Tuning the Structure of Poly(aspartic acid)s' Self-Assemblies to Enhance Cellular Uptake

Area of Science:

• Materials Science
• Biotechnology
• Nanotechnology

Background:

• Amphiphilic block or graft copolymers form self-assembled nanoparticles for drug delivery.
• Controlling nanoparticle structure is key to enhancing cellular uptake.

Purpose of the Study:

• To explore a novel strategy for tuning nanoparticle structure.
• To enhance cellular uptake by varying the hydrophilic ratio of amphiphilic graft copolymers.

Main Methods:

• Synthesized poly(aspartic acid) substituted with octadecyl chains at varying degrees of substitution (DS).
• Investigated morphological transitions (spherical, rod-like, vesicular, lamellar-like) with increasing DS.
• Incorporated Trans-Activator of Transcription (TAT) peptide to enhance cellular uptake.

Main Results:

• Morphology transitioned from spherical to rod-like, vesicular, and lamellar-like structures with increasing DS.
• TAT peptide conjugation significantly enhanced cellular uptake.
• Lamellar-like self-assemblies showed a 1.3-fold increase in cellular uptake compared to spherical and a 3.6-fold increase compared to vesicles.

Conclusions:

• Tuning the structure of poly(aspartic acid) self-assemblies is an effective strategy to enhance cellular uptake.
• This approach improves cell penetrating activity for targeted drug delivery while minimizing cell damage.
• The findings offer a new method for developing advanced drug delivery systems.