Ashwini Shinde, Gayathri R, Nandhini Balasubramaniam, Athira Prasad, Donia Dominic, Moeto Nagai, Srabani Kar, Tuhin Subhra Santra
With the growing demand for precise and minimally invasive intracellular delivery, photoporation has emerged as a powerful non-viral strategy. This review presents a comprehensive analysis of photoporation as a versatile intracellular delivery platform, with particular emphasis on the role of micro- and nanostructured materials in enabling efficient transport across a wide range of biomolecular sizes. A key novelty of this review is its size-centric organizational framework, which systematically classifies photoporation strategies based on biomolecular cargo size, from small molecules and nucleic acids to ultralarge assemblies and bacteria, rather than conventional material- or laser-based categorizations. The review examines laser-induced mechanisms responsible for transient membrane permeabilization and highlights critical material parameters, including composition, size, shape, surface charge, and optical properties, that govern light-matter interactions and delivery efficiency. Comparative evaluation of micro- and nanostructured materials across different size regimes provides a practical framework for rational material selection and platform design. In addition, key challenges related to delivery precision, biocompatibility, scalability, and clinical translation are critically discussed alongside emerging optimization strategies. By integrating mechanistic insights with translational considerations, this review provides a structured roadmap for developing safe, efficient, and size-adaptive photoporation platforms for biological research and therapeutic applications.