Dual Tumor-Selective ß-Carboline-Based Fluorescent Probe for High-Contrast/Rapid Diagnosis of Clinical Tumor Tissues.
Mol Pharm
; 21(1): 152-163, 2024 Jan 01.
Article
in En
| MEDLINE
| ID: mdl-38113058
ABSTRACT
Given that precise/rapid intraoperative tumor margin identification is still challenging, novel fluorescent probes HY and HYM, based on acidic tumor microenvironment (TME) activation and organic anion transporting polypeptide (OATPs)-mediated selective uptake, were constructed and synthesized. Both of them possessed acidic pH-activatable and reversible fluorescence as well as large Stokes shift. Compared with HY, HYM had a higher (over 9-fold) enhancement in fluorescence with pH ranging from 7.6 to 4.0, and the fluorescence quantum yield of HYM (ΦF = 0.49) at pH = 4.0 was 8-fold stronger than that (ΦF = 0.06) at pH = 7.4. Mechanism research demonstrated that acidic TME-induced protonation of the pyridine N atom on ß-carbolines accounted for the pH-sensitive fluorescence by influencing the intramolecular charge transfer (ICT) effect. Furthermore, HYM selectively lit up cancer cells and tumor tissues not only by "off-on" fluorescence but also by OATPs (overexpressed on cancer cells)-mediated cancer cellular internalization, offering dual tumor selectivity for precise visualization of tumor mass and intraoperative guidance upon in situ spraying. Most importantly, HYM enabled rapid and high-contrast (tumor-to-normal tissue ratios > 6) human tumor margin identification in clinical tumor tissues by simple spraying within 6 min, being promising for aiding in clinical surgical resection.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Fluorescent Dyes
/
Neoplasms
Limits:
Humans
Language:
En
Journal:
Mol Pharm
Journal subject:
BIOLOGIA MOLECULAR
/
FARMACIA
/
FARMACOLOGIA
Year:
2024
Document type:
Article
Country of publication:
United States