Improved Bioavailability of Curcumin in Gliadin-Protected Gold Quantum Cluster for Targeted Delivery

Abstract

This study deals with the synthesis of a gliadin-stabilized gold quantum cluster (AuQC) for the encapsulation of curcumin (CUR) and its targeted delivery to the cancer cell. CUR is an anticancer drug containing a hydrophobic polyphenol derived from the rhizome of Curcuma longa. The utilization of CUR in cancer treatment is limited because of suboptimal pharmacokinetics and poor bioavailability at the tumor site. In order to improve the bioavailability of CUR, we have encapsulated it into AuQCs stabilized by a proline-rich protein gliadin because proline-rich protein has the ability to bind a hydrophobic drug CUR. The encapsulation of CUR into the hydrophobic cavity of the protein was confirmed by various spectroscopic techniques. Compared to CUR alone, the encapsulated CUR was stable against degradation and showed higher pH stability up to pH 8.5. The encapsulation efficiency of CUR in AuQCs was calculated as 98%, which was much higher than the other reported methods. In vitro drug release experiment exhibited a controlled and pH-dependent CUR release over a period of 60 h. The encapsulated CUR-QCs exhibited less toxicity in the normal cell line (L929) and high toxicity in breast cancer (MDA-MB239). Thus, it can be used as a potential material for anticancer therapy and bioimaging.

Figure 1

Schematic representation for the targeted delivery of CUR by FA-conjugated AuQC.

Figure 2

(A) Optical absorption (black trace) and emission (blue trace, λ_ex = 380 nm) spectra of AuQC@gliadin. The inset shows the photographs of aqueous solution of AuQC@gliadin under (i) UV light and (ii) visible light. (B) TEM images of AuQC@gliadin. The inset shows the HRTEM image of AuQC@gliadin in the scale of 2 nm; (C) SAED pattern of AuQC@gliadin; and (D) binding energy of AuQC@gliadin determined from XPS.

Figure 3

(A,B) Respective absorption and emission spectra of AuQC@gliadin with different concentrations of CUR (4.4 μM to 36.4 μM). The inset of (A) shows (a) CUR in AuQC@gliadin and (b) CUR in water; (C,D) respective absorption and emission spectra of CUR with different volumes of AuQC@gliadin (100 μL to 800 μL).

Figure 4

(A) Lifetime of AuQC@gliadin and AuQC@gliadin–CUR at 680 nm emission and (B) lifetime of CUR and AuQC@gliadin–CUR at 550 nm emission.

Figure 5

(A) FTIR spectra, (B) TGA, and (C) DSC analysis of AuQC@gliadin, CUR, and AuQC@gliadin–CUR, respectively.

Figure 6

(A) Plot showing the stability of AuQC@gliadin–CUR and CUR in aqueous buffer pH 7.4 and (B) absorption spectra indicating the pH stability of AuQC@gliadin–CUR at pH 5, 6, 7, 7.4, 8.6, and 9.

Figure 7

Drug release profile showing the release percentage of CUR from AuQC@gliadin–CUR over 60 h at pH 5 and 7.4.

Figure 8

(A) Absorption spectra showing FA and FA-conjugated AuQC@gliadin–CUR (AuQC@gliadin-FA–CUR). (B) FTIR spectra of (a) FA and (b) FA-conjugated AuQC–CUR.

Figure 9

Cytotoxicity studies by the MTT assay in (A) L929 cell line and (B) MDA-MB-231 cell line.

Figure 10

Confocal fluorescence images of MDA-MB-231-breast cancer cells treated with AuQC@gliadin-FA–CUR at the first, second, and fourth hour of incubation.

Figure 11

Confocal fluorescence images of L929 cells treated with AuQC@gliadin-FA–CUR at the first, second, and fourth hour of incubation.