68Ga@pyridine-functionalized MCM-41 mesoporous silica: a novel radio labeled composite for diagnostic applications

2019 ◽  
Vol 107 (2) ◽  
pp. 157-164 ◽  
Author(s):  
Yousef Fazaeli ◽  
Mohammad Amin Hosseini ◽  
Mohammadreza Afrasyabi ◽  
Parviz Ashtari

Abstract Silica nanoparticles (SNPs) are known as intrinsic radiolabeling agents and offer a fast and reliable approach to deliver theranostic agents into targeted organs. Radiolabeled amorphous silica nanoparticles are of great interest to radiation oncology communities. In order to improve the performance of these nano materials in cancer diagnosis and treatment, their inherent properties, such as surface area and the ability to accumulate in cancer cells, should be enhanced. Pyridine functionalized mesoporous silica MCM-41 is known as a potential anticancer-drug delivery system with high suface area. In thiswork, in order to produce an image-guided drug delivery system for diagnostic applications, [68Ga] radionuclide was grafted on pyridine functionalized MCM-41. The nanoparticles were assessed with atomic force microscopy (AFM), paper chromatography, X-ray diffraction, FTIR spectroscopy, CHN and TGA/DTA analyses. The pharmacokinetic profile evaluation of the radiolabeled nano silica, [68Ga]-Py-Butyl@MCM-41, was done in Fibrosarcoma tumor-bearing mice. This labeled nanocomposite with appropriate blood circulation in body, high structural stability, high tumor/blood ID/g% ratio and fast excretion from the body can be proposed as an efficient nano engineered composite for upcoming tumor targeting/imaging nanotechnology-based applications.

2018 ◽  
Vol 6 (39) ◽  
pp. 6269-6277 ◽  
Author(s):  
Yaya Cheng ◽  
Xiangyu Jiao ◽  
Liang Zhao ◽  
Yang Liu ◽  
Fang Wang ◽  
...  

Inspired by aquaporins in nature, herein, a biomimetic free-blocking on-demand drug delivery system is proposed, which is constructed by controlling the wettability of the inner surface of nanochannels on mesoporous silica nanoparticles (MSNs).


Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3321
Author(s):  
Etienne J. Slapak ◽  
Lily Kong ◽  
Mouad el Mandili ◽  
Rienk Nieuwland ◽  
Alexander Kros ◽  
...  

Pancreatic ductal adenocarcinoma (PDAC) has the worst survival rate of all cancers. This poor prognosis results from the lack of efficient systemic treatment regimens, demanding high-dose chemotherapy that causes severe side effects. To overcome dose-dependent toxicities, we explored the efficacy of targeted drug delivery using a protease-dependent drug-release system. To this end, we developed a PDAC-specific drug delivery system based on mesoporous silica nanoparticles (MSN) functionalized with an avidin–biotin gatekeeper system containing a protease linker that is specifically cleaved by tumor cells. Bioinformatic analysis identified ADAM9 as a PDAC-enriched protease, and PDAC cell-derived conditioned medium efficiently cleaved protease linkers containing ADAM9 substrates. Cleavage was PDAC specific as conditioned medium from leukocytes was unable to cleave the ADAM9 substrate. Protease linker-functionalized MSNs were efficiently capped with avidin, and cap removal was confirmed to occur in the presence of PDAC cell-derived ADAM9. Subsequent treatment of PDAC cells in vitro with paclitaxel-loaded MSNs indeed showed high cytotoxicity, whereas no cell death was observed in white blood cell-derived cell lines, confirming efficacy of the nanoparticle-mediated drug delivery system. Taken together, this research introduces a novel ADAM9-responsive, protease-dependent, drug delivery system for PDAC as a promising tool to reduce the cytotoxicity of systemic chemotherapy.


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