Amoozgar Zohreh, Goldberg Michael S
Department of Cancer Immunology & Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.
Nanomedicine (Lond). 2017 Apr;12(7):729-743. doi: 10.2217/nnm-2016-0375. Epub 2017 Mar 21.
We aimed to enhance the stability and therapeutic efficiency of protein-based therapeutic formulations.
MATERIALS & METHODS: Proteins were immobilized on the surface of nanoparticles (NPs) to improve both protein stability and protein function, especially enzymatic activity. The modularity of the platform was demonstrated by coating proteins of varied molecular weights and functionalities on the surface of poly(lactic-co-glycolic acid)-based NPs.
Coating proteins to the particle surface greatly enhanced the stability of the NPs, preventing particle aggregation and improving enzymatic potency, including in vivo. Specifically, coating of collagenase I to the particle surface greatly improved the ability of the enzyme to degrade tumor collagen relative to free enzyme, thereby increasing the penetration of adjuvant chemotherapy (doxorubicin). Additionally, the protein coating reduced the rate of doxorubicin release, enabling sustained release of the small-molecule payload.
The straightforward procedure described herein permits the formulation of modular NPs that can combine and sustain the benefits of small molecules and biologics.
我们旨在提高基于蛋白质的治疗制剂的稳定性和治疗效果。
将蛋白质固定在纳米颗粒（NPs）表面，以提高蛋白质稳定性和蛋白质功能，特别是酶活性。通过在聚乳酸-乙醇酸共聚物基纳米颗粒表面包被不同分子量和功能的蛋白质，证明了该平台的模块化。
在颗粒表面包被蛋白质大大提高了纳米颗粒的稳定性，防止颗粒聚集并提高了酶活性，包括在体内。具体而言，相对于游离酶，将胶原酶I包被在颗粒表面极大地提高了该酶降解肿瘤胶原蛋白的能力，从而增加了辅助化疗（阿霉素）的渗透。此外，蛋白质包被降低了阿霉素的释放速率，实现了小分子药物的持续释放。
本文所述的简单方法允许制备模块化纳米颗粒，其可以结合并维持小分子和生物制剂的优势。
