High loading and sustained-release system of doxorubicin-carbon dots as nanocarriers for cancer therapeutics

Biomedical Materials| 24 September 2024| 10.1088/1748-605X/ad7f3a

Aswathy Prasad, Ram Prasad Sekar, Mariyam Razana Ca, Smitha Devi Sudhamani, Anagha Das, Jayakrishnan Athipettah, Lightson Ngashangva

ABSTRACT

Nanocarriers for drugs have been investigated for decades, yet it is still challenging to achieve sustained release from nanomaterials due to drug loading inefficiency and burst release. In this study, we developed novel functional carbon dots (CDs) and investigated the therapeutic efficacy by studying the loading efficiency and release behavior of the anticancer drug doxorubicin (DOX). CDs were successfully synthesized using a one-step pyrolysis method with varying concentrations of citric acid (CA) and thiourea (TU). Functional groups, morphology, particle size, and zeta potential of synthesized CT-CDs and DOX loaded CT-CDs were investigated by UV-visible, Fluorescence, DLS, Zeta Potential measurements, FTIR, and TEM. The zeta potential data revealed DOX loading onto CT-CDs by charge difference, i.e., -24.6 ± 0.44 mV (CT-CDs) and 20.57 ± 0.55 mV (DOX-CT-CDs). DOX was loaded on CDs with a loading efficiency of 88.67±0.36 %. In vitro drug release studies confirmed pH-dependent biphasic drug release, with an initial burst effect and sustained release of DOX was found to be 21.42 ± 0.28 % (pH 5), 13.30 ± 0.03 % (pH 7.4), and 13.95 ± 0.18 % (pH 9) even after 144 h at 37 °C. The CT-CDs were non-toxic and biocompatible with L929 Fibroblasts cells. The cytotoxic effect of DOX-CT-CDs showed a concentration-dependent effect after 48 h with Glioblastoma U251 cells. Flow cytometry was used to examine the cellular uptake of CT-CDs and DOX-CT-CDs in L929 and U251 cells. It was observed that the maximum CT-CD uptake was around 75% at the end of 24 h. This study showed that the synthesized fluorescent CT-CDs demonstrated a high drug loading capacity, pH-dependent sustained release of DOX, and high cellular uptake by mammalian cells. We believe this work provides practical and biocompatible CDs for chemotherapeutic drug delivery that can be applied to other drugs for certain therapeutic aims.

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