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Multi-Walled Carbon Nanotubes Decorated with Guanidinylated Dendritic Molecular Transporters: An Efficient Platform for the Selective Anticancer Activity of Doxorubicin

Abstract

An efficient doxorubicin (DOX) drug delivery system with specificity against tumor cells was developed, based on multi-walled carbon nanotubes (MWCNTs) functionalized with guanidinylated dendritic molecular transporters. Acid-treated MWCNTs (oxCNTs) interacted both electrostatically and through hydrogen bonding and van der Waals attraction forces with guanidinylated derivatives of 5000 and 25,000 Da molecular weight hyperbranched polyethyleneimine (GPEI5K and GPEI25K). Chemical characterization of these GPEI-functionalized oxCNTs revealed successful decoration with GPEIs all over the oxCNTs sidewalls, which, due to the presence of guanidinium groups, gave them aqueous compatibility and, thus, exceptional colloidal stability. These GPEI-functionalized CNTs were subsequently loaded with DOX for selective anticancer activity, yielding systems of high DOX loading, up to 99.5% encapsulation efficiency, while the DOX-loaded systems exhibited pH-triggered release and higher therapeutic efficacy compared to that of free DOX. Most importantly, the [email protected] system caused high and selective toxicity against cancer cells in a non-apoptotic, fast and catastrophic manner that cancer cells cannot recover from. Therefore, the [email protected] nanocarrier was found to be a potent and efficient nanoscale DOX delivery system, exhibiting high selectivity against cancerous cells, thus constituting a promising candidate for cancer therapy.

Funding source: EU under the FP7 PEOPLE-2012-IAPP-SANAD project (No 324443) and the internal project entitled: “Synthesis and characterization of nanostructured materials for environmental applications” (EE11968); “National Infrastructure in Nanotechnology, Advanced Materials; Micro-/Nanoelectronics” INNOVATION-EL (MIS 5002772) and “A Greek Research Infrastructure for Visualizing and Monitoring Fundamental Biological Processes (BioImagingGR)” (MIS 5002755), which are implemented under the Action “Reinforcement of the Research and Innovation Infrastructure”, funded by the Operational Program “Competitiveness, Entrepreneurship, and Innovation” (NSRF 2014–2020) Greece and the European Union (European Regional Development Fund) Greek State Scholarships Foundation, program “Enhancement of human scientific resources through implementation of PhD research”; European program “Development of human resources, Education and lifelong learning”, 2014–2020, co-funded by the European Social Fund and Greek State (MIS 5000432).
Related subjects: Applications & Pathways
Countries: Greece
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2021-06-09
2021-07-24
http://instance.metastore.ingenta.com/content/journal2178
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