Enzyme-Directed and Organelle-Specific Sphere-to-Fiber Nanotransformation Enhances Photodynamic Therapy in Cancer Cells.

Autor: Gan S; Department of Chemistry and COSDAF (Centre of Super-Diamond and Advanced Films) City University of Hong Kong, Hong Kong, 999077, China.; Key Laboratory of Biochip Technology, Biotech and Health Centre, Shenzhen Research Institute of City University of Hong Kong, Shenzhen, 518057, China., Yang L; College of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan, 410083, China., Heng Y; Department of Chemistry and COSDAF (Centre of Super-Diamond and Advanced Films) City University of Hong Kong, Hong Kong, 999077, China.; Key Laboratory of Biochip Technology, Biotech and Health Centre, Shenzhen Research Institute of City University of Hong Kong, Shenzhen, 518057, China., Chen Q; Department of Chemistry and COSDAF (Centre of Super-Diamond and Advanced Films) City University of Hong Kong, Hong Kong, 999077, China.; Key Laboratory of Biochip Technology, Biotech and Health Centre, Shenzhen Research Institute of City University of Hong Kong, Shenzhen, 518057, China., Wang D; Department of Chemistry and COSDAF (Centre of Super-Diamond and Advanced Films) City University of Hong Kong, Hong Kong, 999077, China.; Key Laboratory of Biochip Technology, Biotech and Health Centre, Shenzhen Research Institute of City University of Hong Kong, Shenzhen, 518057, China.; Sichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, China., Zhang J; Department of Chemistry and COSDAF (Centre of Super-Diamond and Advanced Films) City University of Hong Kong, Hong Kong, 999077, China.; Key Laboratory of Biochip Technology, Biotech and Health Centre, Shenzhen Research Institute of City University of Hong Kong, Shenzhen, 518057, China., Wei W; Department of Chemistry and COSDAF (Centre of Super-Diamond and Advanced Films) City University of Hong Kong, Hong Kong, 999077, China., Liu Z; Department of Chemistry and COSDAF (Centre of Super-Diamond and Advanced Films) City University of Hong Kong, Hong Kong, 999077, China.; Key Laboratory of Biochip Technology, Biotech and Health Centre, Shenzhen Research Institute of City University of Hong Kong, Shenzhen, 518057, China., Njoku DI; Department of Applied Science, Hong Kong Metropolitan University, Ho Man Tin, Kowloon, Hong Kong, 999077, China., Chen JL; Department of Applied Science, Hong Kong Metropolitan University, Ho Man Tin, Kowloon, Hong Kong, 999077, China., Hu Y; State Key Laboratory of Complex, Severe, and Rare Diseases, Biomedical Engineering Facility of National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Beijing, 100730, China., Sun H; Department of Chemistry and COSDAF (Centre of Super-Diamond and Advanced Films) City University of Hong Kong, Hong Kong, 999077, China.; Key Laboratory of Biochip Technology, Biotech and Health Centre, Shenzhen Research Institute of City University of Hong Kong, Shenzhen, 518057, China.
Jazyk: angličtina
Zdroj: Small methods [Small Methods] 2024 Nov; Vol. 8 (11), pp. e2301551. Date of Electronic Publication: 2024 Feb 19.
DOI: 10.1002/smtd.202301551
Abstrakt: Employing responsive nanoplatforms as carriers for photosensitizers represents an effective strategy to overcome the challenges associated with photodynamic therapy (PDT), including poor solubility, low bioavailability, and high systemic toxicity. Drawing inspiration from the morphology transitions in biological systems, a general approach to enhance PDT that utilizes enzyme-responsive nanoplatforms is developed. The transformation of phosphopeptide/photosensitizer co-assembled nanoparticles is first demonstrated into nanofibers when exposed to cytoplasmic enzyme alkaline phosphatase. This transition is primarily driven by alkaline phosphatase-induced changes of the nanoparticles in the hydrophilic and hydrophobic balance, and intermolecular electrostatic interactions within the nanoparticles. The resulting nanofibers exhibit improved ability of generating reactive oxygen species (ROS), intracellular accumulation, and retention in cancer cells. Furthermore, the enzyme-responsive nanoplatform is expanded to selectively target mitochondria by mitochondria-specific enzyme sirtuin 5 (SIRT5). Under the catalysis of SIRT5, the succinylated peptide/photosensitizer co-assembled nanoparticles can be transformed into nanofibers specifically within the mitochondria. The resulting nanofibers exhibit excellent capability of modulating mitochondrial activity, enhanced ROS formation, and significant anticancer efficacy via PDT. Consequently, the enzyme-instructed in situ fibrillar transformation of peptide/photosensitizers co-assembled nanoparticles provides an efficient pathway to address the challenges associated with photosensitizers. It is envisaged that this approach will further expand the toolbox for enzyme-responsive biomaterials for cancer therapy.
(© 2024 The Authors. Small Methods published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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