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

Abstract

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.

Cabozantinib unlocks efficient in vivo targeted delivery of neutrophil-loaded nanoparticles into murine prostate tumors

“…To maximize the potential clinical translation of this technology, it may also be possible to optimize this targeted approach by altering the BSA-coatingfor example, by using denatured BSA rather than native BSA used in this study, and screening for additional tyrosine kinase inhibitors or precision medicine therapies which promote neutrophil activation and infiltration. Greater neutrophil infiltration has been associated with improved survival in early stage lung cancer and gastric cancer (24)(25)(26), highlighting the broad applicability of a neutrophil-mediated targeted NP delivery strategy in oncology.…”

The interplay between neutrophils and microbiota in cancer

“…Advances in intravital microscopy and real‐time in vitro imaging of neutrophils will also contribute to the study of neutrophil functions in cancer progression and therapy. Already, many neutrophil‐targeting therapies are being explored to prevent neutrophil reprograming, block neutrophil migration to the tumor or take advantage of their migration to deliver anti‐cancer drugs . The therapeutic gain that could be achieved from a better understanding of the microbiota‐neutrophil‐cancer axis has the potential to be truly beneficial for a very heterogeneous disease such as cancer.…”

Targeting Inflammatory Vasculature by Extracellular Vesicles

“…In nanomedicine, drug delivery using nanoparticles (NPs) improves therapies for a wide range of diseases since NPs can efficiently carry and deliver drugs (2–6). For example, synthetic NPs made from lipids (7), polymers (8), proteins (9–11) and metals (12, 13) have been shown to have many applications in drug delivery. Compared to free drugs, drug-loaded nanoparticles possess several advantages, such as improved drug solubility, targeting ability, and longer circulation times (6, 14).…”