Lei Zou, Youhua Tao, Gregory Payne, Tima Thomas and Huanyu Dou
Department of Biomedical Sciences, Paul L. Foster School of Medicine,USA
Biomedical Sciences graduate School, Texas Tech University Health Sciences Center, USA
Posters & Accepted Abstracts: Immunotherapy (Los Angel)
Nanotechnology and convection-enhanced delivery have been developed in recent years for treatment of glioma, each with highly desirable strengths in certain aspects, but limitations in other aspects. The development of an effective brainglioma targeting delivery system for glioma therapy is much needed. We developed a novel drug carrier that can combine the advantages of both liposomes and polymeric NPs to target brain-tumor associated macrophages (TAMs). By phagocytosis, the innate immune TAMs can take up NPs to initiate anti-glioma immune responses and transport drugs to destroy neighboring tumor cells. Nanoparticles (NPs) containing mixed lipid monolayer shell, biodegradable polymer core were conjugated with rabies virus glycoprotein (RVG) peptide as brain targeting ligand. Anti-glioma drug, paclitaxel (PTX), was loaded to RVG-NPs to treat malignant glioma. Characterization by AFM, nanosizer and HPLC assays showed that the size-controlled RVG-PTXNPs had the desirable size (~140 nm), narrow size distribution and spherical shape. With a size of 140 nm, RVG-PTX-NPs prevented uptake by neurons and selective targeting to the brain TAMs with controlled release and tumor specific toxicity. In vivo studies revealed that RVG-PTX-NPs were able to cross the blood-brain barrier (BBB) and had specific targeting to the brain. Most importantly, RVG-PTX-NPs showed effectiveness as anti-glioma therapy on mice model for human glioma. We concluded that RVG-PTX-NPs provided an effective approach for brain-TAMs targeted delivery for the treatment of glioma.
Email: hunyu.dou@ttuhsc.edu
