MIL-125-based nanocarrier decorated with Palladium complex for targeted drug delivery

Abstract

The aim of this work was to provide a novel approach to designing and synthesizing a nanocomposite with significant biocompatibility, biodegradability, and stability in biological microenvironments. Hence, the porous ultra-low-density materials, metal-organic frameworks (MOFs), have been considered and the MIL-125(Ti) has been chosen due to its distinctive characteristics such as great biocompatibility and good biodegradability immobilized on the surface of the reduced graphene oxide (rGO). Based on the results, the presence of transition metal complexes next to the drug not only can reinforce the stability of the drug on the structure by preparing π-π interaction between ligands and the drug but also can enhance the efficiency of the drug by preventing the spontaneous release. The effect of utilizing transition metal complex beside drug (Doxorubicin (DOX)) on the drug loading, drug release, and antibacterial activity of prepared nanocomposites on the P. aeruginosa and S. aureus as a model bacterium has been investigated and the results revealed that this theory leads to increasing about 200% in antibacterial activity. In addition, uptake, the release of the drug, and relative cell viabilities (in vitro and in vivo) of prepared nanomaterials and biomaterials have been discussed. Based on collected data, the median size of prepared nanocomposites was 156.2 nm, and their biological stability in PBS and DMEM + 10% FBS was screened and revealed that after 2.880 min, the nanocomposite's size reached 242.3 and 516 nm respectively. The MTT results demonstrated that immobilizing PdL beside DOX leads to an increase of more than 15% in the cell viability. It is noticeable that the AST:ALT result of prepared nanocomposite was under 1.5.

Figure 1

A schematic illustration of nanocomposite fabrication.

Figure 2

(a) The FT-IR spectra of; L: (3,4-Bis(2-pyridinecarboxamido)benzophenone), PdL: (Pd(3,4-Bis(2-pyridinecarboxamido)benzophenone)), MIL125(Ti), and nanocomposite: rGO/MIL-125(Ti)@PdL@DOX. (b) The UV–Vis spectra of; L, PdL, and nanocomposite. The ¹H NMR spectra of: (c) PdL, (d) L. The PXRD spectra of e: prepared MIL-125(Ti) (f) simulated pattern.

Figure 3

The 2D, 3D, and linear roughness of nanocomposites’ poriferous surface (a) rGO/MIL-125(Ti)@PdL, (b) rGO/MIL-125(Ti)@DOX, and (c) (rGO/MIL-125(Ti)@PdL@DOX). (d) TEM results of prepared nanocomposite rGO/MIL-125(Ti)@DOX@PdL. FESEM results of prepared nanocomposites. (e) rGO/MIL-125(Ti)@DOX, (f) rGO/MIL-125(Ti)@PdL, (g) rGO/MIL-125(Ti)@DOX@PdL.

Figure 4

(a) The EDS and map of rGO/MIL-125(Ti)@DOX@PdL (a-h), rGO/MIL-125(Ti)@PdL (i-p), and rGO/MIL-125(Ti)@DOX (q-x) nanocomposites. (Max view: a, i, and q. Carbon: b, j, and r. Nitrogen: c, k, and s. Titanium: d, l, and t. Oxygen: f, n, and v. Palladium: g, o, and w. Combination: h, p, and x. EDS: e, m, and u). (b) Intracellular uptake images of DOX loaded nanocomposites by 2D fluorescence microscopy on HEK-293 (a and b), MCF-7 (c and d), MDA-MB-231 (e and f), and SW-1736 (g and h) cell lines (treatment time was 4 h).

Figure 5

The MTT assay median results after 24 and 48 h of treatment on the HEK-293 (a and c) and HT-29 cell lines (b and d). The MTT assay’s heat map results in different concentrations (0.1–50 mg/mL) of different nanocarriers and nanomaterials on the HEK-293 (e and g) and HT-29 (f and h) after 24 and 48 h of treatment. The drug release profile (time-dependent characteristic) at pH (4.5), (5.5), and (7.4) showed in i, j, and k respectively. The 2D heat-map at pH (4.5, 5.5, and 7.2) drug release profile has been revealed at (l, m, and n). (The bluish and the reddish color can indicate the lowest and the highest drug release percentage). *p value < 0.05 and **p value < 0.01.

Figure 6

High magnification of H&E counterstain of (a-d) rGO/MIL-125(Ti)@DOX@PdL, and (e–h) rGO/MIL-125(Ti)@DOX on rat liver.