Related Experiment Video
Updated: Mar 5, 2026
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.
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.
Insights
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.
