Background: Hypoxia-activated prodrugs present new opportunities for safe and effective tumor drug resistance therapy due to their high selectivity for hypoxic cells. However, the uneven distribution of oxygen in solid tumor and insufficient hypoxia in the tumor microenvironment greatly limit its therapeutic efficacy.
Results: In this paper, a novel AQ4N-Mn(II)@PDA coordination nanoplatform was designed and functionalized with GMBP1 to target drug-resistant tumor cells. Its excellent photothermal conversion efficiency could achieve local high-temperature photothermal therapy in tumors, which could not only effectively exacerbate tumor hypoxia and thus improve the efficacy of hypoxia-activated chemotherapy of AQ4N but also significantly accelerate Mn-mediated Fenton-like activity to enhance chemodynamic therapy. Moreover, real-time monitoring of blood oxygen saturation through photoacoustic imaging could reflect the hypoxic status of tumors during treatment. Furthermore, synergistic treatment effectively inhibited tumor growth and improved the survival rate of mice bearing orthotopic drug-resistant tumors.
Conclusions: This study not only provided a new idea for PTT combined with hypoxia-activated chemotherapy and CDT for drug-resistant tumors but also explored a vital theory for real-time monitoring of hypoxia during treatment.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11200845 | PMC |
| http://dx.doi.org/10.1186/s12951-024-02653-8 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Hypoxia-activated dissociation of heteroleptic cobalt(III) complexes with functionalized 2,2'-bipyridines and a model anticancer drug esculetin.
Dalton Trans
January 2025
A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119334, Vavilova Str., 28, bld. 1, Moscow, Russia.
A low oxygen level in solid tumors is behind the modern concept of selective chemotherapy by hypoxia-activated prodrugs, such as heteroleptic complexes of transition metals (cobalt(III), iron(III) or platinum(IV)) with bi- or tetradentate ligands and an anticancer drug molecule as a co-ligand. A series of new cobalt(III) complexes [Co(LR)(esc)]ClO with esculetin (6,7-dihydroxycoumarin) and 2,2'-bipyridines (2,2'-bipy) functionalized by different substituents R were probed in the hypoxia-activated delivery of this model anticancer drug. Their combined study by cyclic voltammetry and NMR spectroscopy allowed identifying linear correlations of the electrochemical reduction potentials and the rate of the hypoxia-activated dissociation of [Co(LR)(esc)]ClO with the Hammett constants of the substituents in 2,2'-bipy ligands.
View Article and Find Full Text PDFMannose functionalized small molecule nanodrug self-assembled from amphiphilic prodrug connected by disulfide bonds for synergistic cancer chemotherapy and photodynamic/photothermal therapy.
Int J Pharm
January 2025
School of Traditional Chinese Pharmacy, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, PR China. Electronic address:
Compared to conventional nanocarrier-based drug delivery technology, small-molecule-assembled nanomaterials provide various advantages, including higher drug loading efficiency, lower excipient-related toxicity, and a simpler formulation process. Our research constructed a mannonse-modified small-molecule-assembled nanodrug for synergistic photodynamic/chemotherapy against A549 cancer cells. The hydrophobic hypoxic-activated agent tirapazamine (TPZ) and a hydrophilic fluorescence probe Cyanine 3 (Cy3) constitute this amphiphilic prodrug via a glutathione (GSH)-responsive linkage, which could self-assemble into stable nanoparticles (NPs) and encapsulate a newly synthesized photosensitizer (SeBDP).
View Article and Find Full Text PDFA Hypoxia-Activated BODIPY-Azo Anticancer Prodrug for Bimodal Chemo-Photodynamic Therapy.
J Med Chem
January 2025
Department of Medicinal Chemistry, Hebei Medical University, Shijiazhuang 050017, China.
For cancer treatment, collaborative strategies have been the mainstream for overcoming the restrictions resulting from monotherapy. Combining chemotherapy with photodynamic therapy (PDT) has been shown to increase the antitumor effect and reduce side impacts. This study reports a hypoxia-activated prodrug BOD-Azo-single with a PDT agent and aniline mustard connected by the azo bond.
View Article and Find Full Text PDFBiocompatible nanoparticles self-assembled by PEGylated polyphosphoesters for combination of photodynamic therapy and hypoxia-activated chemotherapy against breast cancer.
Front Pharmacol
December 2024
Department of Radiology, Tianjin Key Laboratory of Functional Imaging and Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin, China.
Introduction: Although photodynamic therapy (PDT) shows considerable potential for cancer treatment due to its precise spatial control and reduced toxicity, effectively eliminating residual cells under hypoxic conditions remains challenging because of the resistance conferred by these cells.
Methods: Herein, we synthesize an amphiphilic PEGylated polyphosphoester and present a nanocarrier (NP) specifically designed for the codelivery of hydrophobic photosensitizer (chlorin e6, Ce6) and hypoxia-activated prodrugs (tirapazamine, TPZ). We investigate the antitumor effect of NP on both cellular and animal level.
Transferrin Protein Corona-Targeted Codelivery of Tirapazamine and IR820 Facilitates Efficient PDT-Induced Hypoxic Chemotherapy on 4T1 Breast Cancer.
ACS Appl Mater Interfaces
January 2025
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Protein corona (PC) formation confers novel biological properties to the original nanomaterial, impeding its uptake and targeting efficacy in cells and tissues. Although many studies discussing PC formation have focused on inert proteins that may inhibit the function of nanomaterials, some functional plasma proteins with intrinsic targeting capabilities can also be adsorbed to the surface of nanomaterials, with active ligand properties to improve the targeting ability. In this approach, nanomaterials are surface-engineered to promote the adsorption of specific functional plasma proteins that are directly targeted to transport nanomaterials to the target site.
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!