Acceptor engineering of metallacycles with high phototoxicity indices for safe and effective photodynamic therapy DOI Creative Commons

Chonglu Li,

Le Tu,

Jingfang Yang

et al.

Chemical Science, Journal Year: 2023, Volume and Issue: 14(11), P. 2901 - 2909

Published: Jan. 1, 2023

Although metallacycle-based photosensitizers have attracted increasing attention in biomedicine, their clinical application has been hindered by inherent dark toxicity and unsatisfactory phototherapeutic efficiency. Herein, we employ a π-expansion strategy for ruthenium acceptors to develop series of Ru(ii) metallacycles (Ru1-Ru4), while simultaneously reducing enhancing phototoxicity, thus obtaining high phototoxicity index (PI). These enable deep-tissue (∼7 mm) fluorescence imaging reactive oxygen species (ROS) production exhibit remarkable anti-tumor activity even under hypoxic conditions. Notably, Ru4 the lowest toxicity, highest ROS generation ability an optimal PI (∼146). Theoretical calculations verify that exhibits largest steric bulk singlet-triplet energy gap (ΔEST, 0.62 eV). In vivo studies confirm allows effective safe phototherapy against A549 tumors. This work is expected open new avenue design high-performance metal-based potential applications.

Language: Английский

Photodynamic and Photothermal Therapies: Synergy Opportunities for Nanomedicine DOI Creative Commons
Marta Overchuk, Robert Weersink, Brian C. Wilson

et al.

ACS Nano, Journal Year: 2023, Volume and Issue: 17(9), P. 7979 - 8003

Published: April 27, 2023

Tumoricidal photodynamic (PDT) and photothermal (PTT) therapies harness light to eliminate cancer cells with spatiotemporal precision by either generating reactive oxygen species or increasing temperature. Great strides have been made in understanding biological effects of PDT PTT at the cellular, vascular tumor microenvironmental levels, as well translating both modalities clinic. Emerging evidence suggests that may synergize due their different mechanisms action, nonoverlapping toxicity profiles make such combination potentially efficacious. Moreover, PDT/PTT combinations gained momentum recent years development multimodal nanoplatforms simultaneously incorporate photodynamically- photothermally active agents. In this review, we discuss how combining can address limitations each modality alone enhance treatment safety efficacy. We provide an overview literature featuring dual nanoparticles analyze strengths various nanoparticle design strategies. also detail sequence dose affect cellular states, pathophysiology drug delivery, ultimately shaping response. Lastly, common experimental pitfalls complicate preclinical assessment propose rational guidelines elucidate underlying interactions.

Language: Английский

Citations

537
Engineered exosomes from different sources for cancer-targeted therapy DOI Creative Commons
Menghui Zhang,

Shengyun Hu,

Lin Liu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 15, 2023

Exosome is a subgroup of extracellular vesicles, which has been serving as an efficient therapeutic tool for various diseases. Engineered exosomes are the sort modified with surface decoration and internal molecules. After appropriate modification, engineered able to deliver antitumor drugs tumor sites efficiently precisely fewer treatment-related adverse effects. However, there still exist many challenges clinical translation exosomes. For instance, what sources modification strategies could endow most activity poorly understood. Additionally, how choose appropriately in different therapies another unresolved problem. In this review, we summarized characteristics exosomes, especially spatial temporal properties. concluded recent advances cancer fields, including sources, isolation technologies, strategies, labeling imaging methods Furthermore, applications were summarized, such photodynamic therapy, gene immunotherapy. Consequently, above provides researchers community latest ideas on exosome new direction drug development, prospective accelerate cancer-targeted therapy.

Language: Английский

Citations

209
Photocatalytic Superoxide Radical Generator that Induces Pyroptosis in Cancer Cells DOI
Le Yu, Yunjie Xu,

Zhongji Pu

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(25), P. 11326 - 11337

Published: June 16, 2022

Pyroptosis, a newly characterized form of immunogenic cell death, is attracting increasing attention as promising approach to cancer immunotherapy. However, biocompatible strategies activate pyroptosis remain rare. Here, we show that photocatalytic superoxide radical (O2-•) generator, NI-TA, triggers in cells. NI-TA was designed take advantage an intramolecular triplet-ground state splitting energy modulation approach. Detailed studies revealed the triggered by under conditions photoexcitation proceeds through caspase-3/gasdermin E (GSDME) pathway rather than via canonical processes involving caspase-1/gasdermin-D (GSDMD). found function partial-O2-recycling mode action and trigger provide for effective ablation even hypoxia (≤2% O2). In case T47D 3D multicellular spheroids, good antitumor efficiency stemness inhibition are achieved. This work highlights how chemistry may be leveraged develop pyroptosis-inducing agents.

Language: Английский

Citations

178
The design of small-molecule prodrugs and activatable phototherapeutics for cancer therapy DOI Creative Commons
Hai‐Hao Han, Han-Min Wang, Paramesh Jangili

et al.

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(3), P. 879 - 920

Published: Jan. 1, 2023

This tutorial review provides a general overview for the design of prodrugs and activatable phototherapeutics which enables development improved therapies.

Language: Английский

Citations

157
Copper Doped Carbon Dots for Addressing Bacterial Biofilm Formation, Wound Infection, and Tooth Staining DOI

Meng Liu,

Ling Huang, Xingyi Xu

et al.

ACS Nano, Journal Year: 2022, Volume and Issue: 16(6), P. 9479 - 9497

Published: June 17, 2022

Oral infectious diseases and tooth staining, the main challenges of dental healthcare, are inextricably linked to microbial colonization formation pathogenic biofilms. However, dentistry has so far still lacked simple, safe, universal prophylactic options therapy. Here, we report copper-doped carbon dots (Cu-CDs) that display enhanced catalytic (catalase-like, peroxidase-like) activity in oral environment for inhibiting initial bacteria (Streptococcus mutans) adhesion subsequent biofilm eradication without impacting surrounding tissues via oxygen (O2) reactive species (ROS) generation. Especially, Cu-CDs exhibit strong affinity lipopolysaccharides (LPS) peptidoglycans (PGN), thus conferring them with excellent antibacterial ability against Gram-positive (Staphylococcus aureus) Gram-negative (Escherichia coli), such they can prevent wound purulent infection promoting rapid healing. Additionally, Cu-CDs/H2O2 system shows a better performance whitening, compared results obtained other alternatives, e.g., CDs clinically used H2O2, particularly its negligible enamel dentin destruction. It is anticipated biocompatible presented this work promising nano-mouthwash eliminating biofilms, prompting healing as well highlighting their significance health management.

Language: Английский

Citations

138
A host–guest strategy for converting the photodynamic agents from a singlet oxygen generator to a superoxide radical generator DOI Creative Commons
Kun‐Xu Teng, Li‐Ya Niu, Qing‐Zheng Yang

et al.

Chemical Science, Journal Year: 2022, Volume and Issue: 13(20), P. 5951 - 5956

Published: Jan. 1, 2022

A supramolecular strategy is reported for converting the conventional photodynamic agents from a singlet oxygen generator to superoxide radical by host–guest interaction enhanced electron transfer.

Language: Английский

Citations

131
From Low to No O2-Dependent Hypoxia Photodynamic Therapy (hPDT): A New Perspective DOI
Mingle Li, Yunjie Xu, Xiaojun Peng

et al.

Accounts of Chemical Research, Journal Year: 2022, Volume and Issue: 55(22), P. 3253 - 3264

Published: Nov. 2, 2022

ConspectusThe advent of photochemical techniques has revolutionized the landscape biology and medical sciences. Especially appealing in this context is photodynamic therapy (PDT), which a photon-initiated treatment modality that uses cytotoxic reactive oxygen species (ROS) to kill malignant cells. In past decade, PDT risen forefront cancer therapy. Its optical control enables noninvasive spatiotemporal manipulation process, its photoactive nature allows unique patterns avoid drug resistance conventional chemotherapeutics. However, despite impressive advances field, achieving widespread clinical adoption remains difficult. A major concern hostile tumor microenvironment, cells are hypoxic, hinders ROS generation during action. To overcome "Achilles' heel", current strategies focus primarily on improvement intratumoral O2 perfusion, while trials suggest enrichment may promote cell proliferation metastasis, thereby making FDA approval transformation these paradigms challenging.In an effort improve hypoxia (hPDT) clinic, we have explored "low no O2-dependent" approaches over years combat hypoxia-induced resistance. Account, present our contributions theme 5 years, beginning with low O2-dependent (e.g., type I superoxide radical (O2•–) generator, O2-economizer, mitochondrial respiration inhibition, cellular self-protective pathway modulation, etc.) progressing O2-independent autoadaptive PDT/PTT complementary therapy, artificial photoredox catalysis cells). These studies attracted tremendous attention. Particularly pioneering work 2018, presented first demonstration O2•–-mediated partial O2-recyclability mechanism can ( J. Am. Chem. Soc. 140, 14851−14859). This launched era renewed interest PDT, resulting plethora new O2•– photogenerators developed by many groups around world. Moreover, discovery reactions living cells, emerged as field connecting photochemistry biomedicine, stimulating development next-generation phototherapeutic tools 2022, 144, 163−173). Our recent also disclosed "photoredox cells" might be general action Proc. Natl. Acad. Sci. U.S.A. 119, e2210504119). emergent concepts, molecular designs, mechanisms, applications diagnosis therapeutics, well pros cons, discussed depth Account. It expected date will use researchers inspire future efforts identify more promising hPDT better meet needs

Language: Английский

Citations

106
Porous organic polymers for drug delivery: hierarchical pore structures, variable morphologies, and biological properties DOI

Yunxin Tang,

Anuraj Varyambath,

Yuanchen Ding

et al.

Biomaterials Science, Journal Year: 2022, Volume and Issue: 10(19), P. 5369 - 5390

Published: Jan. 1, 2022

Porous organic polymers have received considerable attention in recent years because of their applicability as biomaterials.

Language: Английский

Citations

103
Engineering of BODIPY-based theranostics for cancer therapy DOI
Zhiqiang Mao, Ji Hyeon Kim, Jieun Lee

et al.

Coordination Chemistry Reviews, Journal Year: 2022, Volume and Issue: 476, P. 214908 - 214908

Published: Nov. 7, 2022

Language: Английский

Citations

101
Current advance of nanotechnology in diagnosis and treatment for malignant tumors DOI Creative Commons

Bilan Wang,

Shiqi Hu, Yan Teng

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Aug. 12, 2024

Cancer remains a significant risk to human health. Nanomedicine is new multidisciplinary field that garnering lot of interest and investigation. shows great potential for cancer diagnosis treatment. Specifically engineered nanoparticles can be employed as contrast agents in diagnostics enable high sensitivity high-resolution tumor detection by imaging examinations. Novel approaches labeling are also made possible the use nanoprobes nanobiosensors. The achievement targeted medication delivery therapy accomplished through rational design manufacture nanodrug carriers. Nanoparticles have capability effectively transport medications or gene fragments tissues via passive active targeting processes, thus enhancing treatment outcomes while minimizing harm healthy tissues. Simultaneously, context radiation sensitization photothermal enhance therapeutic efficacy malignant tumors. This review presents literature overview summary how nanotechnology used According oncological diseases originating from different systems body combining pathophysiological features cancers at sites, we most recent developments applications. Finally, briefly discuss prospects challenges cancer.

Language: Английский

Citations

87