磁共振成像
电穿孔
生物标志物
癌症研究
免疫系统
树突状细胞
医学
免疫学
化学
放射科
生物化学
基因
作者
Adam Grippin,Brandon Wummer,Tyler J. Wildes,Kyle Dyson,Vrunda Trivedi,Changlin Yang,Mathew Sebastian,Héctor R. Méndez‐Gómez,Suraj Padala,Mackenzie Grubb,Matthew G. Fillingim,Adam Monsalve,Elias Sayour,Jon Dobson,Duane A. Mitchell
出处
期刊:ACS Nano
[American Chemical Society]
日期:2019-11-15
卷期号:13 (12): 13884-13898
被引量:83
标识
DOI:10.1021/acsnano.9b05037
摘要
Cancer vaccines initiate antitumor responses in a subset of patients, but the lack of clinically meaningful biomarkers to predict treatment response limits their development. Here, we design multifunctional RNA-loaded magnetic liposomes to initiate potent antitumor immunity and function as an early biomarker of treatment response. These particles activate dendritic cells (DCs) more effectively than electroporation, leading to superior inhibition of tumor growth in treatment models. Inclusion of iron oxide enhances DC transfection and enables tracking of DC migration with magnetic resonance imaging (MRI). We show that T2*-weighted MRI intensity in lymph nodes is a strong correlation of DC trafficking and is an early predictor of antitumor response. In preclinical tumor models, MRI-predicted "responders" identified 2 days after vaccination had significantly smaller tumors 2–5 weeks after treatment and lived 73% longer than MRI-predicted "nonresponders". These studies therefore provide a simple, scalable nanoparticle formulation to generate robust antitumor immune responses and predict individual treatment outcome with MRI.
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