unprecedented precision. More importantly, these advanced nanomedicines are now being designed to actively orchestrate spatial immune remodeling, altering the physical and immunological landscape of the tumor to promote robust, localized anti-tumor responses.This Research Topic aims to highlight innovative, mechanism-driven strategies that enhance overall anticancer efficacy through the use of targeted nanoformulations, novel combinational therapies, and tumor-responsive biomaterials. We seek to provide a premier platform for the latest multidisciplinary discoveries detailing how advanced drug delivery systems can safely and effectively remodel the TME. A primary goal of this collection is to explore how smart nanocarriers—particularly those acting as pH-responsive, enzymatic, or redox-responsive immunomodulators—can trigger the critical conversion of immune-cold tumors into highly reactive immune-hot phenotypes. Furthermore, we aim to shed light on alternative programmed cell death mechanisms and the strategic integration of diverse therapeutic agents, including natural phytoconstituents, to bypass therapeutic resistance and establish durable immunological memory against aggressive malignancies.We welcome submissions of Original Research, Reviews, Mini-Reviews, and Perspectives that deeply investigate the mechanistic pathways and therapeutic potential of novel nanoscale platforms in modern oncology. Contributions should focus on both the underlying molecular mechanisms of action and the translational potential of these advanced therapeutic interventions.Specific themes within the scope of this Research Topic include, but are not limited to:• Mechanistic insights into enhanced anti-cancer efficacy using targeted drug delivery systems.• Design and application of actively or passively targeted nanoparticles for precision oncology.• Exploration of alternative and novel therapeutic approaches, including the use of bioactive phytoconstituents and synergistic combinational strategies.• Induction, characterization, and evaluation of alternative cell death pathways or novel anti-cancer mechanisms.• Therapeutic strategies driving the conversion of immunosuppressive “immune-cold” tumors to therapeutically responsive “immune-hot” environments.• Development and validation of stimuli-responsive (pH, enzymatic, or redox) nano-immunomodulators.• Techniques and nanocarrier formulations specifically engineered to achieve precise spatial immune remodeling within the tumor microenvironment. Topic editors: Laxman Subedi, Saurav Kumar Jha Source: https://www.frontiersin.org/research-topics/79192/from-targeted-nanoformulations-to-spatial-immune-remodeling-mechanism-based-strategies-to-enhance-anticancer-efficacy