Purpose The purpose of this study was to develop a multifunctional metal-organic framework-based nanocarrier that integrates targeted delivery, pH-responsive drug release, and real-time monitoring for effective cancer therapy. The research specifically investigates whether a folic acid-conjugated, amino-functionalized ZIF-90 framework can enable selective curcumin (CUR) delivery and allow electrochemical monitoring of drug release under tumour-mimicking conditions. Methods Curcumin-loaded amino-functionalized ZIF-90 was synthesised and conjugated with folic acid (FA) to obtain CUR@FA-g-ZIF-90. Structural and physicochemical properties were characterised using FT-IR and UV–Vis spectroscopy, powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), nitrogen adsorption-desorption analysis (BET), zeta potential, and dynamic light scattering (DLS). Drug loading and encapsulation efficiencies were determined spectrophotometrically. pH-responsive drug release was investigated using differential pulse voltammetry (DPV) under physiological (pH 7.4) and tumour-mimicking (pH 5.5) conditions, and release kinetics were analysed using the Korsmeyer-Peppas model. In vitro anticancer activity and selectivity were evaluated by MTT assay against MCF-7 human breast cancer cells and normal fibroblast cells. Results Spectroscopic analyses confirmed successful amino functionalization, folic acid grafting, and curcumin incorporation. PXRD patterns indicated retention of the crystalline ZIF-90 framework with reduced peak intensity after drug loading, while SEM images showed preserved morphology without significant aggregation. Nitrogen adsorption-desorption analysis revealed a marked decrease in surface area from 1220 to 520 m2 g− 1, confirming pore occupation by curcumin. Zeta potential shifted from − 5.3 mV (ZIF-90) to + 3.8 mV (aminated ZIF-90) and then to -2.8 mV (FA-g-ZIF-90) after folic acid conjugation, indicating successful surface modification. DLS showed an increase in hydrodynamic diameter from 98 nm to 124 nm following drug loading. TGA further supported CUR incorporation through additional weight-loss stages. DPV studies demonstrated slow release at pH 7.4 (30% in 48 h) and accelerated release at pH 5.5 (84% in 48 h), exhibiting biphasic behaviour. Kinetic analysis (0.5 < n < 0.8) indicated anomalous transport involving diffusion and surface erosion. In cytotoxicity studies, CUR@FA-g-ZIF-90 showed the highest cytotoxicity toward MCF-7 cells (79%) compared with free curcumin (67%) and non-targeted CUR@ZIF-90 (72%), while the carrier alone exhibited low cytotoxicity (20%). In normal fibroblast cells, all formulations produced minimal cytotoxicity (22–24%), comparable to the control, indicating good selectivity and biocompatibility. Conclusion The CUR@FA-g-ZIF-90 nanoplatform effectively combines targeted delivery, pH-responsive release, and DPV-based real-time monitoring, demonstrating significant potential for advanced cancer therapeutics. Graphical Abstract

Amino-Functionalized ZIF-90 as a Targeted and pH-Responsive Nanocarrier for Curcumin Delivery in Breast Cancer Therapy

期刊论文
发表日期：

2026年3月17日

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K. R. Jiju,
N. Kavya,
S. R. Archana,
R. Reshma

摘要

Purpose

The purpose of this study was to develop a multifunctional metal-organic framework-based nanocarrier that integrates targeted delivery, pH-responsive drug release, and real-time monitoring for effective cancer therapy. The research specifically investigates whether a folic acid-conjugated, amino-functionalized ZIF-90 framework can enable selective curcumin (CUR) delivery and allow electrochemical monitoring of drug release under tumour-mimicking conditions.

Methods

Curcumin-loaded amino-functionalized ZIF-90 was synthesised and conjugated with folic acid (FA) to obtain CUR@FA-g-ZIF-90. Structural and physicochemical properties were characterised using FT-IR and UV–Vis spectroscopy, powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), nitrogen adsorption-desorption analysis (BET), zeta potential, and dynamic light scattering (DLS). Drug loading and encapsulation efficiencies were determined spectrophotometrically. pH-responsive drug release was investigated using differential pulse voltammetry (DPV) under physiological (pH 7.4) and tumour-mimicking (pH 5.5) conditions, and release kinetics were analysed using the Korsmeyer-Peppas model. In vitro anticancer activity and selectivity were evaluated by MTT assay against MCF-7 human breast cancer cells and normal fibroblast cells.

Results

Spectroscopic analyses confirmed successful amino functionalization, folic acid grafting, and curcumin incorporation. PXRD patterns indicated retention of the crystalline ZIF-90 framework with reduced peak intensity after drug loading, while SEM images showed preserved morphology without significant aggregation. Nitrogen adsorption-desorption analysis revealed a marked decrease in surface area from 1220 to 520 m² g^− 1, confirming pore occupation by curcumin. Zeta potential shifted from − 5.3 mV (ZIF-90) to + 3.8 mV (aminated ZIF-90) and then to -2.8 mV (FA-g-ZIF-90) after folic acid conjugation, indicating successful surface modification. DLS showed an increase in hydrodynamic diameter from 98 nm to 124 nm following drug loading. TGA further supported CUR incorporation through additional weight-loss stages. DPV studies demonstrated slow release at pH 7.4 (30% in 48 h) and accelerated release at pH 5.5 (84% in 48 h), exhibiting biphasic behaviour. Kinetic analysis (0.5 < n < 0.8) indicated anomalous transport involving diffusion and surface erosion. In cytotoxicity studies, CUR@FA-g-ZIF-90 showed the highest cytotoxicity toward MCF-7 cells (79%) compared with free curcumin (67%) and non-targeted CUR@ZIF-90 (72%), while the carrier alone exhibited low cytotoxicity (20%). In normal fibroblast cells, all formulations produced minimal cytotoxicity (22–24%), comparable to the control, indicating good selectivity and biocompatibility.

Conclusion

The CUR@FA-g-ZIF-90 nanoplatform effectively combines targeted delivery, pH-responsive release, and DPV-based real-time monitoring, demonstrating significant potential for advanced cancer therapeutics.

Graphical Abstract