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PH-sensitive and bubble-generating mesoporous silica-based nanoparticles for enhanced tumor combination therapy.

ABSTRACT: Chemotherapy has been a major option in clinic treatment of malignant tumors. However, single chemotherapy faces some drawbacks, such as multidrug resistance, severe side effects, which hinder its clinic application in tumor treatment. Multifunctional nanoparticles loading with chemotherapeutic agent and photosensitizer could be a promising way to efficiently conduct tumor combination therapy. In the current study, a novel pH-sensitive and bubble-generating mesoporous silica-based drug delivery system (denoted as M(a)D@PI-PEG-RGD) was constructed. Ammonium bicarbonate (NH₄HCO₃; abc) and chemotherapeutic agent doxorubicin (DOX) were loaded into the pores of mesoporous silica. Indocyanine green (ICG) as a photothermal and photodynamic agent was loaded onto the polydopamine (PDA) layer surface. The synthesized nanoparticles displayed a narrow polydispersity (PDI) and small particle size as characterized through dynamic light scattering-autosizer analysis. The nanoparticles also showed high targeting efficacy through RGD modification as indicated by cellular uptake and animal studies. DOX release analysis confirmed that the nanoparticles were pH-dependent and that NH₄HCO₃ accelerated drug release. At the same time, the nanoparticles had obvious photothermal and photodynamic effects performed by ICG which restrained tumor growth remarkably. In summary, the multifunctional nanoparticles presented a promising system for combination therapy.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC7893139 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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pH-sensitive and bubble-generating mesoporous silica-based nanoparticles for enhanced tumor combination therapy.

Zhang Zhiming Z Huang Chenlu C Zhang Li L Guo Qing Q Qin Yu Y Fan Fan F Li Boxuan B Xiao Bao B Zhu Dunwan D Zhang Linhua L

Acta pharmaceutica Sinica. B 20200902 2

Chemotherapy has been a major option in clinic treatment of malignant tumors. However, single chemotherapy faces some drawbacks, such as multidrug resistance, severe side effects, which hinder its clinic application in tumor treatment. Multifunctional nanoparticles loading with chemotherapeutic agent and photosensitizer could be a promising way to efficiently conduct tumor combination therapy. In the current study, a novel pH-sensitive and bubble-generating mesoporous silica-based drug delivery ...[more]

PMID: 33643828

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Project description:Tunable glutathione (GSH)-sensitive hollow mesoporous silica nanoparticles (HMSiO2 NPs) were developed using a structural difference-based selective etching strategy. These organosilica hollow nanoparticles contained disulfide linkages (S-S) in the outer shell which were degraded by GSH. The particles were compared with their nonGSH-sensitive tetraethyl orthosilicate (TEOS) HMSiO2 counterparts in terms of their synthesis method, characterization, doxorubicin (DOX) release profile, and in vitro cytotoxicity in MCF-7 breast cancer cells. Transmission electron microscopy (TEM) of the particles indicated that the fabricated HMSiO2 NPs had an average diameter of 130?±?5?nm. Thermogravimetric analysis (TGA) revealed that GSH-sensitive particles had approximately 5.3% more weight loss than TEOS HMSiO2 NPs. Zeta potential of these redox-responsive particles was -23?±?1?mV at pH?6 in deionized (DI) water. Nitrogen adsorption-desorption isotherm revealed that the surface area of the hollow mesoporous nanoreservoirs was roughly 446?±?6?m2?g-1 and the average diameter of the pores was 2.3?±?0.5?nm. TEM images suggest that the nanoparticles started to lose mass integrity from Day 1. The particles showed a high loading capacity for DOX (8.9?±?0.5%) as a model drug, due to the large voids existing in the hollow structures. Approximately 58% of the incorporated DOX released within 14?days in phosphate buffered saline (PBS) at pH?6 and in the presence of 10?mM of GSH, mimicking intracellular tumor microenvironment while release from TEOS HMSiO2 NPs was only c.a. 18%. The uptake of these hollow nanospheres by MCF-7 cells and RAW 264.7 macrophages was evaluated using TEM and confocal microscopy. The nanospheres were shown to accumulate in the endolysosomal compartments after incubation for 24?h with the maximum uptake of c.a. 2.1?±?0.3% and 5.2?±?0.4%, respectively. Cytotoxicity of the nanospheres was investigated using CCK-8 assay. Results indicate that intact hollow particles (both GSH-sensitive and TEOS HMSiO2 NPs) were nontoxic to MCF-7 cells after incubation for 24?h within the concentration range of 0-1000??g?ml-1. DOX-loaded GSH-sensitive nanospheres containing 6??g?ml-1 of DOX killed c.a. 51% of MCF-7 cells after 24?h while TEOS HMSiO2 NPs killed c.a. 20% with the difference being statistically significant. Finally, cytotoxicity data in RAW 264.7 macrophages and NIH 3?T3 fibroblasts shows that intact GSH-sensitive HMSiO2 NPs did not show any toxic effects on these cells with the concentrations equal or <125??g?ml-1.

Dataset Information

PH-sensitive and bubble-generating mesoporous silica-based nanoparticles for enhanced tumor combination therapy.

Publications

pH-sensitive and bubble-generating mesoporous silica-based nanoparticles for enhanced tumor combination therapy.

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