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A Localized Chimeric Hydrogel Therapy Combats Tumor Progression through Alteration of Sphingolipid Metabolism.

Rapid proliferation of cancer cells assisted by endothelial cell-mediated angiogenesis and acquired inflammation at the tumor microenvironment (TME) lowers the success rate of chemotherapeutic regimens. Therefore, targeting these processes using localized delivery of a minimally toxic drug combinati... Full description

Journal Title: ACS central science October 23, 2019, Vol.5(10), pp.1648-1662
Main Author: Pal, Sanjay
Other Authors: Medatwal, Nihal , Kumar, Sandeep , Kar, Animesh , Komalla, Varsha , Yavvari, Prabhu Srinivas , Mishra, Deepakkumar , Rizvi, Zaigham Abbas , Nandan, Shiv , Malakar, Dipankar , Pillai, Manoj , Awasthi, Amit , Das, Prasenjit , Sharma, Ravi Datta , Srivastava, Aasheesh , Sengupta, Sagar , Dasgupta, Ujjaini , Bajaj, Avinash
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 2374-7943 ; DOI: 10.1021/acscentsci.9b00551
Link: http://search.proquest.com/docview/2310291019/?pq-origsite=primo
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title: A Localized Chimeric Hydrogel Therapy Combats Tumor Progression through Alteration of Sphingolipid Metabolism.
format: Article
creator:
  • Pal, Sanjay
  • Medatwal, Nihal
  • Kumar, Sandeep
  • Kar, Animesh
  • Komalla, Varsha
  • Yavvari, Prabhu Srinivas
  • Mishra, Deepakkumar
  • Rizvi, Zaigham Abbas
  • Nandan, Shiv
  • Malakar, Dipankar
  • Pillai, Manoj
  • Awasthi, Amit
  • Das, Prasenjit
  • Sharma, Ravi Datta
  • Srivastava, Aasheesh
  • Sengupta, Sagar
  • Dasgupta, Ujjaini
  • Bajaj, Avinash
subjects:
  • Research Article
ispartof: ACS central science, October 23, 2019, Vol.5(10), pp.1648-1662
description: Rapid proliferation of cancer cells assisted by endothelial cell-mediated angiogenesis and acquired inflammation at the tumor microenvironment (TME) lowers the success rate of chemotherapeutic regimens. Therefore, targeting these processes using localized delivery of a minimally toxic drug combination may be a promising strategy. Here, we present engineering of a biocompatible self-assembled lithocholic acid-dipeptide derived hydrogel (TRI-Gel) that can maintain sustained delivery of antiproliferating doxorubicin, antiangiogenic combretastatin-A4 and anti-inflammatory dexamethasone. Application of TRI-Gel therapy to a murine tumor model promotes enhanced apoptosis with a concurrent reduction in angiogenesis and inflammation, leading to effective abrogation of tumor proliferation and increased median survival with reduced drug resistance. In-depth RNA-sequencing analysis showed that TRI-Gel therapy induced transcriptome-wide alternative splicing of many genes responsible for oncogenic... Hydrogel-mediated delivery of antiproliferating, antiangiogenic, and anti-inflammatory drugs aid in tumor regression by altering the sphingolipid metabolism through alternative splicing.
language: eng
source:
identifier: ISSN: 2374-7943 ; DOI: 10.1021/acscentsci.9b00551
fulltext: fulltext
issn:
  • 23747943
  • 2374-7943
url: Link


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titleA Localized Chimeric Hydrogel Therapy Combats Tumor Progression through Alteration of Sphingolipid Metabolism.
creatorPal, Sanjay ; Medatwal, Nihal ; Kumar, Sandeep ; Kar, Animesh ; Komalla, Varsha ; Yavvari, Prabhu Srinivas ; Mishra, Deepakkumar ; Rizvi, Zaigham Abbas ; Nandan, Shiv ; Malakar, Dipankar ; Pillai, Manoj ; Awasthi, Amit ; Das, Prasenjit ; Sharma, Ravi Datta ; Srivastava, Aasheesh ; Sengupta, Sagar ; Dasgupta, Ujjaini ; Bajaj, Avinash
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ispartofACS central science, October 23, 2019, Vol.5(10), pp.1648-1662
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descriptionRapid proliferation of cancer cells assisted by endothelial cell-mediated angiogenesis and acquired inflammation at the tumor microenvironment (TME) lowers the success rate of chemotherapeutic regimens. Therefore, targeting these processes using localized delivery of a minimally toxic drug combination may be a promising strategy. Here, we present engineering of a biocompatible self-assembled lithocholic acid-dipeptide derived hydrogel (TRI-Gel) that can maintain sustained delivery of antiproliferating doxorubicin, antiangiogenic combretastatin-A4 and anti-inflammatory dexamethasone. Application of TRI-Gel therapy to a murine tumor model promotes enhanced apoptosis with a concurrent reduction in angiogenesis and inflammation, leading to effective abrogation of tumor proliferation and increased median survival with reduced drug resistance. In-depth RNA-sequencing analysis showed that TRI-Gel therapy induced transcriptome-wide alternative splicing of many genes responsible for oncogenic... Hydrogel-mediated delivery of antiproliferating, antiangiogenic, and anti-inflammatory drugs aid in tumor regression by altering the sphingolipid metabolism through alternative splicing.
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