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Development of medical-grade, discrete, multi-walled carbon nanotubes as drug delivery molecules to enhance the treatment of hematological malignancies.

ABSTRACT: Carbon nanotubes (CNTs) hold great potential as drug delivery transporters given their large drug-binding surface area. Herein, we designed novel, multi-walled, discrete CNTs (dMWCNTs), PEGylated dMWCNTs (PEG-dMWCNTs), and bone-targeting (BT), alendronate-conjugated PEG-dMWCNTs (BT-PEG-dMWCNTs). Using zeta potential, thermogravimetric analysis, TEM, SEM, and FTIR, dMWCNTs were characterized as individual, uniform, and stable. Drug binding and release assays validated dMWCNTs as effective doxorubicin (DOX) transporters. The mass ratio of DOX loading onto dMWCNTs was 35% wt/wt with a ~95% wt/wt efficiency. DOX release was ~51% w/w after 48 hours. Neoplastic transformation, chromosomal aberration, and cytotoxicity assays, confirmed biocompatibility for all dMWCNTs. PEG-dMWCNTs were well tolerated and modulated drug pharmacokinetics in mice. In mice with Burkitt's lymphoma, DOX-loaded PEG-dMWCNTs and BT-PEG-dMWCNTs reduced tumor burden and increased survival similarly to free drug. Importantly, DOX toxicity was abrogated when DOX was loaded onto PEG-dMWCNTs or BT-PEG-dMWCNTs. Overall, PEG-dMWCNTs and BT-PEG-dMWCNTs represent a promising new nanocarrier platform.

SUBMITTER: Falank C

PROVIDER: S-EPMC6702103 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Development of medical-grade, discrete, multi-walled carbon nanotubes as drug delivery molecules to enhance the treatment of hematological malignancies.

Falank Carolyne C Tasset Aaron W AW Farrell Mariah M Harris Sophie S Everill Paul P Marinkovic Milos M Reagan Michaela R MR

Nanomedicine : nanotechnology, biology, and medicine 20190604

Carbon nanotubes (CNTs) hold great potential as drug delivery transporters given their large drug-binding surface area. Herein, we designed novel, multi-walled, discrete CNTs (dMWCNTs), PEGylated dMWCNTs (PEG-dMWCNTs), and bone-targeting (BT), alendronate-conjugated PEG-dMWCNTs (BT-PEG-dMWCNTs). Using zeta potential, thermogravimetric analysis, TEM, SEM, and FTIR, dMWCNTs were characterized as individual, uniform, and stable. Drug binding and release assays validated dMWCNTs as effective doxorub ...[more]

PMID: 31170511

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Project description:Microbial electrochemical systems (MESs) rely on the microbes' ability to transfer charges from their anaerobic respiratory processes to electrodes through extracellular electron transfer (EET). To increase the generally low output signal in devices, advanced bioelectrical interfaces tend to augment this problem by attaching conducting nanoparticles, such as positively charged multiwalled carbon nanotubes (CNTs), to the base carbon electrode to electrostatically attract the negatively charged bacterial cell membrane. On the other hand, some reports point to the importance of the magnitude of the surface charge of functionalized single-walled CNTs (SWCNTs) as well as the size of functional groups for interaction with the cell membrane, rather than their polarity. To shed light on these phenomena, in this study, we prepared and characterized well-solubilized aqueous dispersions of SWCNTs functionalized by either positively or negatively charged cellulose-derivative polymers, as well as with positively charged or neutral small molecular surfactants, and tested the electrochemical performance of Shewanella oneidensis MR-1 in MESs in the presence of these functionalized SWCNTs. By simple injection into the MESs, the positively charged polymeric SWCNTs attached to the base carbon felt (CF) electrode, and as fluorescence microscopy revealed, allowed bacteria to attach to these structures. As a result, EET currents continuously increased over several days of monitoring, without bacterial growth in the electrolyte. Negatively charged polymeric SWCNTs also resulted in continuously increasing EET currents and a large number of bacteria on CF, although SWCNTs did not attach to CF. In contrast, SWCNTs functionalized by small-sized surfactants led to a decrease in both currents and the amount of bacteria in the solution, presumably due to the detachment of surfactants from SWCNTs and their detrimental interaction with cells. We expect our results will help researchers in designing materials for smart bioelectrical interfaces for low-scale microbial energy harvesting, sensing, and energy conversion applications.

Dataset Information

Development of medical-grade, discrete, multi-walled carbon nanotubes as drug delivery molecules to enhance the treatment of hematological malignancies.

Publications

Development of medical-grade, discrete, multi-walled carbon nanotubes as drug delivery molecules to enhance the treatment of hematological malignancies.

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