FOLIC ACID CONJUGATED CHITOSAN-BASED Mn2+-doped ZnS QUANTUM DOTS FOR CANCER CELL IMAGING AND TARGETED DRUG DELIVERY

The doping of impure atoms into semiconductor material inherently provided us a viable means of enhancing the fluorescence efficiency of quantum dots (QDs). Interestingly, the similarity in the ionic radii and valence state of Mn2+ and those of Zn2+ ions allowed easy substitution to take place in the host ZnS crystals. The Mn2+ ion provided a luminescence center by acting as the recombination center for the electrons and holes as charge carriers. The resultant transfer of electrons and hole charges into the electronic level of Mn2+ ions allowed for the emission of characteristic orange-red fluorescence following 4T1-6A1 transition of the Mn2+ ion. The treatment of Mn2+:ZnSQDs with UV irradiation immediately after synthesizing helpstosuppress the unwanted nonradiative relaxation activities at the surface states. Furthermore, the conjugation of Mn2+:ZnS QDs with a suitable stabilizing agent such as chitosan(CS) helps in eliminating possible toxic effect and at the same time provides suitable binding sites for the conjugation of drugs. From a biomedical point of view, the Mn:ZnS conjugated CS nanocarrier can be made to achieve active/selective targeting and imaging of diseases by attaching suitable ligands with strong binding affinity towards largely expressed receptors. In that view, Folic acid (FA), a nontoxic low-weight vitamin was found to have strong binding affinity towards folate receptors largely secreted by the cancerous cells as compared to normal. We hypothesized that the functionalization of Mn2+:ZnS conjugated CS with FA and further encapsulation withanticancer drugs can help to achieve the following: a) Enabling specific targeting of folate expressed cancer cells, b) acts as vehicle for stabilizing and transportationof drugs and c) highly intense fluorescence emission from Mn2+can be used for noninvasive imaging of cancer cells. Based on the foregoing, our objective is to synthesize a drug loaded-FA conjugated CS encapsulated-Mn2+doped ZnS (FACS-Mn:ZnS) under treatment withUV irradiation (Figure 1). Further study using the synthesized nanocomposite will be used for both invitroand histological assessment of cancer cells, its retention, distribution and bioavailability following both passive and active targeting ability towards folate overexpressed cancer cells.

Figure 1:
Schematic representation of the biofunctionalization of drug-loaded FA conjugated CS-Mn2+ doped ZnS QDs showing receptor mediated targeting, drug delivery and fluorescence imaging

Figure 2:
(A) Fluorescence mechanism FACS-Mn:ZnS QDs,(a)photon absorption and excitation(b)interstitial energy levels involving sulphur and zinc emissions,(c) Blue emission (BE) from Zn&S relaxation energy state,(d)interstitial energy trapped by Mn ions ind state and (e)orange fluorescence emission due to Mn2+ luminescence centre. (B)Fluorescence emission spectra of undoped ZnS QDs(blue line) and Mn2+ doped ZnS QDs(black line).

Figure 3:
(A) FESEM for FACS-Mn:ZnS QDs,(B) Top two images ( solution and pellet) under day light and bottom two images (solution and pellet) under UV hand lamp, and(C) EDAX spectra showing the incorporation of Mn ion impurities into the ZnS host.

Prepared by: Ibrahim Birma Bwatanglang (GS40208)