Stimuli-Sensitive Linear-Dendritic Block Copolymer-Drug Prodrug as a Nanoplatform for Tumor Combination Therapy

Stimuli-Sensitive Linear-Dendritic Block Copolymer-Drug Prodrug as a Nanoplatform for Tumor Combination Therapy

© 2022 Wiley-VCH GmbH.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 34(2022), 8 vom: 15. Feb., Seite e2108049
1. Verfasser: Cai, Hao (VerfasserIn)
Weitere Verfasser: Tan, Ping, Chen, Xiaoting, Kopytynski, Michal, Pan, Dayi, Zheng, Xiuli, Gu, Lei, Gong, Qiyong, Tian, Xiaohe, Gu, Zhongwei, Zhang, Hu, Chen, Rongjun, Luo, Kui
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2022
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article amphiphilic polymers combination therapy linear-dendritic block copolymers nanomedicine tumor-microenvironment-responsive polymers Photosensitizing Agents Porphyrins Prodrugs Doxorubicin 80168379AG
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520 |a Linear-dendritic block copolymer (LDBCs) are highly attractive candidates for smart drug-delivery vehicles. Herein, an amphiphilic poly[(ethylene glycol) methyl ether methacrylate] (POEGMA) linear-peptide dendritic prodrug of doxorubicin (DOX) prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization is reported. The hydrophobic-dye-based photosensitizer chlorin e6 (Ce6) is employed for encapsulation in the prodrug nanoparticles (NPs) to obtain an LDBCs-based drug-delivery system (LD-DOX/Ce6) that offers a combination cancer therapy. Due to the presence of Gly-Phe-Leu-Gly peptides and hydrazone bonds in the prodrug structure, LD-DOX/Ce6 is degraded into small fragments, thus specifically triggering the intracellular release of DOX and Ce6 in the tumor microenvironment. Bioinformatics analysis suggests that LD-DOX/Ce6 with laser irradiation treatment significantly induces apoptosis, DNA damage, and cell cycle arrest. The combination treatment can not only suppress tumor growth, but also significantly reduce tumor metastasis compared with treatments with DOX or Ce6 through regulating EMT pathway, TGFβ pathway, angiogenesis, and the hypoxia pathway. LD-DOX/Ce6 displays a synergistic chemo-photodynamic antitumor efficacy, resulting in a high inhibition in tumor growth and metastasis, while maintaining an excellent biosafety. Therefore, this study demonstrates the potential of the biodegradable and tumor-microenvironment-responsive LDBCs as an intelligent multifunctional drug-delivery vehicle for high-efficiency cancer combination therapy 
650 4 |a Journal Article 
650 4 |a amphiphilic polymers 
650 4 |a combination therapy 
650 4 |a linear-dendritic block copolymers 
650 4 |a nanomedicine 
650 4 |a tumor-microenvironment-responsive polymers 
650 7 |a Photosensitizing Agents  |2 NLM 
650 7 |a Porphyrins  |2 NLM 
650 7 |a Prodrugs  |2 NLM 
650 7 |a Doxorubicin  |2 NLM 
650 7 |a 80168379AG  |2 NLM 
700 1 |a Tan, Ping  |e verfasserin  |4 aut 
700 1 |a Chen, Xiaoting  |e verfasserin  |4 aut 
700 1 |a Kopytynski, Michal  |e verfasserin  |4 aut 
700 1 |a Pan, Dayi  |e verfasserin  |4 aut 
700 1 |a Zheng, Xiuli  |e verfasserin  |4 aut 
700 1 |a Gu, Lei  |e verfasserin  |4 aut 
700 1 |a Gong, Qiyong  |e verfasserin  |4 aut 
700 1 |a Tian, Xiaohe  |e verfasserin  |4 aut 
700 1 |a Gu, Zhongwei  |e verfasserin  |4 aut 
700 1 |a Zhang, Hu  |e verfasserin  |4 aut 
700 1 |a Chen, Rongjun  |e verfasserin  |4 aut 
700 1 |a Luo, Kui  |e verfasserin  |4 aut 
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773 1 8 |g volume:34  |g year:2022  |g number:8  |g day:15  |g month:02  |g pages:e2108049 
856 4 0 |u http://dx.doi.org/10.1002/adma.202108049  |3 Volltext 
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