Targeted Radionuclide Therapy Activates Prodrugs for Treating Metastasis DOI Creative Commons
Zhibin Guo, Xuanyu Wang, Yi Han

et al.

ACS Central Science, Journal Year: 2024, Volume and Issue: 10(12), P. 2321 - 2330

Published: Dec. 5, 2024

Over 90% of cancer patients succumb to metastasis, yet conventional frontline therapy struggles halt the progression metastatic tumors. Targeted radionuclide therapy, which delivers radiation precisely tumor sites, shows promise for treating metastasis. The rational design a prodrug activation platform using radionuclides would be an ideal approach synergize chemotherapy with targeted it has not been established. Here, we present therapy-induced cleavage chemistry that enables controlled release oxaliplatin and its axis ligands from oxaliplatin(IV) complexes in living systems. Of note, this strategy demonstrates feasibility over clinically relevant β-emitting exhibits dose dependence. These advantages were taken into account, Lutetium-177-activatable platinum(IV) based system was designed could achieve localized at site high efficiency, thereby suppressing subcutaneous 4T1 In summary, our highlights potential as reaction switches, bridging gap between radiotherapy-induced internal radiation. It may provide new perspective future combination therapy.

Language: Английский

Radiotherapy activates picolinium prodrugs in tumours DOI
Qunfeng Fu, 知子 谷, Siyong Shen

et al.

Nature Chemistry, Journal Year: 2024, Volume and Issue: 16(8), P. 1348 - 1356

Published: April 1, 2024

Language: Английский

Citations

25
Radiopharmaceuticals and their applications in medicine DOI Creative Commons
Siqi Zhang, Xingkai Wang, Xin Gao

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 2, 2025

Abstract Radiopharmaceuticals involve the local delivery of radionuclides to targeted lesions for diagnosis and treatment multiple diseases. Radiopharmaceutical therapy, which directly causes systematic irreparable damage cells, has attracted increasing attention in refractory diseases that are not sensitive current therapies. As Food Drug Administration (FDA) approvals [ 177 Lu]Lu-DOTA-TATE, Lu]Lu-PSMA-617 their complementary diagnostic agents, namely, 68 Ga]Ga-DOTA-TATE Ga]Ga-PSMA-11, radiopharmaceutical-based theranostics (radiotheranostics) being increasingly implemented clinical practice oncology, lead a new era radiopharmaceuticals. The generation radiopharmaceuticals utilizes targeting vector achieve accurate avoid off-target deposition, making it possible improve efficiency biosafety tumour therapy. Numerous studies have focused on developing novel broader range disease targets, demonstrating remarkable vivo performance. These include high tumor uptake, prolonged retention time, favorable pharmacokinetic properties align with standards. While radiotheranostics been widely applied applications now expanding neurodegenerative diseases, cardiovascular inflammation. Furthermore, radiotheranostic-empowered precision medicine is revolutionizing cancer paradigm. Diagnostic play pivotal role patient stratification planning, leading improved therapeutic outcomes radionuclide This review offers comprehensive overview evolution radiopharmaceuticals, including both FDA-approved clinically investigated explores mechanisms cell death induced by It emphasizes significance future prospects theranostic-based advancing medicine.

Language: Английский

Citations

7
Prodrug-based bispecific antibodies for cancer therapy: advances and future directions DOI Creative Commons

Zhengdong Ai,

Bing Wang,

Yunlong Song

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 22, 2025

Bispecific antibodies represent an innovative paradigm in cancer therapy, offering broader therapeutic potential compared to conventional monoclonal antibodies. To increase tumor selectivity while mitigating off-target effects normal tissues, the concept of prodrug-based bispecific has emerged. This review delineates various mechanisms underlying action antibodies, including protease-mediated activation, steric hindrance release via proteolytic processing, activation by soluble factors, conditional assembly, and chain exchange-mediated activation. We also address critical challenges that must be overcome optimize development clinical application these sophisticated agents.

Language: Английский

Citations

2
Nitric Oxide‐Activated Bioorthogonal Codelivery Nanoassembly for In Situ Synthesis of Photothermal Agent for Precise and Safe Anticancer Treatment DOI
Bowen Li,

Jianwu Tian,

Chongzhi Wu

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(33)

Published: June 17, 2024

The development of bioorthogonal activation in drug release represents a promising avenue for precise and safe anticancer treatment. However, two significant limitations currently hinder their clinical application: i) the necessity separate administration precursor its corresponding activator, leading to poor accumulation potential side effects; ii) reliance on exogenous metal or organic activators triggering activation, which often exhibit low efficiency systemic toxicity when extending living animals. To overcome these limitations, nitric oxide (NO)-mediated codelivery nanoassembly, termed TTB-NH

Language: Английский

Citations

9
Breaking Barriers: Nanomedicine-Based Drug Delivery for Cataract Treatment DOI Creative Commons
Yilin Chen, Zi Ye, Haixu Chen

et al.

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 4021 - 4040

Published: May 1, 2024

Abstract: Cataract is a leading cause of blindness globally, and its surgical treatment poses significant burden on global healthcare. Pharmacologic therapies, including antioxidants protein aggregation reversal agents, have attracted great attention in the cataracts recent years. Due to anatomical physiological barriers eye, effectiveness traditional eye drops for delivering drugs topically lens hindered. The advancements nanomedicine present novel promising strategies addressing challenges drug delivery lens, development nanoparticle formulations that can improve penetration into anterior segment enable sustained release medications. This review introduces various cutting-edge systems cataract treatment, highlighting their physicochemical properties surface engineering optimal design, thus providing impetus further innovative research potential clinical applications anti-cataract drugs. Keywords: nanomedicine, cataract, ocular barrier, system

Language: Английский

Citations

8
Cleavage of Homonuclear Chalcogen‐Chalcogen Bonds in a Hybrid Platform in Response to X‐Ray Radiation Potentiates Tumor Radiochemotherapy DOI Open Access

Yuanyuan You,

Yanzhou Chang,

Shuya Pan

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 64(1)

Published: Aug. 23, 2024

Chalcogens are used as sensitive redox-responsive reagents in tumor therapy. However, chalcogen bonds triggered by external ionizing radiation, rather than internal environmental stimuli, enable site-directed and real-time drug degradation target lesions. This approach helps to bypass chemoresistance global systemic toxicity, presenting a significant advancement over traditional chemoradiotherapy. In this study, we fabricated hybrid monodisperse organosilica nanoprodrug based on homonuclear single (disulfide (S-S, approximately 240 kJ/mol), diselenium (Se-Se, 172 tellurium (Te-Te, 126 kJ/mol)), including ditelluride-bond-bridged MONs (DTeMSNs), diselenide-bond-bridged (DSeMSNs) disulfide-bond-bridged (DSMSNs). The results demonstrated that differences electronegativities atomic radii influenced their oxidation sensitivities reactivities. Tellurium, with the lowest electronegativity, showed highest sensitivity, followed selenium sulfur. DTeMSNs exhibited highly responsive cleavage upon exposure X-rays, resulting TeO

Language: Английский

Citations

7
A self‐reinforced activatable photosensitizer prodrug enabling synergistic photodynamic and chemotherapy DOI Creative Commons

Daipeng Huang,

Jikai Yin, Yang Zou

et al.

Smart Molecules, Journal Year: 2024, Volume and Issue: unknown

Published: June 14, 2024

Abstract As a novel drug development paradigm, selective activation of prodrugs provides the potential for precise tumor chemotherapy, thereby presenting an opportunity advancing cancer treatment. The combination photodynamic therapy (PDT) and prodrug can enhance therapeutic efficacy while simultaneously enabling real‐time monitoring distribution release. However, hypoxia microenvironment frequent high‐dose administration significantly impede escalate treatment‐related risks. Herein, microenvironment‐specific release is constructed, termed NBS‐2S‐5FU. Under influence glutathione (GSH), NBS‐2S‐5FU undergoes activation, leading to photosensitizer NBS chemotherapeutic agent 5‐FU derivatives. irradiation, produces sufficient superoxide radical () derivatives inhibit DNA biosynthesis, effectively suppressing growth at low doses. Subsequent in vivo studies utilizing liposomes exhibit outstanding anti‐cancer effectiveness. This study highlights promising direction combined that integrate PDT chemotherapy.

Language: Английский

Citations

6
Locally unlocks prodrugs by radiopharmaceutical in tumor for cancer therapy DOI

Changlun Wang,

Mengxin Xu, Zihang Zhang

et al.

Science Bulletin, Journal Year: 2024, Volume and Issue: 69(17), P. 2745 - 2755

Published: July 15, 2024

Language: Английский

Citations

6
Smart Bioorthogonal Nanozymes: From Rational Design to Appropriate Bioapplications DOI
Bin Zhang, Jiawei Zhu, Jinsong Ren

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(41)

Published: Aug. 16, 2024

Abstract Bioorthogonal chemistry has provided an elaborate arsenal to manipulate native biological processes in living systems. As the great advancement of nanotechnology recent years, bioorthogonal nanozymes are innovated tackle challenges that emerged practical biomedical applications. uniquely positioned owing their advantages high customizability and tunability, as well good adaptability systems, which bring exciting opportunities for More intriguingly, offers opportunity innovating catalytic materials. In this comprehensive review, significant progresses discussed with both spatiotemporal controllability performance highlight design principles rapid The remaining future perspectives then outlined along thriving field. It is expected review will inspire promote novel nanozymes, facilitate clinical translation.

Language: Английский

Citations

6
Bioorthogonal Bond Cleavage Chemistry for On-demand Prodrug Activation: Opportunities and Challenges DOI
Qingqiang Min, Xingyue Ji

Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 66(24), P. 16546 - 16567

Published: Dec. 12, 2023

Time- and space-resolved drug delivery is highly demanded for cancer treatment, which, however, can barely be achieved with a traditional prodrug strategy. In recent years, the strategy based on bioorthogonal bond cleavage chemistry has emerged advantages of high temporospatial resolution over activation homogeneous irrespective individual heterogeneity. past five tremendous progress been witnessed in this field one such entering Phase II clinical trials. This Perspective aims to highlight these new advances (2019–2023) critically discuss their pros cons. addition, remaining challenges potential strategic directions future will also included.

Language: Английский

Citations

14