Photosensitization Priming of Tumor Microenvironments Improves Delivery of Nanotherapeutics via Neutrophil Infiltration

Remodeling of tumor microenvironments enables enhanced delivery of nanoparticles (NPs). This study shows that direct priming of a tumor tissue using photosensitization rapidly activates neutrophil infiltration that mediates delivery of nanotherapeutics into the tumor. A drug delivery platform is com...

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Bibliographic Details
Published in:Advanced materials (Weinheim) 2017-07, Vol.29 (27), p.n/a
Main Authors: Chu, Dafeng, Dong, Xinyue, Zhao, Qi, Gu, Jingkai, Wang, Zhenjia
Format: Article
Language:English
Subjects:
Animals
Antibodies
Cancer
Cancer therapies
cancer therapy
Drug delivery systems
Gold
Infiltration
Materials science
Mice
nanoparticle drug delivery
Nanoparticles
Nanorods
nanotherapeutics
Neutrophil Infiltration
Neutrophils
Photosensitivity Disorders
Priming
Rodents
Therapy
Tumor Microenvironment
tumor microenvironments
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Summary:Remodeling of tumor microenvironments enables enhanced delivery of nanoparticles (NPs). This study shows that direct priming of a tumor tissue using photosensitization rapidly activates neutrophil infiltration that mediates delivery of nanotherapeutics into the tumor. A drug delivery platform is comprised of NPs coated with anti‐CD11b antibodies (Abs) that target activated neutrophils. Intravital microscopy demonstrates that the movement of anti‐CD11b Abs‐decorated NPs (NPs‐CD11b) into the tumor is mediated by neutrophil infiltration induced by photosensitization (PS) because the systemic depletion of neutrophils completely abolishes the nanoparticle tumor deposition. The neutrophil uptake of NPs does not alter neutrophil activation and transmigration. For cancer therapy in mice, tumor PS and photothermal therapy of anti‐CD11b Abs‐linked gold nanorods (GNRs‐CD11b) are combined to treat the carcinoma tumor. The result indicates that neutrophil tumor infiltration enhances nanoparticle cancer therapy. The findings reveal that promoting tumor infiltration of neutrophils by manipulating tumor microenvironments could be a novel strategy to actively deliver nanotherapeutics in cancer therapies. Active delivery of nanotherapeutics to tumors is mediated by neutrophil infiltration after the tumor is photosensitized to induce acute inflammation. Anti‐CD11b antibody‐decorated nanoparticles are specifically internalized by activated neutrophils in vivo that mediate the tumor deposition of NPs. Photothermal therapy using this approach dramatically improves the cancer treatment in mice.
ISSN:0935-9648
1521-4095
DOI:10.1002/adma.201701021