Extracellular vesicles as biomimetic platforms for photo-assisted cancer therapy: evolution from synthetic nanocarriers to engineered therapeutic systems.

Photo-assisted therapies have emerged as promising strategies for cancer treatment by combining localized tumor ablation with the induction of systemic antitumor immune responses. Despite encouraging preclinical and clinical advances, their therapeutic efficacy remains limited by the unfavorable pharmacokinetics, poor tumor selectivity, restricted tissue penetration, and off-target toxicity of conventional photosensitizer formulations. Although synthetic nanocarriers have substantially improved photosensitizer delivery, their limited biological functionality has driven the development of biomimetic drug delivery systems capable of actively interacting with the tumor microenvironment. Among these, extracellular vesicles have rapidly emerged as highly attractive therapeutic platforms owing to their intrinsic biocompatibility, prolonged circulation, natural tissue tropism, ability to cross biological barriers, and unique role in intercellular communication. In this review, we examine the evolution of extracellular vesicle-based photo-assisted therapeutic platforms from passive drug carriers to engineered biomimetic systems integrating multiple biological and therapeutic functions. We first discuss the transition from synthetic nanocarriers to extracellular vesicles and summarize the biological properties that distinguish these natural nanocarriers from conventional delivery systems. We then analyze current engineering strategies for optimizing therapeutic cargo loading and programming the extracellular vesicle biological interface through chemical, genetic, and biomimetic approaches that enhance tumor targeting, intracellular trafficking, and communication with the tumor microenvironment. Building upon these advances, we propose a functional framework describing the progressive evolution of extracellular vesicle-based photo-assisted platforms from targeted delivery systems to multifunctional nanotherapeutics integrating immune modulation, ferroptosis induction, metabolic reprogramming, hypoxia alleviation, image-guided therapy, and theranostic and image-guided capabilities. Finally, we discuss the major biological, technological, manufacturing, and regulatory barriers that currently limit clinical translation and highlight emerging opportunities for developing engineered extracellular vesicles capable of sensing, communicating with, and dynamically remodeling the tumor ecosystem. Together, this review provides a critical overview of current developments in EV-based photo-assisted cancer therapy, distinguishing experimentally demonstrated engineering strategies from emerging concepts whose translational feasibility remains to be established. Despite these advances, EV-based photo-assisted therapeutic platforms remain at the preclinical stage, with no clinical trials yet evaluating their therapeutic use in humans.