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Bile Acid Tethered Docetaxel‐Based Nanomicelles Mitigate Tumor Progression through Epigenetic Changes
Author(s) -
Sreekanth Vedagopuram,
Kar Animesh,
Kumar Sandeep,
Pal Sanjay,
Yadav Poonam,
Sharma Yamini,
Komalla Varsha,
Sharma Harsh,
Shyam Radhey,
Sharma Ravi Datta,
Mukhopadhyay Arnab,
Sengupta Sagar,
Dasgupta Ujjaini,
Bajaj Avinash
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202015173
Subject(s) - docetaxel , lithocholic acid , chemistry , cancer research , demethylation , pharmacology , cancer , biochemistry , bile acid , biology , medicine , gene , dna methylation , gene expression
Abstract In this study, we describe the engineering of sub‐100 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.