Work

A Microneedle Patch Delivers Mitochondria‐ and Lysosomes‐ Dual Targeting Prodrug‐Like Photosensitizers with Regulated Photoactivity for Precise Photodynamic Therapy

Year: 2025

Type: article

Abstract: Antitumor photodynamic therapy (PDT) faces huge challenges as selectivity and phototoxic damage, requiring delivery photosensitizers (PSs) to specifically accumulate in tumors even in organelle, and avoid the phototoxic damage during delivery. Herein, a microneedle patch (AIE‐mito‐TPP@MN) containing mitochondria‐ and lysosomes‐ dual targeting prodrug‐like PSs (AIE‐mito‐TPP/AlPcSNa4) that is self‐assembled by mitochondria‐targeted aggregation‐induced‐emission molecule (AIE‐mito‐TPP) and lysosome‐targeted aluminum phthalocyanine tetrasulfonate (AlPcSNa4), is developed to achieve cancer‐cell‐organelle‐specific targeting delivery for precise PDT with high selectivity and low phototoxic damage. AIE‐mito‐TPP/AlPcSNa4 displays prodrug‐like activity via the regulated photoactivity to reduce the phototoxic damage caused by the “always on” PSs. Meanwhile, AIE‐mito‐TPP/AlPcSNa4@MN can insert into the epidermis to achieve rapid AIE‐mito‐TPP/AlPcSNa4 delivery in tumor lesion, and enhance selective accumulation in tumor cells. The higher lysosomal acidity in tumor cells facilitates AIE‐mito‐TPP/AlPcSNa4 disassembly and promotes targeting. Under light irradiation, AIE‐mito‐TPP/AlPcSNa4@MN impairs mitochondrial and lysosomal function to induce deeper tumor cells apoptosis at a low dose (≈6 µg), presenting greater therapeutic efficacy than AIE‐mito‐TPP@MN, AlPcSNa4@MN, or intravenous injection. Moreover, AIE‐mito‐TPP/AlPcSNa4@MN presents good biocompatibility as lower accumulation and targeting in normal cells, as well as the regulated photoactivity of prodrug‐like PSs. Therefore, the dual organelle‐targeting microneedle possesses great potential for precise PDT with high selectivity.

Source: Advanced Healthcare Materials

DOI: 10.1002/adhm.202403954

Authors: Zheng Liu, Zhimin Tang, Ying Yin, Miaojian Wan, Jiezhao Zhan, Li Ren

Institutions: South China University of Technology, Third Affiliated Hospital of Sun Yat-sen University

Language: English

Topic: Photodynamic Therapy Research Studies

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: National Natural Science Foundation of China, Basic and Applied Basic Research Foundation of Guangdong Province