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Targeting Myeloid-Derived Suppressor Cells via Dual-Antibody Fluorescent Nanodiamond Conjugate
Colin D Angell1, Gabriella Lapurga1, Steven H Sun1,2
1The Arthur G. James Comprehensive Cancer Center and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
Abstract:
Fluorescent nanodiamonds (FNDs) are carbon-based nanomaterials that emit bright, photostable fluorescence and exhibit a modifiable surface chemistry. Myeloid-derived suppressor cells (MDSCs) are an immunosuppressive cell population known to expand in cancer patients and contribute to worse patient outcomes. To target MDSC, glycidol-coated FND were conjugated with antibodies against the murine MDSC markers, CD11b and GR1 (dual-Ab FND). In vitro, dual-Ab FND uptake by murine MDSC was significantly higher than IgG-coated FND (94.7% vs. 69.0%, p < 0.05). In vivo, intra-tumorally injected dual-Ab FND primarily localized to the tumor 2 and 24 h post-injection, as measured by in vivo fluorescence imaging and flow cytometry analysis of the spleen and tumor. Dual-Ab FND were preferentially taken up by intra-tumoral MDSC, representing 87.1% and 83.0% of FND+ cells in the tumor 2 and 24 h post-injection, respectively. Treatment of mice with anti-PD-L1 immunotherapy prior to intra-tumoral injection of dual-Ab FND did not significantly alter the uptake of FND by MDSC. These results demonstrate the ability of our novel dual-antibody conjugated FND to target MDSC and reveal a potential strategy for targeted delivery to other specific immune cell populations in future cancer research.
Insights
Novel fluorescent nanodiamonds (FNDs) conjugated with antibodies effectively target myeloid-derived suppressor cells (MDSCs). This targeted delivery strategy shows promise for cancer research and immunotherapy applications.
Area of Science:
- Nanotechnology
- Immunology
- Cancer Research
Background:
- Fluorescent nanodiamonds (FNDs) offer bright, photostable fluorescence and tunable surface chemistry.
- Myeloid-derived suppressor cells (MDSCs) are immunosuppressive cells that expand in cancer patients, correlating with poor outcomes.
Purpose of the Study:
- To develop and evaluate dual-antibody conjugated FNDs for targeted delivery to murine MDSCs.
- To assess the in vitro and in vivo targeting efficiency of these FNDs in a tumor model.
Main Methods:
- Glycidol-coated FNDs were conjugated with antibodies against murine MDSC markers CD11b and GR1 (dual-Ab FND).
- In vitro FND uptake by MDSCs was compared between dual-Ab FND and IgG-coated FND.
- In vivo biodistribution and tumor localization of dual-Ab FND were assessed using fluorescence imaging and flow cytometry.
- MDSC uptake of dual-Ab FND in tumors was quantified post-injection, with and without anti-PD-L1 immunotherapy.
Main Results:
- Dual-Ab FND showed significantly higher in vitro uptake by murine MDSCs compared to control FND (94.7% vs. 69.0%).
- In vivo, dual-Ab FND primarily localized to tumors post-injection and were preferentially taken up by intra-tumoral MDSCs (87.1% and 83.0% at 2 and 24h).
- Pre-treatment with anti-PD-L1 immunotherapy did not significantly affect FND uptake by MDSCs.
Conclusions:
- Novel dual-antibody conjugated FNDs demonstrate effective targeting of MDSCs.
- This approach represents a potential strategy for targeted delivery of therapeutics or imaging agents to MDSCs in cancer research.
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