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

JOURNAL OF CONTROLLED RELEASE

卷:320

Article

in't Veld, Ruben V. Huis¹  Ritsma, Laila²  Kleinovink, Jan Willem³  Que, Ivo¹  Ossendorp, Ferry⁴  Cruz, Luis J.¹ 

[1] Leiden Univ, Dept Radiol, Med Ctr, Leiden, Netherlands

[2] LUMC, Dept Cell & Chem Biol, Leiden, Netherlands

[3] LUMC, Dept Med Oncol, Leiden, Netherlands

[4] LUMC, Dept Immunohematol & Blood Transfus, Leiden, Netherlands

关键词: Photodynamic therapy;    Immunotherapy;    Nanoparticles;    PLGA;    Cancer;    Tumor microenvironment;    Immune modulation;    Theranostics;    Pharmacology;    Delivery;   

DOI  :  10.1016/j.jconrel.2019.12.052

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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