Protease-Responsive Targeted Delivery of Doxorubicin from Bilirubin-BSA-Capped Mesoporous Silica Nanoparticles against Colon Cancer

Prateek Srivastava, Sumit Kumar Hira, Divesh Narayan Srivastava, Uttam Gupta, Pradip Sen, Ram Adhar Singh, Partha Pratim Manna

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Bilirubin is regarded as a toxic waste, produced from heme degradation and also acts as a potentially important antioxidant. Bilirubin causes arrest in cell cycle and lead to lesser occurrence of malignancies in individuals, having normal or slender increase in levels of serum bilirubin. Prompted by the dynamic interaction between bilirubin and bovine serum albumin (BSA), bilirubin-BSA complex was explored as a biocompatible cap system for protease responsive delivery device of anticancer drug against colon cancer. Bilirubin, conjugated to the amine terminated and doxorubicin loaded mesoporous silica nanoparticles were employed as a novel formulation against colon carcinoma cells. Compared to doxorubicin only, bilirubin in combination with doxorubicin-loaded mesoporous silica nanoparticle significantly inhibits tumor cell growth as assessed in MC-38 (murine) and HCT-116 (human) colon cancer cells. Bilirubin-doxorubicin combination potently inhibits proliferation of tumor cells and acted as cytotoxic and pro-apoptotic agent in vitro. Our result demonstrates that this novel cap system could play a precise role in defense against colon cancer by interrupting the pro-cancerogenic survival pathways during carcinogenesis.

Original languageEnglish
Pages (from-to)3376-3385
Number of pages10
JournalACS Biomaterials Science and Engineering
Volume3
Issue number12
DOIs
StatePublished - 11 Dec 2017
Externally publishedYes

Keywords

  • apoptosis
  • bilirubin
  • colon cancer
  • doxorubicin
  • mesoporous silica

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering

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