Photodynamic therapy (PDT) has gained widespread attention in cancer treatment, but it still faces clinical problems such as skin phototoxicity. Activatable photosensitizers offer a promising approach to addressing this issue. However, several significant hurdles need to be overcome, including developing effective activation strategies and achieving the optimal balance between photodynamic effects and related side effects. Herein, we present a novel and general strategy for the construction of tumor-targeted activatable nanophotosensitizers (TNP1/PSs). TNP1/PSs were constructed through simple nanoprecipitation method, leveraging the strong cation-π interaction between cationic polymers and aromatic photosensitizers. We conducted a comprehensive characterization and investigation of the photoactivity, as well as the mechanisms underlying both OFF state and switched-on properties of TNP1/PSs. Additionally, we thoroughly evaluated the cytotoxicity, tumor-targeted ability, and anti-tumor efficacy of TNP1/PSs in the 4T1 cell line. TNP1/PSs exhibit a markedly fully OFF state of photoactivity, subsequent to self-assembly through cation-π interactions in aqueous media. The mechanism study reveals a multi-pathway process induced by cation-π complexes, which includes reduced absorption and radiative decay, as well as enhanced thermal decay and intermolecular charge transfer. Upon targeting tumor cells, TNP1/PSs were effectively endocytosed and predominantly traversed the lysosomes, where degradation of the cationic polymer occurs, resulting in the spontaneous switch-on of PDT activity. studies employing small animal models demonstrated that the as-synthesized nanophotosensitizer possesses remarkable anti-tumor activity while completely avoiding skin phototoxicity. This work provides a powerful platform for efficiently constructing tumor-targeted activatable nanophotosensitizers, paving the way for safe and effective photodynamic therapy in cancer treatment.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11700870 | PMC |
| http://dx.doi.org/10.7150/thno.100597 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Synthesis, characterization, and investigation of photochemical and in vitro properties of novel Zn(II) phthalocyanine.
Turk J Chem
October 2024
Department of Chemical Engineering, Faculty of Engineering and Natural Sciences, Uşak University, Uşak, Turkiye.
A new nonperipheral zinc(II) phthalocyanine bearing octa carboxylic acid ethyl ester derivative substituted triazole attached propylmercaptothiobenzylmercapto derivative was synthesized via the tetramerization reaction of phthalonitrile. The photochemical in vitro photodynamic activity of zinc(II) phthalocyanine (), such as human nonsmall cell lung carcinoma cell lines, was investigated in this study. The singlet oxygen generation property of novel zinc(II) phthalocyanine () was also examined due to the significantly high singlet oxygen quantum yield of (F = 0.
View Article and Find Full Text PDFBreaking the deep-red light absorption barrier of iridium(III)-based photosensitizers.
Dalton Trans
January 2025
Departamento de Química Inorgánica, Universidad de Murcia, Biomedical Research Institute of Murcia (IMIB-Arrixaca), E-30100 Murcia, Spain.
Activating photosensitizers with long-wavelength excitation is an important parameter for effective photodynamic therapy due to the minimal toxicity of this light, its superior tissue penetration, and excellent spatial resolution. Unfortunately, most Ir(III) complexes suffer from limited absorption within the phototherapeutic window, rendering them ineffective against deep-seated and/or large tumors, which poses a significant barrier to their clinical application. To address this issue, several efforts have been recently made to shift the absorption of Ir(III) photosensitizers to the deep-red/near-infrared region by using different strategies: functionalization with organic fluorophores, including porphyrinoid compounds, and ligand design π-extension and donor-acceptor interactions.
View Article and Find Full Text PDFModulation of Donor in Purely Organic Triplet Harvesting AIE-TADF Photosensitizer for Image-guided Photodynamic Therapy.
Small
January 2025
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati, 781039, India.
Image-guided photodynamic therapy is acknowledged as one of the most demonstrative therapeutic modalities for cancer treatment because of its high precision, non-invasiveness, and improved imaging ability. A series of purely organic photosensitizers denoted as BTMCz, BTMPTZ, and BTMPXZ, have been designed and synthesized and are found to exhibit both thermally activated delayed fluorescence and aggregation-induced emission simultaneously. Experimental and theoretical studies are combined to reveal that modulation of the donor of the photosensitizer enables distinct thermally activated delayed fluorescence via a second-order spin-orbit perturbation mechanism involving lowest singlet charge-transfer and higher-lying triplet locally excited states, respectively.
View Article and Find Full Text PDFDeep Red-Light-Mediated Nitric Oxide and Photodynamic Synergistic Antibacterial Therapy for the Treatment of Drug-Resistant Bacterial Infections.
Small
January 2025
Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, 639 Longmian Road, Jiangning, Nanjing, 210009, China.
Infections caused by persistent, drug-resistant bacteria pose significant challenges in inflammation treatment, often leading to severe morbidity and mortality. Herein, the photosensitizer rhodamine derivatives are selected as the light-trapping dye and the electron-rich substituent N-nitrosoaminophen as the nitric oxide (NO)-releasing component to develop a multifunctional (deep) red-light activatable NO photocage/photodynamic prodrug for efficient treatment of wounds and diabetic foot infections. The prodrug, RhB-NO-2 integrates antimicrobial photodynamic therapy (aPDT), NO sterilization, and NO-mediated anti-inflammatory properties within a small organic molecule and is capable of releasing NO and generating Reactive oxygen species (ROS) when exposed to (deep) red laser (660 nm).
View Article and Find Full Text PDFMorphological Features Influence the Drug Loading and Delivery Efficacy of Photoactivatable Gold Nanocarriers for Antitumor Photo/Chemotherapy.
ACS Appl Mater Interfaces
January 2025
Institute of Optical Functional Materials for Biomedical Imaging, School of Chemistry and Pharmaceutical Engineering, Shandong First Medical University & Shandong Academy of Medical Science, Taian, Shandong 271016, PR China.
Photoactivatable gold nanocarriers are transforming antitumor therapies by leveraging their distinctive physicochemical properties, enabling targeted drug delivery and enhanced therapeutic efficacy in cancer treatment. This study systematically investigates how surface topography and morphology of gold nanocarriers influence drug loading capacity, light-to-heat conversion efficiency, and overall therapeutic performance in photo/chemotherapy. We synthesized four distinct morphologies of gold nanoparticles: porous gold nanocups (PAuNCs), porous gold nanospheres (PAuNSs), solid gold nanocups (SAuNCs), and solid gold nanospheres (SAuNSs).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!