Theranostic mesoporous silica nanoparticles made of multi-nuclear gold or carbon quantum dots particles serving as pH responsive drug delivery system (original) (raw)
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Theranostics, 2015
Increasing cell survival in stem cell therapy is an important challenge for the field of regenerative medicine. Here, we report theranostic mesoporous silica nanoparticles that can increase cell survival through both diagnostic and therapeutic approaches. First, the nanoparticle offers ultrasound and MRI signal to guide implantation into the peri-infarct zone and away from the most necrotic tissue. Second, the nanoparticle serves as a slow release reservoir of insulin-like growth factor (IGF)-a protein shown to increase cell survival. Mesenchymal stem cells labeled with these nanoparticles had detection limits near 9000 cells with no cytotoxicity at the 250 µg/mL concentration required for labeling. We also studied the degradation of the nanoparticles and showed that they clear from cells in approximately 3 weeks. The presence of IGF increased cell survival up to 40% (p<0.05) versus unlabeled cells under in vitro serum-free culture conditions.
Acta Biomaterialia, 2016
The potential use of human Decidua-derived mesenchymal stem cells (DMSCs) as a platform to carry mesoporous silica nanoparticles in cancer therapy has been investigated. Two types of nanoparticles were evaluated. The nanoparticles showed negligible toxicity to the cells, a fast uptake and a long retention inside them. Nanoparticle location in the cell was studied by colocalization with the lysosomes. Moreover, the in vitro and in vivo migration of DMSCs towards tumors was not modified by the evaluated nanoparticles. Finally, DMSCs transporting doxorubicin-loaded nanoparticles were capable of inducing cancer cell death in vitro. Statement of Significance The use of nanotechnology for anticancer drug delivery has recently attracted great interest. Nanoparticles such as mesoporous silica nanoparticles (MSNs) can reach tumors, either by passive targeting , through the enhanced permeability and retention (EPR) effect, or active targeting, through the func-tionalization of nanoparticle surface. However, nanotechnology has not yet achieved the expected results in improving drug targeting, highlighting the need for a better localization of the nanoparticles in the tumors. Human mesenchymal stem cells from the decidua of the human placenta (DMSCs) have been observed to migrate towards tumors in a preclinical model of breast cancer. Moreover, they have been shown to inhibit growth of primary tumors and development of new tumors. In this work, combining MSNs and DMSCs, we have studied for the first time whether placental stem cells could be employed as a platform to load nanoparticles and carry them towards tumors for future anticancer therapies.
VEGF₁₂₁-conjugated mesoporous silica nanoparticle: a tumor targeted drug delivery system
ACS applied materials & interfaces, 2014
The vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) signaling cascade plays a critical role in tumor angiogenesis and metastasis and has been correlated with several poorly prognostic cancers such as malignant gliomas. Although a number of anti-VEGFR therapies have been conceived, inefficient drug administration still limits their therapeutic efficacy and raises concerns of potential side effects. In the present work, we propose the use of uniform mesoporous silica nanoparticles (MSNs) for VEGFR targeted positron emission tomography imaging and delivery of the anti-VEGFR drug (i.e., sunitinib) in human glioblastoma (U87MG) bearing murine models. MSNs were synthesized, characterized and modified with polyethylene glycol, anti-VEGFR ligand VEGF121 and radioisotope (64)Cu, followed by extensive in vitro, in vivo and ex vivo studies. Our results demonstrated that a significantly higher amount of sunitinib could be delivered to the U87MG tumor by targeting VEGFR when comp...
Small, 2015
The results of a systematic investigation of the role of serum proteins on the interaction of silica nanoparticles (NP) doped in their bulk with fluorescent molecules (IRIS Dots, 50 nm in size), with human mesenchymal stem cells (hMSCs) are reported. The suspension of IRIS Dots in bare Dulbecco-Modified Eagle's Medium (DMEM) results in the formation of large agglomerates (ca. 1.5 µm, by dynamic light scattering), which become progressively smaller, down to ca. 300 nm in size, by progressively increasing the fetal bovine serum (FBS) content of the solutions along the series 1.0, 2.5, 6.0 and 10.0% v/v. Such difference in NP dispersion is maintained in the external cellular microenvironment, as observed by confocal microscopy and transmission electron microscopy. As a consequence of the limited diffusion of proteins in the inter-NP spaces, the surface of NP agglomerates is coated by a protein corona independently of the agglomerate size/FBS concentration conditions (ζ-potential and UV circular dichroism measurements). The protein corona appears not to be particularly relevant for the uptake of IRIS Dots by hMSCs, whereas the main role in determining the internalization rate is played by the absence/presence of serum proteins in the extra-cellular media.
RSC Advances, 2023
A new and efficient theranostic nanoplatform was developed via a green approach for targeted cancer therapy and fluorescence imaging, without the use of any anticancer chemotherapeutic drugs. Toward this aim, monodisperse and spherical mesoporous silica nanoparticles (MSNs) of approximately 50 nm diameter were first synthesized using the sol-gel method and loaded with hydrothermally synthesized anticancer carbon dots (CDs). The resulting MSNs-CDs were then functionalized with chitosan and targeted by an anti-MUC1 aptamer, using the glutaraldehyde cross-linker, and fully characterized by TEM, FE-SEM, EDS, FTIR, TGA, XRD, and BET analysis. Potent and selective anticancer activity was obtained against MCF-7 and MDA-MB-231 cancer cells with the maximum cell mortalities of 66.2 ± 1.97 and 71.8 ± 3%, respectively, after 48 h exposure with 100 mg mL −1 of the functionalized MSNs-CDs. The maximum mortality of 40.66 ± 1.3% of normal HUVEC cells was obtained under the same conditions. Based on the results of flowcytometry analysis, the apoptotic mediated cell death was recognized as the main anticancer mechanism of the MSNs-CDs. The fluorescence imaging of MCF-7 cancer cells was also studied after exposure with MSNs-CDs. The overall results indicated the high potential of the developed nanoplatform for targeted cancer theranostics.
Nanomedicine (London, England), 2018
To assess functional effects of silica nanoparticles (SiO-NPs) on human mesenchymal stem cell (hMSC) cardiac integration potential. SiO-NPs were synthesized and their internalization effects on hMSCs analyzed with particular emphasis on interaction of hMSCs with the cardiac environment Results: SiO-NP internalization affected the area and maturation level of hMSC focal adhesions, accounting for increased in vitro adhesion capacity and augmented engraftment in the myocardial tissue upon cell injection in infarcted isolated rat hearts. SiO-NP treatment also enhanced hMSC expression of Connexin-43, favoring hMSC interaction with cocultured cardiac myoblasts in an ischemia-like environment. These findings provide strong evidence that SiO-NPs actively engage in mediating biological effects, ultimately resulting in augmented hMSC acute cardiac integration potential.
Mesoporous silica nanoparticles in medicine—Recent advances
MSNs have attracted increasing interest as drug carriers due to promising in vivo results in small-animal disease models, especially related to cancer therapy. In most cases small hydrophobic drugs have been used, but recent in vitro studies demonstrate that MSNs are highly interesting for gene delivery applications. This review covers recent advances related to the therapeutic use of mesoporous silica nanoparticles (MSNs) administered intravenously, intraperitoneally or locally. We also cover the use of MSNs in alternative modes of therapy such as photodynamic therapy and multidrug therapy. We further discuss the current understanding about the biodistribution and safety of MSNs. Finally, we critically discuss burning questions especially related to experimental design of in vivo studies in order to enable a fast transition to clinical trials of this promising drug delivery platform.
Mesoporous Silica Nanoparticles as a Delivery System for Hydrophobic Anticancer Drugs
Small, 2007
Tumblerlike magnetic/fluorescein isothiocyanate (FITC)-labeled mesoporous silica nanoparticles, Mag-Dye@MSNs, have been developed, which are composed of silica-coated core-shell superparamagnetic iron oxide (SPIO@SiO 2 ) nanoparticles co-condensed with FITC-incorporated mesoporous silica. Mag-Dye@MSNs can label human mesenchymal stem cells (hMSCs) through endocytosis efficiently for magnetic resonance imaging (MRI) in vitro and in vivo, as manifested by using a clinical 1.5-T MRI system with requirements of simultaneous low incubation dosage of iron, low detection cell numbers, and short incubation time. Labeled hMSCs are unaffected in their viability, proliferation, and differentiation capacities into adipocytes and osteocytes, which can still be readily detected by MRI. Moreover, a higher MRI signal intensity decrease is observed in Mag-Dye@MSN-treated cells than in SPIO@SiO 2 -treated cells. This is the first report that MCM-41-type MSNs are advantageous to cellular uptake, as manifested by a higher labeling efficiency of Mag-Dye@MSNs than SPIO@SiO 2 .