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Novel graphene quantum dot (GQD) based charge-reversal nanomaterial could improve nucleus-targeted drug delivery and efficiency controllable photodynamic therapy

23 Jul | By Biophotonics.World
Novel graphene quantum dot (GQD) based charge-reversal nanomaterial could improve nucleus-targeted drug delivery and efficiency controllable photodynamic therapy
Figure 1. (A) Surface charges of the Nitrogen doped graphene quantum dots (N-GQD-DOX) modified with APTES at various concentrations (0.42, 0.84, 1.68, 2.52 and 3.36 μM, labeled as a to e) at different pH values analyzed by a Nano ZS Zetasizer, (B) DOX distribution in nuclei for free DOX, N-GQD-DOX and N-GQD-DOX-APTES. Red fluorescence, which was attributed to DOX, for N-GQDDOX-APTES was more intense in the nuclei regions, (C) Reactive oxygen species (ROS) generation by free DOX, N-GQD-DOX and N-GQD-DOX-APTES in MDA-MB-231 cells, (D) Cartoon showing that N-GQD-DOX-APTES improve both nucleus-targeting drug delivery and PDT efficacy according to the results of this cell study.
Image source: Quan Liu

Researchers from the Nanyang Technological University (Singapore) (NTU/SG) and Oakland University (USA) (OU/USA) have developed and evaluated multi-functional materials, i.e. N-GQD-DOX-APTES, as a potential photosensitizer and nucleus-targeted drug carrier for cancer therapy.The work has been published in the Journal of Biophotonics for the month of June, one of the most important international journals in the field of application of photonic technologies in biomedicine.

 

An increase in the accumulation of anticancer drugs in cell nuclei improves cancer treatment. Consequently, a nuclear-targeted drug carrier is desirable to effective transport the drug. Photodynamic therapy (PDT) is a clinically approved therapeutic modality used for the treatment of neoplastic diseases. Therefore the integration of the two therapeutic strategies into one nano platform could combine the advantages of both and enhancement the treatment outcome. 

 

In this paper, the authors select the small-size nitrogen doped Graphene quantum dots (N-GQD) as the carrier for delivering a common cancer drug, DOX, and graft a charge reversal agent (3-Aminopropyl) triethoxysilane (APTES) on the surfaceof N-GQD-DOX to enhance the pH-sensitive release of anti-cancer drug in cell nuclei. In the drug transport process, the negatively charged drug carrier exhibits prolonged circulation time in blood due to the repelling interaction with negatively charged proteins. Moreover, once transported into the acidic tumor microenvironment, a positively charged drug carrier after charge reversal shows increased capacity to be internalized by tumor cells viathe negative surface of cell membrane. This pH dependent charge-reversal property of N-GQD-DOX-APTESis shown in Figure 1(A) and the intracellular and nucleus DOX accumulation after drug release in MDA-MB-231 cells is shown in Figure 1(B).

 

Furthermore, the authors show that N-GQD can used as a novel photosensitizing agent via the photo-excited process for PDT to kill cancer cells and its ROS generation performance can be tailored by changing the amount of nitrogen to create more defect sites. Both2´, 7´- Dichlorofluorescein diacetate (DCFDA)and DHE dye are used to image the generation of ROS as shown in Figure 1(C).

 

The above results provide adequate evidence indicating the proposed nanomaterial, i.e. N-GQD-DOX-APTES, as a potential photosensitizer with controllable PDT efficiency.More importantly, after grafting with APTES, which is a charge reversal agent, N-GQD-DOX-APTESshows increased drug uptake by cell nuclei such that the cancer drug, can directly target on nuclei for improved treatment as illustrated in Figure 1(D). “These results suggest that, the synthesis of this multi-functional nanomaterial could be further developed to achieve dual therapies especially for tumors resistant to a single type of treatment,” they conclude.

 

 

AuthorsJian Ju, Sagar Regmi, Afu Fu, Sierin Lim and Quan Liu

Source:Journal of Biophotonics

Related journal article:  https://doi.org/10.1002/jbio.201800367

Area of application: Oncology, Drug delivery

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