Two‐Photon Mediated Cancer Therapy: A Comprehensive Review on Two‐Photon Photodynamic Therapy and Two‐Photon‐Activated Therapeutic Delivery Systems

Author:

Soleimany Amir1234,Aghmiouni Delaram Kargari1,Amirikhah Masomeh1,Shokrgozar Mohammad Ali2,Khoee Sepideh1,Sarmento Bruno34ORCID

Affiliation:

1. Polymer Laboratory School of Chemistry College of Science University of Tehran Tehran 14155–6455 Iran

2. National Cell Bank of Iran Pasteur Institute of Iran Tehran 13169‐43551 Iran

3. i3S Instituto de Investigação e Inovação em Saúde Universidade do Porto Rua Alfredo Allen 208 Porto 4200‐135 Portugal

4. IUCS‐CESPU Rua central de Gandra Gandra 4585‐116 Portugal

Abstract

AbstractTwo‐photon excitation (2PE) represents substantial advantages in biophotonics over traditional one‐photon excitation (1PE), offering enhanced spatial resolution and deeper tissue penetration capabilities. Since its introduction in the 1990s, two‐photon excited microscopy has spurred the rapid emergence of novel 2PE‐based applications, including photodynamic therapy (PDT) and the targeted release of biologically active agents. This review first elucidates the fundamental principles of 2PE before comprehensively examining the evolution of photosensitizers (PSs) for two‐photon PDT (2P‐PDT), covering both nanomaterials and small molecules, categorized based on their respective characteristics. Additionally, it explores advancements in PS development for integrating 2P‐PDT with other therapeutic modalities (e.g., photothermal therapy, chemotherapy, immunotherapy, gene therapy, etc.). Subsequent sections provide an overview of photoactivatable compounds with two‐photon absorption properties for the controlled release of various therapeutic agents (e.g., drugs, genes, and gasotransmitters), emphasizing their potential in anticancer applications. Last, a deep discussion deciphers the prospects and challenges of 2P‐mediated therapy in cancer treatment, particularly concerning their clinical translation.

Funder

Iran National Science Foundation

HORIZON EUROPE Widening Participation and Strengthening the European Research Area

Publisher

Wiley

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