Acid-Liable Cleavage of Doxorubicin@Plunoric-Carbon Dots in Multiplexed Bioimaging and Drug Delivery
- PDF / 9,911,849 Bytes
- 9 Pages / 595.276 x 790.866 pts Page_size
- 92 Downloads / 191 Views
Research Article Acid-Liable Cleavage of Doxorubicin@Plunoric-Carbon Dots in Multiplexed Bioimaging and Drug Delivery Eepsita Priyadarshini1 and Paulraj Rajamani1,2
Received 24 June 2020; accepted 28 October 2020; published online 16 November 2020 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. KEY WORDS: doxorubicin; bioimaging; plunoric F127; pH responsive; site-specific drug delivery.
INTRODUCTION Doxorubucin (Dox) is a broad range anthracycline drug widely used in cancer chemotherapy treatment (1). This antitumor drug functions by three basic mechanisms: intercalating between DNA base pairs thereby inhibiting gene biosynthesis; preventing RNA synthesis by binding RNA polymerase II and topoisomerase II; and generation of reactive oxygen species (ROS), which results in oxidative stress and disturbs cellular redox equilibrium resulting in cell apoptosis (2,3). Dox is basically a tetrahydroxy-anthraquinone, with an inherent fluorescence (emission at 600 nm) which makes it an ideal drug in cytotoxicity and imaging study (4,5). However, Dox has the disadvantages of low aqueous solubility, non-precise delivery and cell’s chemo resistance (1,3,6). Moreover, 1
School of Environmental Sciences, Jawaharlal Nehru University, New Delhi, 110067, India. 2 To whom correspondence should be addressed. (e–mail: [email protected]) 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-b
Data Loading...
