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

ABSTRACT: Targeted nano-delivery vehicles were developed from genetically modified Cowpea chlorotic mottle virus (CCMV) capsid by ligands bioconjugation for efficient drug delivery in cancer cells. RNA binding (N 1-25aa) and ?-hexamer forming (N 27-41aa) domain of capsid was selectively deleted by genetic engineering to achieve the efficient in vitro assembly without natural cargo. Two variants of capsids were generated by truncating 41 and 26 amino acid from N terminus (N?41 and N?26) designated as F₁ and F₂ respectively. These capsid were optimally self-assembled in 1:2 molar ratio (F₁:F₂) to form a monodisperse nano-scaffold of size 28?nm along with chemically conjugated modalities for visualization (fluorescent dye), targeting (folic acid, FA) and anticancer drug (doxorubicin). The cavity of the nano-scaffold was packed with doxorubicin conjugated gold nanoparticles (10?nm) to enhance the stability, drug loading and sustained release of drug. The chimeric system was stable at pH range of 4-8. This chimeric nano-scaffold system showed highly specific receptor mediated internalization (targeting) and ~300% more cytotoxicity (with respect to FA^- delivery system) to folate receptor positive Michigan Cancer Foundation-7 (MCF7) cell lines. The present system may offer a programmable nano-scaffold based platform for developing chemotherapeutics for cancer.

SUBMITTER: Barwal I

PROVIDER: S-EPMC5118717 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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

Barwal Indu I Kumar Rajiv R Kateriya Suneel S Dinda Amit Kumar AK Yadav Subhash Chandra SC

Scientific reports 20161122

Targeted nano-delivery vehicles were developed from genetically modified Cowpea chlorotic mottle virus (CCMV) capsid by ligands bioconjugation for efficient drug delivery in cancer cells. RNA binding (N 1-25aa) and β-hexamer forming (N 27-41aa) domain of capsid was selectively deleted by genetic engineering to achieve the efficient in vitro assembly without natural cargo. Two variants of capsids were generated by truncating 41 and 26 amino acid from N terminus (NΔ41 and NΔ26) designated as F<sub ...[more]

PMID: 27872483

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Project description:Biological nanoparticles, such as exosomes, offer an approach to drug delivery because of their innate ability to transport biomolecules. Exosomes are derived from cells and an integral component of cellular communication. However, the cellular cargo of human exosomes could negatively impact their use as a safe drug carrier. Additionally, exosomes have the intrinsic yet enigmatic, targeting characteristics of complex cellular communication. Hence, harnessing the natural transport abilities of exosomes for drug delivery requires predictably targeting these biological nanoparticles. This manuscript describes the use of two chemical modifications, incorporating a neuropilin receptor agonist peptide (iRGD) and a hypoxia-responsive lipid for targeting and release of an encapsulated drug from bovine milk exosomes to triple-negative breast cancer cells. Triple-negative breast cancer is a very aggressive and deadly form of malignancy with limited treatment options. Incorporation of both the iRGD peptide and hypoxia-responsive lipid into the lipid bilayer of bovine milk exosomes and encapsulation of the anticancer drug, doxorubicin, created the peptide targeted, hypoxia-responsive bovine milk exosomes, iDHRX. Initial studies confirmed the presence of iRGD peptide and the exosomes' ability to target the αvβ3 integrin, overexpressed on triple-negative breast cancer cells' surface. These modified exosomes were stable under normoxic conditions but fragmented in the reducing microenvironment created by 10 mM glutathione. In vitro cellular internalization studies in monolayer and three-dimensional (3D) spheroids of triple-negative breast cancer cells confirmed the cell-killing ability of iDHRX. Cell viability of 50% was reached at 10 μM iDHRX in the 3D spheroid models using four different triple-negative breast cancer cell lines. Overall, the tumor penetrating, hypoxia-responsive exosomes encapsulating doxorubicin would be effective in reducing triple-negative breast cancer cells' survival.

Dataset Information

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

Publications

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

Similar Datasets

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