Advances in the Design of Photoactivatable Metallodrugs: Excited State Metallomics

Angewandte Chemie, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

Abstract Photoactivatable metal complexes offer the prospect of novel drugs with low side effects and new mechanisms action to combat resistance current therapy. We highlight recent progress in design platinum, ruthenium, iridium, gold other transition complexes, especially for applications as anticancer anti‐infective agents. In particular, understanding excited state chemistry related identification bioactive species (excited metallomics/pharmacophores) is important. metallodrugs are classified here photocatalysts, photorelease agents ligand‐activated Their activation wavelengths, cellular action, experimental theoretical metallomics states photoproducts discussed explore strategies investigation photoactivatable metallodrugs. These have potential clinical Photodynamic Therapy (PDT), Photoactivated Chemotherapy (PACT) Photothermal (PTT).

Language: Английский

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Ruthenium(II) Polypyridyl Complexes Containing COUBPY Ligands as Potent Photosensitizers for the Efficient Phototherapy of Hypoxic Tumors

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: 147(9), P. 7360 - 7376

Published: Feb. 15, 2025

Hypoxia, a hallmark of many solid tumors, is linked to increased cancer aggressiveness, metastasis, and resistance conventional therapies, leading poor patient outcomes. This challenges the efficiency photodynamic therapy (PDT), which relies on generation cytotoxic reactive oxygen species (ROS) through irradiation photosensitizer (PS), process partially dependent levels. In this work, we introduce novel family potent PSs based ruthenium(II) polypyridyl complexes with 2,2′-bipyridyl ligands derived from COUPY coumarins, termed COUBPYs. Ru-COUBPY exhibit outstanding in vitro cytotoxicity against CT-26 cells when irradiated light within phototherapeutic window, achieving nanomolar potency both normoxic hypoxic conditions while remaining nontoxic dark, impressive phototoxic indices (>30,000). Their ability generate Type I II ROS underpins their exceptional PDT efficiency. The lead compound study, SCV49, shows favorable vivo pharmacokinetic profile, excellent toxicological tolerability, tumor growth inhibition mice bearing subcutaneous tumors at doses as low 3 mg/kg upon deep-red (660 nm). These results allow us propose SCV49 strong candidate for further preclinical development, particularly treating large tumors.

Language: Английский

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Immunogenic Cell Death Induction and Oxygenation by Multifunctional Hollow Silica/Copper-Doped Carbon Dots

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: 16(15), P. 18534 - 18550

Published: April 4, 2024

The metastasis and recurrence of cancer are related to immunosuppression hypoxia in the tumor microenvironment. Activating immune activity improving hypoxic environment face essential challenges. This paper reports on a multifunctional nanomaterial, HSCCMBC, that induces immunogenic cell death through powerful photodynamic therapy/chemodynamic therapy synergistic antitumor effects. microenvironment changed from immunosuppressive type type, activated system, decomposed hydrogen peroxide generate oxygen based Fenton-like reaction, effectively increased level intracellular O2 with assistance 3-bromopyruvate, respiratory inhibitor. structure composition HSCCMBC were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, diffraction, infrared etc. Oxygen probe RDPP was used investigate inside outside cell, hydroxyl radical tetramethylbenzidine reaction ability. immunofluorescence method investigated expression various markers hypoxia-inducing factors vitro vivo after treatment. In experiments indicate is an excellent agent expected be candidate drug for immunotherapy.

Language: Английский

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A Supramolecular, Triple Negative Breast Cancer‐Targeting Avidin‐Photosensitizer

Macromolecular Bioscience, Journal Year: 2025, Volume and Issue: unknown

Published: March 25, 2025

The potential of photodynamic therapy (PDT) in combination with chemotherapy to improve treatment outcomes for triple-negative breast cancer (TNBC), which no targeted is available, the subject considerable investigation. In PDT, photosensitizers (PSs) are frequently administered directly but do not selectively target cells. To address delivery a PS TNBC and enhance cellular uptake, Ru-NH2-modified avidin bioconjugate (RuAvi) via Tyr-specific modification using Mannich reaction prepared. RuAvi further assembled cinnamoyl peptide-F(D)LF(D)LFK-NH2 (FK), binds formyl peptide receptor 1, overexpressed TNBC. Notably, modified Avi still possesses ability efficiently bind biotin assembly up four copies FK peptides. resultant FK4-RuAvi exhibited an IC50 value 0.36 ± 0.08 µM, ≈3.5-fold lower than that (1.25 0.09 µM), upon irradiation MDA-MB-231 also shows efficient uptake tumor spheroids significant toxicity after compared control RuAvi. presented strategy has efficacy PDT meet high demand therapies treat TNBC, such as adjuvant surgery.

Language: Английский

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A Lanthanide Nanoparticle–Aggregation-Induced Emission Photosensitizer Complex System Drives Coupled Triplet Energy Transfer for Enhanced Radio-Photodynamic Therapy

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Cerenkov light (CL), utilized as an internal excitation source for photodynamic therapy (PDT), addresses the limitations of laser penetration and has substantial potential seamlessly integrating clinical radiotheranostics with phototheranostics. Nevertheless, effectiveness CL-mediated PDT is significantly hindered by challenges, such low intensity CL inadequate energy transfer between donor photosensitizers (PSs). In this study, a novel approach introduced enhanced radionuclide-activated radio-photodynamic utilizing hybrid nanoparticle system composed lanthanide nanoparticles aggregation-induced emission photosensitizer (AIE PS), designated LnNP–TQ NPs. This enables to optimize decay radionuclides, effectively sensitizing AIE PS through triplet (TET)-mediated processes efficiency approaching 100%. When activated radionuclide 18F positron tomography imaging, NPs substantially inhibited tumor growth via effective singlet oxygen (1O2) generation. strategy, which optimally harnesses achieves efficient transfer, offers promising pathway enhancing radiotherapy–phototherapy efficacy in treatment.

Language: Английский

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