Bile Acid Tethered Docetaxel-Based Nanomicelles Mitigate Tumor Progression through Epigenetic Changes.
Angew Chem Int Ed Engl
; 60(10): 5394-5399, 2021 03 01.
Article
en En
| MEDLINE
| ID: mdl-33258265
ABSTRACT
In this study, we describe the engineering of sub-100â
nm nanomicelles (DTX-PC NMs) derived from phosphocholine derivative of docetaxel (DTX)-conjugated lithocholic acid (DTX-PC) and poly(ethylene glycol)-tethered lithocholic acid. Administration of DTX-PC NMs decelerate tumor progression and increase the mice survivability compared to Taxotere (DTX-TS), the FDA-approved formulation of DTX. Unlike DTX-TS, DTX-PC NMs do not cause any systemic toxicity and slow the decay rate of plasma DTX concentration in rodents and non-rodent species including non-human primates. We further demonstrate that DTX-PC NMs target demethylation of CpG islands of Sparcl1 (a tumor suppressor gene) by suppressing DNA methyltransferase activity and increase the expression of Sparcl1 that leads to tumor regression. Therefore, this unique system has the potential to improve the quality of life in cancer patients and can be translated as a next-generation chemotherapeutic.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Epigénesis Genética
/
Docetaxel
/
Ácido Litocólico
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Neoplasias
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Antineoplásicos
Aspecto:
Patient_preference
Límite:
Animals
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Año:
2021
Tipo del documento:
Article
País de afiliación:
India