Integrating Proteolysis‐Targeting Chimeras (PROTACs) with Delivery Systems for More Efficient and Precise Targeted Protein Degradation DOI

Jiachan Lin,

Zirui Chen, Dan Zhang

и другие.

Macromolecular Rapid Communications, Год журнала: 2025, Номер unknown

Опубликована: Апрель 4, 2025

Targeted protein degradation (TPD) using the proteolysis-targeting chimeras (PROTACs) is emerging as a revolutionary technology, offering potential strategy for cancer treatment by inducing of overexpressed oncogenic proteins in tumors. PROTACs function recruiting E3 ligases and utilizing ubiquitin-proteasome pathway (UPS) to catalyze target proteins. Compared traditional small molecules inhibitors, exhibit enhanced selectivity, ability overcome drug resistance, traditionally deemed "undruggable". However, poor water solubility low cellular permeability significantly limit their pharmacokinetic properties, while systemic toxicity may hinder clinical application. To address these limitations, strategies that integrate with delivery systems are gaining attention. This review summarizes latest advancements various enhance vivo efficacy reduce off-target effects PROTACs, including prototype nanoparticles, covalent modification-based prodrug strategies, innovative multi-headed designs, microneedle systems, discussing design principles associated challenges. The combination potent multifunctional holds promise accelerating translation improving therapeutic treatment.

Язык: Английский

A PROTAC Augmenter for Photo‐Driven Pyroptosis in Breast Cancer DOI

Daipeng Huang,

Yang Zou,

Haiqiao Huang

и другие.

Advanced Materials, Год журнала: 2024, Номер 36(21)

Опубликована: Фев. 16, 2024

Proteolysis targeting chimera (PROTAC) has recently emerged as a promising strategy for inducing post-translational knockdown of target proteins in disease treatment. The degradation bromodomain-containing protein 4 (BRD4), an essential nuclear gene transcription, induced by PROTAC is proposed epigenetic approach to treat breast cancer. However, the poor membrane permeability and indiscriminate distribution vivo results low bioavailability, limiting its development application. Herein, nano "targeting chimera" (abbreviated L@NBMZ) consisting BRD4-PROTAC combined with photosensitizer, serve first augmenter photo-driven pyroptosis cancer, developed. With excellent BRD4 ability, high biosafety, biocompatibility, L@NBMZ blocks transcription degrading through proteasomes vivo, surprisingly, induces cleavage caspase-3. This type caspase-3 synergistically amplified light irradiation presence photosensitizers, leading efficient pyroptosis. Both vitro outcomes demonstrate remarkable anti-cancer efficacy this augmenter, which significantly inhibits lung metastasis cancer vivo. Thus, photo-PROTAC construction may pave new way expanding applications within paradigms.

Язык: Английский

Процитировано

14

Unleashing the power of immune checkpoints: Post-translational modification of novel molecules and clinical applications DOI
Jie Wang, Yian Wang,

Xianjie Jiang

и другие.

Cancer Letters, Год журнала: 2024, Номер 588, С. 216758 - 216758

Опубликована: Фев. 22, 2024

Язык: Английский

Процитировано

14

Eosinophil‐Activating Semiconducting Polymer Nanoparticles for Cancer Photo‐Immunotherapy DOI
Chi Zhang, Jingsheng Huang,

Mengke Xu

и другие.

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(30)

Опубликована: Май 3, 2024

Eosinophils are important immune effector cells that affect T cell-mediated antitumor immunity. However, the low frequency and restrained activity of eosinophils restricted outcome cancer immunotherapies. We herein report an eosinophil-activating semiconducting polymer nanoparticle (SPNe) to improve photodynamic tumor immunogenicity, modulate eosinophil chemotaxis, reinvigorate T-cell immunity for activated photo-immunotherapy. SPNe comprises amphiphilic a dipeptidyl peptidase 4 (DPP4) inhibitor sitagliptin via

Язык: Английский

Процитировано

11

Two-dimensional nano-biomaterials in regulating the tumor microenvironment for immunotherapy DOI Creative Commons
Guangyu Xu, Jie Li,

Suming Zhang

и другие.

Nano TransMed, Год журнала: 2024, Номер 3, С. 100045 - 100045

Опубликована: Авг. 24, 2024

Язык: Английский

Процитировано

11

Integrating Proteolysis‐Targeting Chimeras (PROTACs) with Delivery Systems for More Efficient and Precise Targeted Protein Degradation DOI

Jiachan Lin,

Zirui Chen, Dan Zhang

и другие.

Macromolecular Rapid Communications, Год журнала: 2025, Номер unknown

Опубликована: Апрель 4, 2025

Targeted protein degradation (TPD) using the proteolysis-targeting chimeras (PROTACs) is emerging as a revolutionary technology, offering potential strategy for cancer treatment by inducing of overexpressed oncogenic proteins in tumors. PROTACs function recruiting E3 ligases and utilizing ubiquitin-proteasome pathway (UPS) to catalyze target proteins. Compared traditional small molecules inhibitors, exhibit enhanced selectivity, ability overcome drug resistance, traditionally deemed "undruggable". However, poor water solubility low cellular permeability significantly limit their pharmacokinetic properties, while systemic toxicity may hinder clinical application. To address these limitations, strategies that integrate with delivery systems are gaining attention. This review summarizes latest advancements various enhance vivo efficacy reduce off-target effects PROTACs, including prototype nanoparticles, covalent modification-based prodrug strategies, innovative multi-headed designs, microneedle systems, discussing design principles associated challenges. The combination potent multifunctional holds promise accelerating translation improving therapeutic treatment.

Язык: Английский

Процитировано

1