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Targeted delivery system for cancer cells consist of multiple ligands conjugated genetically modified CCMV capsid on

Indu Barwal1,2, Rajiv Kumar3, Suneel Kateriya4

  • 1TERI University, Vasant Kunj, New Delhi, 110070, India.

Scientific Reports
|November 23, 2016
PubMed

Insights

Genetically engineered Cowpea chlorotic mottle virus (CCMV) capsids form targeted nano-scaffolds for cancer drug delivery. These novel nanocarriers demonstrate enhanced cytotoxicity against folate receptor-positive cancer cells.

Area of Science:

  • Biotechnology
  • Nanomedicine
  • Virology

Background:

  • Cowpea chlorotic mottle virus (CCMV) capsids offer a robust platform for nanocarrier development.
  • Genetic engineering allows modification of CCMV capsid structure for specific applications.
  • Targeted drug delivery systems are crucial for improving cancer therapy efficacy.

Purpose of the Study:

  • To engineer CCMV capsids into targeted nano-delivery vehicles for enhanced anticancer drug delivery.
  • To create a self-assembled, monodisperse nano-scaffold capable of carrying therapeutic payloads.
  • To evaluate the specificity and efficacy of the developed nano-scaffold in folate receptor-positive cancer cells.

Main Methods:

  • Selective deletion of RNA binding and β-hexamer forming domains of CCMV capsid via genetic engineering.
  • In vitro self-assembly of two engineered capsid variants (NΔ41 and NΔ26) into a nano-scaffold.
  • Chemical conjugation of targeting ligands (folic acid), visualization dyes, and doxorubicin-loaded gold nanoparticles.
  • Assessment of nano-scaffold stability, cellular uptake, and cytotoxicity in MCF7 cancer cell lines.

Main Results:

  • Successfully generated two CCMV capsid variants (F1 and F2) and assembled them into a 28 nm monodisperse nano-scaffold.
  • The nano-scaffold was loaded with doxorubicin-conjugated gold nanoparticles, enhancing drug stability, loading, and sustained release.
  • The chimeric nano-scaffold demonstrated pH stability between 4-8 and exhibited highly specific, receptor-mediated internalization.
  • A ~300% increase in cytotoxicity was observed in folate receptor-positive MCF7 cells compared to non-targeted systems.

Conclusions:

  • Engineered CCMV capsids provide a versatile platform for creating targeted nano-scaffolds for cancer therapy.
  • The developed nano-scaffold system shows significant potential for improving the delivery and efficacy of chemotherapeutics.
  • This programmable nanocarrier platform may lead to the development of advanced cancer treatment strategies.

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