Details

Autor(en) / Beteiligte

• Cai, Hao
• Tan, Ping
• Chen, Xiaoting
• Kopytynski, Michal
• Pan, Dayi
• Zheng, Xiuli
• Gu, Lei
• Gong, Qiyong
• Tian, Xiaohe
• Gu, Zhongwei
• Zhang, Hu
• Chen, Rongjun
• Luo, Kui

Titel

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

Ist Teil von

• Advanced materials (Weinheim), 2022-02, Vol.34 (8), p.e2108049-n/a

Ort / Verlag

Germany: Wiley Subscription Services, Inc

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. A linear–dendritic block copolymer prodrug with enzyme and pH dual‐responsiveness is synthesized through a new synthesis strategy. The prodrug and photosensitizer chlorin e6 (Ce6) self‐assemble to form nanoparticles for efficient drug delivery and controlled release drug. Doxorubicin (DOX) and Ce6 exert a synergistic antitumor effect by intensifying cell DNA damage and activating apoptotic pathways, resulting in an excellent antitumor effect.