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Protein nanogels with enhanced pH-responsive dynamics triggered by remote NIR for systemic protein delivery and
Xican Zhang1, Pan Zhou1, Shijie Zhuo1
1Clinical Translational Center for Targeted Drugs, Department of Pharmacology, School of Medicine, Jinan University, Guangzhou 510632, Guangdong Province, China.
International Journal of Pharmaceutics
|June 27, 2021
Summary
Researchers developed a pH-responsive nanogel for efficient protein delivery. This nanogel protects therapeutic proteins from degradation and enables controlled release using near-infrared light, improving cancer treatment potential.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Drug Delivery
Background:
- Therapeutic proteins offer significant medical potential but face challenges with in vivo degradation and denaturation.
- Current protein delivery systems struggle with efficient systemic delivery and controlled release.
- Biocompatible formulations are crucial for overcoming native protein limitations.
Purpose of the Study:
- To develop a novel pH-responsive nanogel for efficient encapsulation and systemic delivery of therapeutic proteins.
- To engineer a system for controlled protein release triggered by environmental stimuli and external triggers.
- To enhance protein-based cancer therapy through improved delivery and release mechanisms.
Main Methods:
- Self-assembly of a pH-responsive nanogel (PI825@PDC/protein NGs) using 6-arm PEGylated crystalline β-cyclodextrin (β-CD) and IR825 dye.
- Encapsulation of proteins within the nanogel structure via host-guest interactions.
- Utilizing a pH-responsive 2,3-dimethylmaleic anhydride (DMA) linker for controlled dissociation and protein release.
- Employing near-infrared (NIR) irradiation to enhance release dynamics through localized heating.
Main Results:
- Achieved highly efficient protein encapsulation within the robust nanogel structure.
- Demonstrated nanogel stability under various physiological conditions (in vitro and in vivo).
- Showcased pH-dependent protein release, further enhanced by NIR-triggered hyperthermia for programmable release.
- Validated the potential for improved protein delivery and cancer treatment.
Conclusions:
- Developed a versatile and efficient method for loading proteins into nanogels for systemic delivery.
- Established a programmable protein release system activated by remote NIR irradiation.
- The pH-responsive nanogel system offers significant potential for protein engineering and advanced medical applications, particularly in cancer therapy.
