Advanced photoporation technology has emerged as a powerful, non-viral strategy for the precise and minimally invasive delivery of biomolecules into cells. Researchers are increasingly turning to this platform to overcome the limitations of traditional chemical and viral methods. Consequently, this review highlights the pivotal role of micro- and nanostructured materials in facilitating efficient transport. These materials act as sensitizers that interact with laser pulses to create transient membrane pores. Furthermore, this method allows for the delivery of a wide range of cargo sizes, from small molecules to large bacterial assemblies.

Mechanisms of Biomolecular Transport

The core mechanism behind this platform involves laser-induced thermal or mechanical effects on sensitized cell membranes. Specifically, light-matter interactions at the surface of nanostructures generate vapor nanobubbles or localized heating. Therefore, these localized phenomena lead to the formation of temporary pores that allow extracellular cargo to diffuse into the cytoplasm. Moreover, the efficiency of this process depends heavily on material composition and optical properties. In addition, the shape and surface charge of the nanostructures govern how well they interact with the cell surface.

Clinical Applications of Advanced Photoporation Technology

Clinicians and researchers can now apply this technology across various therapeutic fields, particularly in oncology and gene therapy. For instance, the system enables the efficient delivery of CRISPR-Cas9 components and mRNA directly into T-cells or stem cells. Consequently, this facilitates the development of safer cell-based therapies by avoiding viral vectors. Additionally, the size-centric organizational framework allows for the rational selection of materials based on the specific cargo size. Indeed, this adaptability ensures high delivery efficiency while maintaining cellular viability across different biological contexts.

Challenges and Future Directions

Despite the significant potential, several challenges remain for clinical translation. Scaling the process for high-throughput applications and ensuring long-term biocompatibility are critical hurdles. Furthermore, researchers must optimize the platform for specific cell types that may be sensitive to laser exposure. However, emerging strategies in material design and laser modulation are addressing these issues. By integrating mechanistic insights with translational considerations, the field is moving toward a structured roadmap for clinical adoption.

Frequently Asked Questions

How does photoporation differ from electroporation?

While both create membrane pores, photoporation uses light-activated nanostructures to provide more localized and gentle permeabilization. Consequently, it often results in higher cell viability and better control over the delivery site compared to the high-voltage pulses used in electroporation.

What types of biomolecules can be delivered using this method?

Advanced photoporation technology is highly versatile. It can deliver a diverse range of cargo, including small molecule drugs, siRNA, mRNA, large plasmids, and even whole bacteria or ultra-large assemblies into targeted cells.

Disclaimer: This content is for informational and educational purposes only. It does not constitute medical advice or a professional relationship. Refer to the latest local and national guidelines for clinical practice.

References

Shinde AS et al. Advanced Photoporation: Micro-Nanostructures for Size-Specific Highly Efficient Biomolecular Delivery. Small. 2026 Feb 07. doi: 10.1002/smll.202511843. PMID: 41653467.

Xiong R et al. Laser-assisted photoporation: fundamentals, technological advances and applications. Adv Phys X. 2016;1(4):596-620.

Houthaeve G et al. The cellular response to plasma membrane disruption for nanomaterial delivery. Nano Converg. 2022;9(1):6.