Self-Reporting Molecular Prodrug for In Situ Quantitative Sensing of Drug Release by Ratiometric Photoacoustic Imaging.
ACS Sens
; 8(12): 4737-4746, 2023 Dec 22.
Article
em En
| MEDLINE
| ID: mdl-38008917
ABSTRACT
Understanding the pharmacokinetics of prodrugs in vivo necessitates quantitative, noninvasive, and real-time monitoring of drug release, despite its difficulty. Ratiometric photoacoustic (PA) imaging, a promising deep tissue imaging technology with a unique capacity for self-calibration, can aid in solving this problem. Here, for the first time, a methylamino-substituted Aza-BODIPY (BDP-N) and the chemotherapeutic drug camptothecin (CPT) are joined via a disulfide chain to produce the molecular theranostic prodrug (BSC) for real-time tumor mapping and quantitative visualization of intratumoral drug release using ratiometric PA imaging. Intact BSC has an extremely low toxicity, with a maximum absorption at â¼720 nm; however, endogenous glutathione (GSH), which is overexpressed in tumors, will cleave the disulfide bond and liberate CPT (with full toxicity) and BDP-N. This is accompanied by a significant redshift in absorption at â¼800 nm, resulting in the PA800/PA720 ratio. In vitro, a linear relationship is successfully established between PA800/PA720 values and CPT release rates, and subsequent experiments demonstrate that this relationship can also be applied to the quantitative detection of intratumoral CPT release in vivo. Notably, the novel ratiometric strategy eliminates nonresponsive interference and amplifies the multiples of the signal response to significantly improve the imaging contrast and detection precision. Therefore, this research offers a viable alternative for the design of molecular theranostic agents for the clinical diagnosis and treatment of tumors.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pró-Fármacos
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Nanopartículas
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Técnicas Fotoacústicas
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Neoplasias
Limite:
Humans
Idioma:
En
Revista:
ACS Sens
Ano de publicação:
2023
Tipo de documento:
Article