NIR Fluorescent Imaging and Photodynamic Therapy with a Novel Theranostic Phospholipid Probe for Triple-Negative Breast Cancer Cells.

Abstract

New exogenous probes are needed for both imaging diagnostics and therapeutics. Here, we introduce a novel nanocomposite near-infrared (NIR) fluorescent imaging probe and test its potency as a photosensitizing agent for photodynamic therapy (PDT) against triple-negative breast cancer cells. The active component in the nanocomposite is a small molecule, pyropheophorbide a-phosphatidylethanolamine-QSY21 (Pyro-PtdEtn-QSY), which is imbedded into lipid nanoparticles for transport in the body. The probe targets abnormal choline metabolism in cancer cells; specifically, the overexpression of phosphatidylcholine-specific phospholipase C (PC-PLC) in breast, prostate, and ovarian cancers. Pyro-PtdEtn-QSY consists of a NIR fluorophore and a quencher, attached to a PtdEtn moiety. It is selectively activated by PC-PLC resulting in enhanced fluorescence in cancer cells compared to normal cells. In our in vitro investigation, four breast cancer cell lines showed higher probe activation levels than noncancerous control cells, immortalized human mammary gland cells, and normal human T cells. Moreover, the ability of this nanocomposite to function as a sensitizer in PDT experiments on MDA-MB-231 cells suggests that the probe is promising as a theranostic agent.

• Authors: Natalia I Rubtsova, Michael C Hart, Alejandro D Arroyo, Sofya A Osharovich, Benjamin K Liebov, Joann Miller, Min Yuan, Jeffrey M Cochran, Sanghoon Chong, Arjun G Yodh, Theresa M Busch, E James Delikatny, Nadia Anikeeva, Anatoliy V Popov
• Journal: Bioconjugate chemistry (Bioconjug Chem) Vol. 32 Issue 8 Pg. 1852-1863 (08 18 2021) ISSN: 1520-4812 [Electronic] United States
• PMID: 34139845 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Lipids
• Phospholipids

Topics

• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Drug Design
• Humans
• Lipids (chemistry, pharmacology)
• Molecular Structure
• Nanoparticles (chemistry)
• Phospholipids (chemistry, pharmacology)
• Photochemotherapy
• Spectrophotometry, Infrared
• Triple Negative Breast Neoplasms (therapy)