Journal
ACS NANO
Volume 13, Issue 12, Pages 13884-13898Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.9b05037
Keywords
iron oxide; dendritic cells; cancer immunotherapy; biomarker; liposome; RNA; RNA-lipoplex; vaccine; nanoparticle; cancer
Categories
Funding
- Circle of Hope Foundation
- University of Florida Health Cancer Center Dissertation Award
- NIH/NCI [1R01CA175517, R01CA195563, K08CA199224, TL1TR001428, 1F30CA228280-01]
- National Science Foundation [DMR-1157490, DMR-1644779]
- State of Florida
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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 T-2*-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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