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. 2020 Sep 7;13(18):3950.
doi: 10.3390/ma13183950.

pH-Responsive and Biodegradable ZnO-Capped Mesoporous Silica Composite Nanoparticles for Drug Delivery

Minmin Chen  1   2 , Jinxia Hu  1   2 , Cancan Bian  1 , Chenghao Zhu  2 , Chen Chen  1 , Zhijun Guo  1 , Zhimin Zhang  1 , Godfred Amfo Agyekum  3 , Zhuoqi Zhang  3 , Xichuan Cao  1
Affiliations

pH-Responsive and Biodegradable ZnO-Capped Mesoporous Silica Composite Nanoparticles for Drug Delivery

Minmin Chen et al. Materials (Basel). .

Abstract

As a drug delivery system (DDS), traditional mesoporous silica nanoparticles (MSNs) suffer from bioaccumulation in vivo and premature drug release in systemic circulation due to low degradation rate and lack of protective gatekeeper. Herein, we developed a safe and intelligent DDS with characteristics of pH-responsive biodegradation and controlled drug release based on mesoporous silica composite nanoparticles (MSCNs) capped with ZnO quantum dots (ZnO QDs). Acidic degradable MSCNs were successfully synthesized by doping Ca2+ and PO43- into the MSNs' framework. The in vitro doxorubicin hydrochloride (DOX) release was inhibited at neutral pH 7.4 but triggered significantly at pH 5.0 due to the dissociation of ZnO caps. The internalization behavior and cytotoxicity of 4T1 cells indicated MSCNs-ZnO could efficiently deliver DOX into the cells with significant antitumor activity. Such a DDS with pH-responsive biodegradation and controlled drug release has promising potential for cancer therapy.

Keywords: ZnO QDs; mesoporous silica composite nanoparticles (MSCNs); pH-responsive biodegradability; pH-responsive drug delivery.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
Schematic illustration of ZnO-capped mesoporous silica composite nanoparticles (MSCNs) drug delivery system (DDS) and its procedure of pH-responsive degradation and drug release. DOX: doxorubicin hydrochloride.
Figure 1
Figure 1
(a) TEM images of ZnO QDs. (b) Digital photographs for power and aqueous solution (the inset image) of ZnO quantum dots (QDs) under 365 nm UV irradiation.
Figure 2
Figure 2
(a) EDS and (b) wide-angle x-ray diffraction (WAXRD) of ZnO QDs.
Figure 3
Figure 3
The percentage of dissolved Zn2+ in pH 7.4 and pH 5.0 phosphate-buffered saline (PBS) and the digital photographs (the inset images) of ZnO QDs dispersed in pH 7.4 and pH 5.0 PBS under 365 nm UV irradiation.
Figure 4
Figure 4
(a,b) TEM images, (c) size distribution of the MSCNs.
Figure 5
Figure 5
(a) Small-angle XRD (SAXRD) pattern, (b) WAXRD pattern, (c) nitrogen adsorption desorption isotherms, (d) pore size distribution diagrams of MSCNs.
Figure 6
Figure 6
(a) Element mappings of O, Si, P and Ca in MSCNs and EDS results of the MSCNs. (b) XPS spectra of MSCNs (inset image: high-resolution XPS spectrum of Ca 2p region of the MSCNs).
Figure 7
Figure 7
SEM (a1, b1, b3, b5, c1, c2, c3) and TEM (a2, b2, b4, b6, b7) images of MSCNs immersed in PBS at pH 5.0 and 7.4 for varied durations (a) 0 d, (b) 1, 3 and 7 d in pH 5.0, (c) 1, 3 and 7 d in pH 7.4. (d) The cumulative dissolved rate of Ca2+ in pH 5.0 and 7.4 PBS for 1, 3, 5 and 7 d.
Figure 8
Figure 8
Bio-TEM images of intracellular biodegradation for MSCNs culturing with 4T1 cells for 1, 3 and 7 d.
Figure 9
Figure 9
(a) TEM images of MSCNs-ZnO. (b) Photographs for power and aqueous solution (the inset image) of MSCNs-ZnO under 365 nm UV irradiation. (c) SAXRD patterns of MSCNs and MSCNs-ZnO. (d) WAXRD patterns of MSCNs and MSCNs-ZnO. (e) Nitrogen adsorption desorption isotherms of MSCNs and MSCNs-ZnO.
Figure 10
Figure 10
(a) Nitrogen adsorption desorption isotherms of MSCNs and DOX@MSCNs-ZnO. (b) Cumulative release curve of DOX@MSCNs-ZnO at pH 7.4 and pH 5.0, inset images: photographs of the DOX@MSCNs-ZnO released at pH 7.4 and pH 5.0 for 1 h. (c) Cumulative release curve of DOX@MSCNs (without ZnO nanovalves) at pH 7.4 and pH 5.0.
Figure 11
Figure 11
CLSM of DOX@MSCNs-ZnO cultured with 4T1 cells for 30 min, 1 h, 4 h and 8 h. Blue: cell nucleus staining by 2-(4-amidinophenyl)-6-indolecarbamidine dihydrochloride (DAPI). Red: DOX.
Figure 12
Figure 12
In vitro cell viability of 4T1 cells treated with (a) ZnO QDs and Zn2+, (b) MSCNs, MSCNs-ZnO, DOX@MSCNs-ZnO, DOX@MSCNs and free DOX.
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