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Nano-Differential Scanning Fluorimetry for Screening in Fragment-based Lead Discovery
Published on: May 16, 2021
A quantitative method for screening and identifying molecular targets for nanomedicine
Peng Guo1, Jiang Yang2, Diane R Bielenberg2
1Department 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.
Researchers developed a quantitative method to find new molecular targets for cancer nanomedicine. This approach identified ICAM-1 as a promising target for metastatic melanoma, improving drug delivery and reducing tumor growth.
Area of Science:
- Biomedical Engineering
- Oncology
- Nanotechnology
Background:
- Current cancer nanomedicines often lack tumor specificity, leading to off-target toxicity and limited efficacy.
- Identifying reliable molecular targets is crucial for developing effective tumor-targeted nanomedicine.
- Metastatic melanoma (MM) presents challenges in targeted therapy due to its heterogeneity and spread.
Purpose of the Study:
- To establish a quantitative screening method for identifying novel molecular targets for tumor-targeted nanomedicine.
- To evaluate Intercellular Adhesion Molecule-1 (ICAM-1) as a potential molecular target for metastatic melanoma nanomedicine.
- To develop and assess antibody-functionalized nanocarriers for targeted drug delivery and simultaneous target neutralization.
Main Methods:
- Comparative flow cytometry was employed for high-throughput screening of potential targets.
- ICAM-1 expression was quantified on cells and validated using immunohistochemistry on human tissue specimens.
- Doxorubicin-encapsulating immunoliposomes conjugated with anti-ICAM-1 antibodies (ICAM-Dox-LPs) were engineered and characterized.
Main Results:
- ICAM-1 was identified as a specific and highly expressed target on metastatic melanoma cells.
- ICAM-Dox-LPs demonstrated selective binding, internalization, and doxorubicin delivery to MM cells.
- Simultaneous inhibition of MM cell proliferation and migration was achieved through ICAM-1 blockade and doxorubicin delivery.
Conclusions:
- A novel quantitative metric system effectively identifies and evaluates molecular targets for cancer nanomedicine.
- ICAM-1 is a promising target for developing targeted nanomedicines against metastatic melanoma.
- Functionalized immunoliposomes offer a dual therapeutic strategy for enhanced anti-cancer effects.

