DPP-Cu2+ Complexes Gated Mesoporous Silica Nanoparticles For pH and Redox Dual Stimuli-Responsive Drug Delivery

Author:

Liu Zhengchun12,Chen Wei132,Ma Mingyang1,Lai Qingteng1,Zhang Yanke1

Affiliation:

1. Hunan Key Laboratory for Super Microstructure and Ultrafast Process, School of Physics and Electronics, Central South University, Changsha 410083, China

2. Department of Microbiology, School of Basic Medical Science, Central South University, Changsha 410013, China

3. Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha 410008, China

Abstract

Objective: A simple pH and redox dual stimuli-responsive diketopyrrolopyrrole (DPP)-Cu2+ complexes gated mesoporous silica nanoparticles (MSN) were prepared for precise drug delivery and controlled drug release. Method: MSN was prepared by sol-gel method and then laminated. Carboxylic acid (CA)-Pyrrolo[3,4-c] pyrrole-1,4-dione, 2,5-dihydro-3,6-di-2-pyridinyl (PyDPP) was grafted onto the surface of amino-functionalized MSN (MSN-NH2) through a simple amide reaction and then complexed with Cu2+ to form gated molecules after doxorubicin (DOX) loading. Results: Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Low-angle X-ray diffraction (XRD) showed that MSN with uniform particle size (100 nm) and porous structure was successfully prepared. The prepared MSN, MSN-NH2, and MSN-DPP were fully characterized by Zeta potential, Fourier transforms infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and nitrogen adsorption-desorption. High DOX-loading capacity (18.22%) and encapsulation efficiency (89.16%) were achieved by optimizing the mass ratio of MSN to DOX. Release studies showed that the gated molecules of our designed DPP-Cu2+ complexes had a good blocking effect under physiological conditions (the cumulative release rate of drugs within 24 hours was only 4.18%) and responded well to the pH and redox glutathione (GSH) dual stimuli. In vitro cytotoxicity assay showed that MSN-DPP-Cu2+ had good biocompatibility in both Hep G2 cells and L02 cells (the relative cell viability of both cells within 48 hours was above 97%), and the MSN-DPP-Cu2+@DOX could be triggered for efficient drug release in Hep G2 cells. Conclusion: The MSN-DPP-Cu2+ described in this research may be a good delivery system for the controlled release of antitumor drugs and can provide a potential possibility for clinical application in the future.

Publisher

Bentham Science Publishers Ltd.

Subject

Pharmacology,Molecular Medicine,Drug Discovery,Biochemistry,Organic Chemistry

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