鼻腔给药
医学
胶质瘤
癌症研究
药物输送
药理学
脑瘤
病理
化学
有机化学
作者
Peng Zhang,Μαρκέλλα Ζαννίκου,Maciej S. Lesniak,Irina V. Balyasnikova
出处
期刊:Neuro-oncology
[Oxford University Press]
日期:2019-11-01
卷期号:21 (Supplement_6): vi96-vi96
标识
DOI:10.1093/neuonc/noz175.398
摘要
Abstract Tumor-associated myeloid cells (TAMCs) are appealing therapeutic target in glioblastoma (GBM) due to their immunosuppressive function and robust presence in the tumor tissue. We designed a lipid nanoparticle (LNP) modified with anti-PD-L1 antibody (αPD-L1) for targeted delivery to PD-L1 expressing cells within the tumor. We demonstrate that αPD-L1-LNP are effectively and specifically taken up by TAMCs. The encapsulation of dinaciclib, an inhibitor of a cyclin-dependent kinase, into αPD-L1-LNP, leads to a robust depletion of TAMCs upon local delivery. We next investigated the therapeutic relevance of non-invasive intranasal delivery of αPD-L1-LNP drug nano formulation in a GL261 syngeneic model of glioma. We show that intranasal administration of αPD-L1-LNP/dinaciclib alone did not significantly affect the survival of tumor-bearing mice, whereas a regimen combing with fractionated irradiation led to a significantly improved animal survival of mice bearing GL261 glioma over monotherapies. Histological analysis of tissue demonstrated about a four-fold increase in the uptake of nanoparticles within the tumor bed but not in the normal brain in mice treated with fractionated irradiation over the control mice. These results warrant further development and validation of intranasal delivery of therapeutic nanoformulations targeting TAMCs in preclinical animal models to improve the outcome in GBM patients.
科研通智能强力驱动
Strongly Powered by AbleSci AI