PEG-polypeptide block copolymers as pH-responsive endosome-solubilizing drug nanocarriers

Area of Science:

• Biomaterials Science
• Nanotechnology
• Polymer Chemistry

Background:

• Developing effective drug delivery systems is crucial for cancer therapy.
• pH-sensitive polymers offer targeted drug release mechanisms.
• Polypeptide-based block copolymers are promising for nanomedicine.

Purpose of the Study:

• To create pH-sensitive nanoscale drug delivery systems using click chemistry-modified polypeptide-based block copolymers.
• To investigate the self-assembly and pH-responsive disassembly of these copolymers.
• To evaluate their efficacy in vitro and in vivo for cancer treatment.

Main Methods:

• Synthesis of PEG-polypeptide copolymers via N-carboxyanhydride polymerization and post-functionalization.
• Utilizing azide-alkyne cycloaddition (click chemistry) for modification.
• Characterization of self-assembly into polymersomes and their pH-dependent behavior.
• In vitro drug encapsulation and release studies.
• In vivo studies using a mouse model for triple-negative breast cancer.

Main Results:

• Successfully synthesized polypeptide-based block copolymers with amine side groups.
• Demonstrated self-assembly into stable, pH-sensitive polymersomes.
• Polymersomes effectively encapsulated hydrophilic drugs (e.g., doxorubicin) at physiological pH.
• Showed spontaneous disassembly at endosomal pH, facilitating intracellular drug release.
• Achieved significant tumor accumulation and demonstrated efficacy against MDA-MB-468 cells in vivo, suppressing tumor growth.

Conclusions:

• Click chemistry-modified polypeptide-based block copolymers are effective for fabricating pH-sensitive drug delivery systems.
• These polymersomes offer a promising platform for targeted cancer therapy due to their responsive disassembly.
• The developed system shows potential for improved efficacy and reduced systemic toxicity in cancer treatment.