Mitochondria‐Targeted Small‐Molecule Fluorophores for Dual Modal Cancer Phototherapy

Abstract

Mitochondria are recognized as the ideal target for cancer treatment because they play a central role in oxidative metabolism and apoptosis. In this work, a mitochondria‐targeted near‐infrared (NIR) photosensitizer (PS) for synchronous cancer photodynamic therapy (PDT) and photothermal therapy (PTT) is synthesized. This multifunctional small‐molecule PS is developed from a variety of synthesized heptamethine cyanine dyes, which are modified with various N‐alkyl side chains on the lipophilic cationic heptamethine core. It is demonstrated to preferentially accumulate in cancer cells by organic‐anion transporting polypeptide mediated active transport and retain in mitochondria by its lipophilic cationic property. As mitochondria are susceptible to hyperthermia and excessive reactive oxygen species, this new PS integrating PTT and PDT treatment exhibits highly efficient phototherapy in multiple cancer cells and animal xenograft models. Furthermore, this targeted PS with NIR imaging property also enables tumors and their margins clearly visualized, providing the potential for precisely imaging‐guided phototherapy and treatment monitoring. This is the first report that a small‐molecule PS integrates both cancer PTT and PDT treatment by targeting mitochondria, significantly increasing the photosensitization. This work may also present a practicable strategy to develop small‐molecule‐based cancer theranostic agents for simultaneous cancer targeting, imaging, and therapy.

Boron Dipyrromethene Nano‐Photosensitizers for Anticancer Phototherapies

“…As a burgeoning cancer tool, phototherapy offers specific spatiotemporal selectivity and minimal invasion into healthy tissues . Phototherapy generally involves the activation of photosensitizers (PSs) under light irradiation to induce cancer cell phototoxicity by generating reactive oxygen species (ROS) (photodynamic therapy, PDT) or heating via nonradiative relaxation pathways (photothermal therapy, PTT) …”

Mitochondria‐Targeted Polydopamine Nanocomposite with AIE Photosensitizer for Image‐Guided Photodynamic and Photothermal Tumor Ablation

“…The death of cancer cells has a big deal with the function of mitochondria. Recently, many workers focus on exploring the treatment on the basis of targeting and delivering drugs into mitochondria . Promoting mitochondrial ROS production to induce cancer cell death can improve chemotherapy effect .…”

Mitochondria‐Targeted Water‐Soluble Organic Nanoparticles of Chlorin Derivatives for Biocompatible Photodynamic Therapy

“…[39][40] Mitochondria-targeting has attracted much attention for inducing mitochondriamediated apoptosis based on enhanced ROS generation, which can destroy the mitochondrial membrane, [41][42] resulting in effective therapeutic activity. [25,[43][44][45][46][47][48][49] Besides triphenylphosphonium and other lipophilic cations (ammonium), there are very few mitochondria-targeting agents. To the best of our knowledge, this is the first example of mitochondria-targeting in cells using WSONs of chlorin derivatives in PDT.…”