Self-assembling and pH-responsive protein nanoparticle as potential platform for targeted tumor therapy

被引:3
作者
Xu, Zhikun [1 ]
Zhang, Xiaozhan [1 ]
Dong, Wang [1 ]
Lv, Huifang [1 ]
Zuo, Lijie [1 ]
Zhu, Lifei [1 ]
Wang, Ruining [1 ]
Ma, Xia [1 ]
机构
[1] Henan Univ Anim Husb & Econ, Coll Vet Med, Zhengzhou, Peoples R China
关键词
trichosanthin; self-assembly; pH-Responsive; protein nanoparticle; tumor targeting; TRICHOSANTHIN; PEGYLATION;
D O I
10.3389/fmolb.2023.1172100
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Frequent injections at high concentrations are often required for many therapeutic proteins due to their short in vivo half-life, which usually leads to unsatisfactory therapeutic outcomes, adverse side effects, high cost, and poor patient compliance. Herein we report a supramolecular strategy, self-assembling and pH regulated fusion protein to extend the in vivo half-life and tumor targeting ability of a therapeutically important protein trichosanthin (TCS). TCS was genetically fused to the N-terminus of a self-assembling protein, Sup35p prion domain (Sup35), to form a fusion protein of TCS-Sup35 that self-assembled into uniform spherical TCS-Sup35 nanoparticles (TCS-Sup35 NP) rather than classic nanofibrils. Importantly, due to the pH response ability, TCS-Sup35 NP well retained the bioactivity of TCS and possessed a 21.5-fold longer in vivo half-life than native TCS in a mouse model. As a result, in a tumor-bearing mouse model, TCS-Sup35 NP exhibited significantly improved tumor accumulation and antitumor activity without detectable systemic toxicity as compared with native TCS. These findings suggest that self-assembling and pH responding protein fusion may provide a new, simple, general, and effective solution to remarkably improve the pharmacological performance of therapeutic proteins with short circulation half-lives.
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页数:9
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