Radiation-Activated Nanoplatforms for Precision Oncology: Emerging Design Strategies, Biological Mechanisms, and Clinical Translation

Abstract

Radiation-activated nanoplatforms are emerging as a promising weapon to the biological and physical barriers of conventional radiotherapy by integrating radiation-induced therapeutic processes with nanoscale material engineering. This review critically assesses the radiation-activated nanoplatforms in relation to the correlation between the structure of the nanomaterials, radiation-nanomaterial interactions, tumor biology, tumor therapeutic mechanisms, and clinical translation of the nanomaterials in precision oncology. High-Z nanoparticles, nanocarriers that respond to radiation, nanomaterials that generate ROS, nanozymes, oxygen-modulating systems, hypoxia-responsive systems, and multifunctional core-shell nanoparticles. Particular attention to the secondary generation of electrons, amplification of ROS, the regulation of oxygen, the controlled release of drugs, the destruction of DNA, the dysfunction of mitochondria, ferroptosis, and immune-cell death. Their combination with chemotherapy, immunotherapy, photothermal/photodynamic therapy, and theranostic imaging are also discussed. An emerging nanostructure-radiation-biology-clinical outcome framework that serves to bridge nanoscale radiation physics to molecular damage, regulated cell death, controlled remodeling of the tumor microenvironment, and antitumor immunity is one of the novelty features. A new paradigm of precision translation that incorporates molecular profiling, nanoparticle biodistribution, image-guided nanodosimetry, personalized radiation dosing and AI-driven treatment adaptation is also encouraged by the review. Challenges like the heterogeneous tumor penetration, off-target accumulation, long-term toxicity, variability in manufacturing process, complexity in regulations as well as nanoscale dosimetry are critically assessed. Opportunities for the future include self-regulating therapeutic systems, biodegradable nanomaterials, sustainable synthesis, and AI-guided design. Overall, one can imagine smarter, intelligent, and clinically fabricable nanoplatforms that would transform the approach to radiation application to elicit a therapeutic response in personalized cancer therapy.