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J Control Release. 2017 Oct 10;263:57-67. doi: 10.1016/j.jconrel.2017.03.030. Epub 2017 Mar 22.

A quantitative method for screening and identifying molecular targets for nanomedicine.

Author information

1
Department of Biomedical Engineering, The City College of New York, 160 Convent Avenue, New York, NY 10031, United States; Vascular Biology Program, Boston Children's Hospital, 1 Blackfan Circle, Boston, MA 02115, United States; Department of Surgery, Harvard Medical School, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, United States.
2
Vascular Biology Program, Boston Children's Hospital, 1 Blackfan Circle, Boston, MA 02115, United States; Department of Surgery, Harvard Medical School, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, United States.
3
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, United States.
4
Department of Anesthesia, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, United States.
5
Department of Biomedical Engineering, The City College of New York, 160 Convent Avenue, New York, NY 10031, United States. Electronic address: dauguste@ccny.cuny.edu.

Abstract

Identifying a molecular target is essential for tumor-targeted nanomedicine. Current cancer nanomedicines commonly suffer from poor tumor specificity, "off-target" toxicity, and limited clinical efficacy. Here, we report a method to screen and identify new molecular targets for tumor-targeted nanomedicine based on a quantitative analysis. In our proof-of-principle study, we used comparative flow cytometric screening to identify ICAM-1 as a potential target for metastatic melanoma (MM). We further evaluated ICAM-1 as a MM targeting moiety by characterizing its (1) tumor specificity, (2) expression level, (3) cellular internalization, (4) therapeutic function, and (5) potential clinical impact. Quantitation of ICAM-1 protein expression on cells and validation by immunohistochemistry on human tissue specimens justified the synthesis of antibody-functionalized drug delivery vehicles, which were benchmarked against appropriate controls. We engineered ICAM-1 antibody conjugated, doxorubicin encapsulating immunoliposomes (ICAM-Dox-LPs) to selectively recognize and deliver doxorubicin to MM cells and simultaneously neutralize ICAM-1 signaling via an antibody blockade, demonstrating significant and simultaneous inhibitory effects on MM cell proliferation and migration. This paper describes a novel, quantitative metric system that identifies and evaluates new cancer targets for tumor-targeting nanomedicine.

KEYWORDS:

Cancer target; Drug delivery; ICAM-1; Immunoliposome; Metastatic melanoma; Nanomedicine

PMID:
28341549
PMCID:
PMC5603366
DOI:
10.1016/j.jconrel.2017.03.030
[Indexed for MEDLINE]
Free PMC Article

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