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. 2025 Feb 14:20:1965-1981.
doi: 10.2147/IJN.S489418. eCollection 2025.

Folate-Functionalized CS/rGO/NiO Nanocomposites as a Multifunctional Drug Carrier with Anti-Microbial, Target-Specific, and Stimuli-Responsive Capacities

Affiliations

Folate-Functionalized CS/rGO/NiO Nanocomposites as a Multifunctional Drug Carrier with Anti-Microbial, Target-Specific, and Stimuli-Responsive Capacities

Sreekanth Reddy Obireddy et al. Int J Nanomedicine. .

Abstract

Purpose: This study reports the synthesis of surface-modified chitosan (CS) coated with reduced graphene oxide/nickel oxide (rGO/NiO) as a multifunctional drug carrier with anti-microbial, target-specific, and stimuli-responsive capacities. CS, rGO, and NiO nanoparticles are selected due to their pH-responsiveness, large surface area, and ROS generating-capacity, respectively.

Methods: The CS/rGO/NiO nanocomposites (NCs) are synthesized using a solvothermal approach. Glutaraldehyde is used to crosslink CS and rGO/NiO to enhance the stability of the NCs. Structural properties, magnetic properties, antimicrobial activity, drug release sustainability and toxicity of the NCs are evaluated.

Results: The NCs show good biocompatibility, excellent magnetic properties, good target specificity, and remarkable cell growth inhibitory effects. The release of doxorubicin (DOX) from the drug-loaded NCs at pH 5.0 (~98.6%) is much higher than that at pH 7.4 (~9.6%). Furthermore, the NCs inhibit the growth of A549 and MCF7 cells, causing the viability of A549 and MCF7 to drop to 12.3% and 7.1%, respectively. By using zebrafish embryos as a model, no detectable change is observed in the survival rate of the embryos after NC treatment.

Conclusion: The NCs exhibit multifunctional, target-specific, and pH-responsive characteristics. These properties make the NCs a promising candidate for use in drug delivery applications.

Keywords: biopolymer; drug delivery; folate receptor; nanoparticles; nickel oxide.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
FTIR spectra of GO, CS, NiO, rGO/NiO and CS/rGO/NiO.
Figure 2
Figure 2
XRD patterns for synthesized GO, CS, NiO, rGO/NiO (1, 3, 5%) and CS/rGO/NiO (5, 10, 15%).
Figure 3
Figure 3
FE-SEM images of GO, CS, NiO, and CS/rGO/NiO and the corresponding EDX patterns.
Figure 4
Figure 4
(AC) HR-TEM images, with different magnifications, of CS/rGO/NiO. (D) The SAED pattern of CS/rGO/NiO.
Figure 5
Figure 5
XPS spectrum of CS/rGO/NiO and the high-resolution spectra of Ni 2p, Ni 2s, Ni 3p, C 1s and O 1s peaks.
Figure 6
Figure 6
The room temperature M-H loop of CS/rGO/NiO.
Figure 7
Figure 7
Antimicrobial activity of GO, CS, NiO, rGO/NiO and CS/rGO/NiO against (A) bacteria and (B) fungi. Treatment with DMSO alone was used for the negative control. Treatment with azithromycin (for bacteria) and fluconazole (for fungi) was used for the positive control. Within each species, different letters above each bar indicate significant differences among treatments (ANOVA, Tukey’s HSD test, p < 0.05).
Figure 8
Figure 8
CLSM images of biofilms exposed to different samples at 37 °C for 24 h. In the images, live microbes emit green light. Dead cells are not colored. Treatment with DMSO alone was used as the control.
Figure 9
Figure 9
UV-vis absorption spectra of DOX and DOX-loaded CS/rGO/NiO/FA NCs.
Figure 10
Figure 10
(A) Changes in the efficiency of DOX loading into CS/rGO/NiO/FA NCs at different initial DOX concentrations. (B) The percentage of drug release from DOX-loaded CS/rGO/NiO/FA NCs at different pH values.
Figure 11
Figure 11
The viability of (A) A549 and (B) MCF7 cells upon treatment with different concentrations of CS/rGO/NiO, DOX-loaded CS/rGO/NiO and DOX-loaded CS/rGO/NiO/FA.
Figure 12
Figure 12
Fluorescence images of stained (A) A549 and (B) MCF7 cells after treatment with CS/rGO/NiO, DOX-loaded CS/rGO/NiO, and DOX-loaded CS/rGO/NiO/FA. Untreated cells are used as the control.
Figure 13
Figure 13
The hatching rates of zebrafish embryos, observed at (A) 0 and (B) 72 hpf, after treatment with GO, CS, NiO, rGO/NiO and CS/rGO/NiO. The control group receives no treatment.
Figure 14
Figure 14
Microscopic images of the zebrafish taken, after different time intervals (24 h, 36 h, 48 h and 72 h), upon microinjection of different samples into zebrafish embryos: (a) control, (b) GO, (c) CS, (d) NiO, (e) rGO/NiO and (f) CS/rGO/NiO. The control group receives no treatment.

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