Photodynamic cancer therapy enhances accumulation of nanoparticles in tumor-associated myeloid cells.

Autor: Huis In 't Veld RV; Department of Radiology, Leiden University Medical Centre (LUMC), the Netherlands., Ritsma L; Department of Cell and Chemical Biology, LUMC, Leiden, the Netherlands., Kleinovink JW; Department of Medical Oncology, LUMC, Leiden, the Netherlands., Que I; Department of Radiology, Leiden University Medical Centre (LUMC), the Netherlands., Ossendorp F; Department of Immunohematology and Blood Transfusion, LUMC, Leiden, the Netherlands., Cruz LJ; Department of Radiology, Leiden University Medical Centre (LUMC), the Netherlands. Electronic address: l.j.cruz_ricondo@lumc.nl.
Jazyk: angličtina
Zdroj: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2020 Apr 10; Vol. 320, pp. 19-31. Date of Electronic Publication: 2019 Dec 31.
DOI: 10.1016/j.jconrel.2019.12.052
Abstrakt: In cancer treatment, nanomedicines may be employed in an attempt to improve the tumor localization of antineoplastic drugs e.g. immunotherapeutic agents either through passive or active targeting, thereby potentially enhancing therapeutic effect and reducing undesired off-target effects. However, a large number of administrated nanocarriers often fail to reach the tumor area. In the present study, we show that photodynamic therapy (PDT) enhances the tumor accumulation of systemically administered lipid-PEG layer coated poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NP). Intravital microscopy and histological analysis of the tumor area reveal that the tumor vasculature was disrupted after PDT, disturbing blood flow and coinciding with entrapment of nanocarriers in the tumor area. We observed that the nanoparticles accumulating after treatment do not confine to specific locations within the tumor, but rather localize to various cells present throughout the tumor area. Finally, we show by flow cytometry that NP accumulation occurred mostly in immune cells of the myeloid lineage present in the tumor microenvironment (TME) as well as in tumor cells, albeit to a lower extent. These data expose opportunities for combination treatments of clinical PDT with NP-based immunotherapy to modulate the TME and improve antitumor immune responses.
Competing Interests: Declaration of Competing Interest The authors were supported with funding from Leiden University Medical Center and the Netherlands Organization for Scientific Research (NWO). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in, or financial conflict with, the subject matter or materials discussed in the manuscript, apart from those already disclosed.
(Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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