Multifunctional and degradable zwitterionic nanogels for targeted delivery, enhanced MR imaging, reduction-sensitive drug release, and renal clearance

• Published in: Biomaterials 2011-07, Vol.32 (20), p.4604-4608
• Main Authors: Zhang, Lei, Xue, Hong, Cao, Zhiqiang, Keefe, Andrew, Wang, Jinnan, Jiang, Shaoyi
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Animals; Biocompatible Materials - chemistry; Biocompatible Materials - metabolism; Cell Line; Degradable; Dentistry; Dextrans - chemistry; Dextrans - metabolism; Drug Carriers - chemistry; Drug Carriers - metabolism; Drug Delivery Systems; Endothelial Cells - cytology; Endothelial Cells - metabolism; Gels - chemistry; Gels - metabolism; Humans; Kidney - metabolism; Kidney Function Tests; Macrophages - cytology; Macrophages - metabolism; Magnetic Resonance Imaging - methods; Materials Testing; Mice; MRI (magnetic resonance imaging); Nanoparticles - chemistry; Reduction-sensitive; Renal clearance; Targeting; Zwitterionic
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2011.02.064

Abstract Multifunctional and degradable nanogels encapsulating both model drug (fluorescently labeled dextran) and imaging reagent (monodisperse Fe3 O4 nanoparticles) were developed by polymerizing zwitterionic monomers with a disulfide crosslinker. Results show that the nanogels have a hydrodynamic size of about 110 nm in saline solution and their size remained unchanged for over 6 months. After being conjugated with a targeting ligand, the nanogels showed a significant cellular uptake by human umbilical vein endothelial cells (HUVEC). The nanogels show low macrophage uptake, implying potential low interaction with the innate immune system. Upon entering the reducing intracellular environment, the disulfide bonds were efficiently cleaved, resulting in the spontaneous release of the encapsulated model drug and Fe3 O4 nanoparticles. Magnetic resonance imaging (MRI) studies show that the encapsulation of multiple monodisperse Fe3 O4 nanoparticles by the nanogels significantly enhanced their MRI performance (R2 relaxivity), while the disassembling of the Fe3 O4 nanoparticles due to the nanogels degradation brings their R2 relaxivity back to that of their original monodisperse form. Furthermore, the degradation properties enable the removal of the disassembled nanogels from the body by renal clearance.