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Biodegradable Hollow Mesoporous Silica Nanoparticles for Regulating Tumor Microenvironment and Enhancing Antitumor Efficiency.

ABSTRACT: There is accumulating evidence that regulating tumor microenvironment plays a vital role in improving antitumor efficiency. Herein, to remodel tumor immune microenvironment and elicit synergistic antitumor effects, lipid-coated biodegradable hollow mesoporous silica nanoparticle (dHMLB) was constructed with co-encapsulation of all-trans retinoic acid (ATRA), doxorubicin (DOX) and interleukin-2 (IL-2) for chemo-immunotherapy. The nanoparticle-mediated combinational therapy provided a benign regulation on tumor microenvironment through activation of tumor infiltrating T lymphocytes and natural killer cells, promotion of cytokines secretion of IFN-γ and IL-12, and down-regulation of immunosuppressive myeloid-derived suppressor cells, cytokine IL-10 and TGF-β. ATRA/DOX/IL-2 co-loaded dHMLB demonstrated significant tumor growth and metastasis inhibition, and also exhibited favorable biodegradability and safety. This nanoplatform has great potential in developing a feasible strategy to remodel tumor immune microenvironment and achieve enhanced antitumor effect.

SUBMITTER: Kong M

PROVIDER: S-EPMC5595131 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Biodegradable Hollow Mesoporous Silica Nanoparticles for Regulating Tumor Microenvironment and Enhancing Antitumor Efficiency.

Kong Miao M Tang Jiamin J Qiao Qi Q Wu Tingting T Qi Yan Y Tan Songwei S Gao Xueqin X Zhang Zhiping Z

Theranostics 20170723 13

There is accumulating evidence that regulating tumor microenvironment plays a vital role in improving antitumor efficiency. Herein, to remodel tumor immune microenvironment and elicit synergistic antitumor effects, lipid-coated biodegradable hollow mesoporous silica nanoparticle (dHMLB) was constructed with co-encapsulation of all-trans retinoic acid (ATRA), doxorubicin (DOX) and interleukin-2 (IL-2) for chemo-immunotherapy. The nanoparticle-mediated combinational therapy provided a benign regul ...[more]

PMID: 28900509

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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 μg ml-1. DOX-loaded GSH-sensitive nanospheres containing 6 μg 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 μg ml-1.

Project description:Introduction: Dental erosion and abrasion pose significant clinical challenges, often leading to exposed dentinal tubules and dentine demineralization. The aim of this study was to analyse the efficacy of quercetin-encapsulated hollow mesoporous silica nanocomposites (Q@HMSNs) on the prevention of dentine erosion and abrasion. Method: Q@HMSNs were synthesized, characterized, and evaluated for their biocompatibility. A total of 130 dentine specimens (2 mm × 2 mm × 2 mm) were prepared and randomly distributed into 5 treatment groups (n = 26): DW (deionized water, negative control), NaF (12.3 mg/mL sodium fluoride, positive control), Q (300 μg/mL quercetin), HMSN (5.0 mg/mL HMSNs), and Q@HMSN (5.0 mg/mL Q@HMSNs). All groups were submitted to in vitro erosive (4 cycles/d) and abrasive (2 cycles/d) challenges for 7 days. The specimens in the DW, NaF, and Q groups were immersed in the respective solutions for 2 min, while treatment was performed for 30 s in the HMSN and Q@HMSN groups. Subsequently, the specimens were subjected to additional daily erosion/abrasion cycles for another 7 days. The effects of the materials on dentinal tubule occlusion and demineralized organic matrix (DOM) preservation were examined by scanning electron microscopy (SEM). The penetration depth of rhodamine B fluorescein into the etched dentine was assessed using confocal laser scanning microscopy (CLSM). The erosive dentine loss (EDL) and release of type I collagen telopeptide (ICTP) were measured. The data were analysed by one-way analysis of variance (ANOVA) with post hoc Tukey's test (α = 0.05). Results: Q@HMSNs were successfully synthesized and showed minimal toxicity to human dental pulp stem cells (HDPSCs) and gingival fibroblasts (HGFs). Q@HMSNs effectively occluded the dentinal tubules, resulting in a thicker DOM in the Q@HMSN group. The CLSM images showed more superficial penetration in the HMSN and Q@HMSN groups than in the quercetin, NaF, and DW groups. The Q@HMSN group exhibited a significantly lower EDL and reduced ICTP levels compared to the other groups (p < 0.05). Conclusion: Q@HMSNs hold promise for inhibiting dentine erosion and abrasion by promoting tubule occlusion and DOM preservation.

Dataset Information

Biodegradable Hollow Mesoporous Silica Nanoparticles for Regulating Tumor Microenvironment and Enhancing Antitumor Efficiency.

Publications

Biodegradable Hollow Mesoporous Silica Nanoparticles for Regulating Tumor Microenvironment and Enhancing Antitumor Efficiency.

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