Genetically encoded self-assembling affibody-streptavidin nanoparticles for HER2-positive cancer theranostics

Area of Science:

• Biotechnology
• Nanomedicine
• Oncology

Background:

• Targeted cancer therapies like antibody-drug conjugates (ADCs) and immunotoxins offer precision but involve complex, costly chemical synthesis.
• Existing nanoparticle systems also face challenges with multi-step, poorly reproducible production methods.

Purpose of the Study:

• To introduce a novel, genetically encoded, self-assembling protein nanoparticle platform for targeted cancer therapy.
• To overcome the limitations of chemical conjugation and complex synthesis in current targeted biotherapeutics.

Main Methods:

• Engineered a fusion protein (ZHER2:342-Strp) encoding an HER2-specific affibody and streptavidin for self-assembly into "avisomes".
• Synthesized avisomes in E. coli and confirmed HER2 targeting using flow cytometry and fluorescence microscopy.
• Loaded avisomes with doxorubicin (DOX) to create cytotoxic ZHER2:342-Strp-DOX nanoparticles for in vitro and in vivo studies.

Main Results:

• ZHER2:342-Strp-DOX nanoparticles selectively killed HER2-overexpressing cancer cells in vitro.
• In vivo studies showed significant suppression of HER2-positive tumor growth in mice.
• Therapy was well-tolerated, with no adverse hematological or biochemical changes, and mitigated doxorubicin-induced neutropenia.

Conclusions:

• Avisomes represent a highly promising, genetically encoded, self-assembling theranostic platform for HER2-positive breast cancer.
• This approach offers a scalable, reproducible, and cost-efficient alternative to ADCs and synthetic nanoparticles for next-generation cancer therapy.