Engineered drug-protein nanoparticle complexes for folate receptor targeting

Area of Science:

• Biotechnology
• Nanomedicine
• Protein Engineering

Background:

• Therapeutic nanomaterials require high uniformity and functionality, which are challenging to achieve with traditional methods.
• Recombinant synthesis offers biological precision for fabricating advanced nanomaterials.

Purpose of the Study:

• To engineer protein nanoparticles with optical imaging, drug delivery, and tumor-targeting capabilities using a recombinant protein scaffold.
• To demonstrate simultaneous acid-labile drug release and folate receptor targeting on these novel nanoparticles.

Main Methods:

• Engineered ~27-nm dodecahedral protein nanoparticles using the E2 subunit of pyruvate dehydrogenase (D381C variant).
• Conjugated Alexa Fluor 532 (AF532) and doxorubicin (DOX) to the internal cavity.
• Functionalized the external surface with polyethylene glycol (PEG) and/or folic acid (FA) for targeting.

Main Results:

• Engineered nanoparticles maintained structural integrity and assembly.
• FA-displaying nanoparticles showed a six-fold increase in cellular uptake by folate receptor-overexpressing cells, confirming FA-specific targeting.
• DOX-loaded nanoparticles exhibited cytotoxicity in the low micromolar range.

Conclusions:

• Biofabrication strategies can yield functional nanomaterials with integrated therapeutic capabilities.
• This study presents the first instance of combining acid-labile drug release and folate receptor targeting on recombinant protein nanoparticles.
• These engineered nanoparticles hold significant potential for targeted cancer therapy and diagnostics.