Title

Leutusome: A Biomimetic Nanoplatform Integrating Plasma Membrane Components of Leukocytes and Tumor Cells for Remarkably Enhanced Solid Tumor Homing

Abstract

Cell membrane-camouflaged nanoparticles have appeared as a promising platform to develop active tumor targeting nanomedicines. To evade the immune surveillance, we designed a composite cell membrane-camouflaged biomimetic nanoplatform, namely, leutusome, which is made of liposomal nanoparticles incorporating plasma membrane components derived from both leukocytes (murine J774A.1 cells) and tumor cells (head and neck tumor cells HN12). Exogenous phospholipids were used as building blocks to fuse with two cell membranes to form liposomal nanoparticles. Liposomal nanoparticles made of exogenous phospholipids only or in combination with one type of cell membrane were fabricated and compared. The anticancer drug paclitaxel (PTX) was used to make drug-encapsulating liposomal nanoparticles. Leutusome resembling characteristic plasma membrane components of the two cell membranes were examined and confirmed in vitro. A xenograft mouse model of head and neck cancer was used to profile the blood clearance kinetics, biodistribution, and antitumor efficacy of the different liposomal nanoparticles. The results demonstrated that leutusome obtained prolonged blood circulation and was most efficient accumulating at the tumor site (79.1 ± 6.6% ID per gram of tumor). Similarly, leutusome composed of membrane fractions of B16 melanoma cells and leukocytes (J774A.1) showed prominent accumulation within the B16 tumor, suggesting the generalization of the approach. Furthermore, PTX-encapsulating leutusome was found to most potently inhibit tumor growth while not causing systemic adverse effects.

Department(s)

Chemical and Biochemical Engineering

Comments

This work was supported, in part, by the National Science Foundation (CAREER Award CBET0954957) (to H.Y.), VCU’s CTSA (UL1TR000058 from the National Institutes of Health’s National Center for Advancing Translational Science) and the Center for Clinical and Translational Research (CCTR) Endowment Fund of the Virginia Commonwealth University (to H.Y. and S.G.) as well as VA MERIT award (IO1 BX002297) (to S.G.).

Keywords and Phrases

Active targeting; cell membrane camouflage; leukocytes; nanoparticles; tumor cells; tumor microenvironment

International Standard Serial Number (ISSN)

1530-6984; 1530-6992

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2018 American Chemical Society (ACS), All rights reserved.

Publication Date

10 Oct 2018

PubMed ID

30207473

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