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

Area of Science:

• Biotechnology
• Protein Engineering
• Nanomedicine

Background:

• Therapeutic proteins often have short in vivo half-lives, necessitating frequent high-dose injections.
• This leads to poor patient outcomes, adverse effects, high costs, and low compliance.
• Developing strategies to prolong protein half-life and improve targeting is crucial.

Purpose of the Study:

• To engineer a fusion protein that self-assembles into nanoparticles.
• To enhance the in vivo half-life and tumor-targeting ability of trichosanthin (TCS).
• To create a pH-responsive system for improved therapeutic protein delivery.

Main Methods:

• Genetic fusion of trichosanthin (TCS) with the Sup35p prion domain (Sup35) to create TCS-Sup35.
• Self-assembly of TCS-Sup35 into uniform spherical nanoparticles (TCS-Sup35 NP).
• Evaluation of in vivo half-life, tumor accumulation, and antitumor efficacy in mouse models.

Main Results:

• TCS-Sup35 self-assembled into nanoparticles (TCS-Sup35 NP) with retained TCS bioactivity.
• TCS-Sup35 NP exhibited a 21.5-fold longer in vivo half-life compared to native TCS.
• Enhanced tumor accumulation and significant antitumor activity with no detectable systemic toxicity.

Conclusions:

• Self-assembling and pH-responsive protein fusion is a viable strategy to improve therapeutic protein performance.
• This approach offers a simple, generalizable solution for proteins with short circulation half-lives.
• The developed nanoparticles show potential for improved cancer therapy and patient compliance.