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Acid-Liable Cleavage of Doxorubicin@Plunoric-Carbon Dots in Multiplexed Bioimaging and Drug Delivery

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Abstract

This study reports the generation of novel, aqueous-dispersible plunoric-CD nanoconjugates encapsulating doxorubicin (Dox). The fluorescent CD were conjugated with plunoric F127 to form biocompatible delivery matrix and were further loaded with fluorescent Dox molecule. The resulting particles were analyzed for multiplexed bioimaging and targeted drug delivery. Physicochemical and optical characterization demonstrated discrete fluorescence from CD (blue emission) and Dox (orange emission) counterparts. In vitro drug release profile signifies higher and rapid release of Dox from Dox@Plu-CD under acidic conditions compared to physiological pH. Thus, the acid liable Dox@Plu-CD linkage can easily break in the cytosol of tumor cells because of low pH compared to normal cells thus conferring minimal damage to healthy cells. Moreover, results form in vitro cell viability assay suggest the cyto-compatibility of Plu-CD delivery matrix to HEK293 and HeLa cell lines. However, Dox@Plu-CD induced cell death and morphological alterations in HeLa cell lines, signifying pH-responsive effect of the prepared complex. Confocal imaging signified that Dox@Plu-CD effectively penetrates HeLa cells, and the released Dox binds to the cell nucleus and induces oxidative stress. The prepared Dox@Plu-CD thus behaved as efficient fluorescent probes allowing multiplexed bioimaging (blue and orange) of HeLa cells along with improved therapeutic potential.

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Abbreviations

Dox:

Doxorubicin

Plu:

Plunoric

CD:

Carbon dots

ROS:

Reactive oxygen species

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

FBS:

Fetal bovine serum

DLS:

Dynamic light scattering

NCCS:

National Centre for Cell Science

Rh :

Hydrodynamic radius

PEG:

Polyethylene glycol

PBS:

Phosphate-buffered saline

DCFDA:

2′,7′-Dichlorofluorescein-diacetate

RPMI:

Roswell Park Memorial Institute Medium

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Acknowledgements

EP is thankful to Department of Science and Technology-Science and Engineering Board, New Delhi, India, for fellowship under National Postdoctoral Scheme (PDF/2017/000024). Authors are grateful to Advanced Instrumentation Research Facility, Jawaharlal Nehru University, New Delhi, for confocal imaging studies.

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  1. School of Environmental Sciences, Jawaharlal Nehru University, New Delhi, 110067, India

    Eepsita Priyadarshini & Paulraj Rajamani

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  1. Eepsita Priyadarshini
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Correspondence to Paulraj Rajamani.

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Priyadarshini, E., Rajamani, P. Acid-Liable Cleavage of Doxorubicin@Plunoric-Carbon Dots in Multiplexed Bioimaging and Drug Delivery. AAPS PharmSciTech 21, 322 (2020). https://doi.org/10.1208/s12249-020-01871-1

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  • DOI: https://doi.org/10.1208/s12249-020-01871-1

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