Lysosome-specific chemical platforms for precision oncology: from structural design to biological applications

Abstract

The complex mechanisms of tumorigenesis and the inherent limitations of conventional therapies have severely restricted the clinical efficacy of tumor treatment. Owing to their pivotal roles in macromolecular degradation, energy metabolism, autophagy, and signal transduction, lysosomes are increasingly recognized as important targets for precision oncology. In this review, we summarize advances made over the past five years in the development of lysosome-specific chemical platforms for tumor therapy, covering molecular, material, and biomimetic platforms. Through comprehensive assessment of their structural designs, mechanisms of action, and representative applications, this review highlights the advantages and challenges of these platforms in drug delivery, photodynamic/photothermal therapy, immunotherapy, biomimetic strategies, and targeting imaging. Moreover, the unique acidic microenvironment and membrane permeability of lysosomes provide favorable conditions for lysosomal escape, offering another potential and critical mechanism to target as a new tumor treatment strategy. In addition to lysosomal escape, lysosome-specific platforms can target membrane permeability and remodeling of the immune microenvironment in enhancing therapeutic efficacy and overcoming drug resistance. Finally, we highlight the future directions and clinical translation prospects of lysosome-specific self-assembling peptide platforms, coacervates, chimeras, and near-infrared small-molecule probes, emphasizing the critical role of interdisciplinary integration in advancing precision tumor theranostics.