Near-Infrared Fluorescent Macromolecular Reporters for Real-Time Imaging and Urinalysis of Cancer Immunotherapy.
J Am Chem Soc
; 142(15): 7075-7082, 2020 04 15.
Article
em En
| MEDLINE
| ID: mdl-32196318
ABSTRACT
Real-time imaging of immunoactivation is imperative for cancer immunotherapy and drug discovery; however, most existing imaging agents possess "always-on" signals and thus have poor signal correlation with immune responses. Herein, renal-clearable near-infrared (NIR) fluorescent macromolecular reporters are synthesized to specifically detect an immunoactivation-related biomarker (granzyme B) for real-time evaluation of cancer immunotherapy. Composed of a peptide-caged NIR signaling moiety linked with a hydrophilic poly(ethylene glycol) (PEG) passivation chain, the reporters not only specifically activate their fluorescence by granzyme B but also passively target the tumor of living mice after systemic administration. Such granzyme B induced in vivo signals of the reporters are validated to correlate well with the populations of cytotoxic T lymphocytes (CD8+) and T helper (CD4+) cells detected in tumor tissues. By virtue of their ideal renal clearance efficiency (60% injected doses at 24 h postinjection), the reporters can be used for optical urinalysis of immunoactivation simply by detecting the status of excreted reporters. This study thus proposes a molecular optical imaging approach for noninvasive evaluation of cancer immunotherapeutic efficacy in living animals.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Urinálise
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Espectroscopia de Luz Próxima ao Infravermelho
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Imagem Óptica
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Imunoterapia
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Neoplasias
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article