Polypeptide-based nanocarriers from aqueous ROPISA: Shape-dependent performance in colorectal and breast cancer...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery

Background:

• Polypeptide nanocarriers are crucial for drug delivery.
• The impact of nanocarrier morphology on performance is not well understood.

Purpose of the Study:

• To develop a novel method for synthesizing polypeptide nanocarriers with varying morphologies.
• To compare the cellular uptake and in vivo biodistribution of worm-like versus spherical nanocarriers.

Main Methods:

• Synthesized fluorescent worm-like nanoparticles via one-step aqueous ring-opening polymerization-induced self-assembly (ROPISA) of γ-benzyl-l-glutamate N-carboxyanhydride (BLG-NCA).
• Prepared spherical analogues using solvent displacement.
• Evaluated nanoparticle internalization in CT26 and 4T1 cancer cell lines (2D and 3D spheroids).
• Assessed in vivo biodistribution and tumor accumulation in mouse models.

Main Results:

• Both worm-like and spherical nanoparticles were efficiently internalized by cancer cells.
• Faster uptake was observed in CT26 cells, while higher accumulation occurred in 4T1 cells.
• Nanoparticles penetrated 3D spheroids, with slower diffusion but higher final accumulation in 4T1 spheroids.
• In vivo studies showed prolonged circulation and significant tumor accumulation, particularly in 4T1 tumors.

Conclusions:

• ROPISA of NCA is a versatile platform for creating polypeptide nanocarriers.
• Nanoparticle morphology influences cellular uptake and tumor accumulation dynamics.
• These findings support the development of advanced nanomedicines for targeted drug delivery.