scholarly journals Tumor Targeting Effect of Triphenylphosphonium Cations and Folic Acid Coated with Zr-89-Labeled Silica Nanoparticles

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2922
Author(s):  
Gun Gyun Kim ◽  
Jun Young Lee ◽  
Pyeong Seok Choi ◽  
Sang Wook Kim ◽  
Jeong Hoon Park

In this study, we investigated the tumor targeting effect in cancer cells using triphenylphosphonium (TPP) cations, which are accumulated by differences in membrane potential, and folic acid (FA), which is selectively bound to overexpressed receptors on various cancer cells. We used Food and Drug Administration (FDA)-approved silica nanoparticles (SNPs) as drug carriers, and SNPs conjugated with TPP and FA (STFs) samples were prepared by introducing different amounts of TPP and FA onto the nanoparticle surfaces. STF-1, 2, 3, 4 and 5 are named according to the combination ratio of TPP and FA on the particle surface. To confirm the tumor targeting effect, 89Zr (t1/2 = 3.3 days) was coordinated directly to the silanol group of SNP surfaces without chelators. It was shown that the radiochemical yield was 69% and radiochemical purity was >99%. In the cellular uptake evaluation, SNPs with the most TPP (SFT-5) and FA (SFT-1) attached indicated similar uptake tendencies for mouse colon cancer cells (CT-26). However, the results of the cell internalization assay and measurement of positron emission tomography (PET) images showed that SFT-5 had more affinity for the CT-26 tumor than other samples the TPP ratio of which was lower. Consequently, we confirmed that TPP ligands affect target cancer cells more than FA, which means that cell membrane potential is significantly effective for tumor targeting.

2020 ◽  
Vol Volume 15 ◽  
pp. 3433-3445
Author(s):  
Mengmeng Han ◽  
Xiaoman Ji ◽  
Jianfei Li ◽  
Zhiming Ge ◽  
Bin Luo ◽  
...  

Author(s):  
Mei-Xia Zhao ◽  
Di-Feng Chen ◽  
Xue-Jie Zhao ◽  
Lin-Song Li ◽  
Yong-Fang Liu

Targeted nanocarrier can selectively deliver anti-tumor drugs to cancer sites improving drug efficiency. Accordingly, a targeted nanocarrier (MSN-FA) was synthesized based on folic acid (FA) modified mesoporous silica nanoparticles (MSNs). These loaded with 10-hydroxycamptothecin (HCPT) to obtain the nano-drug MSN-FA@HCPT. These nanocarriers were characterized by transmission electron microscopy (TEM), zeta potential, ultraviolet-visible spectroscopy (UV-Vis), fourier transform infrared spectroscopy (FT-IR), and thermogravimetric analysis (TGA). Notably, the nanocarriers were nearly spherical before and after loading HCPT and exhibited good dispersibility. Also, folate receptor (FR) over-expressing HeLa cells and FR deficient HepG2 cells were used to evaluate in vitro cellular uptake and cytotoxicity of MSN-FA@HCPT and MSN@HCPT. Interestingly, FA-modified nanocarriers enhanced the cytotoxicity of HCPT by improving drug targeting to tumor cells. Also, apoptotic and mitochondrial membrane potential (MMP) reducing effects of MSN-FA@HCPT were more prominent than the MSNs without FA modification. MSN-FA@HCPT can be excellent drug carriers with profound biomedical applications.


2020 ◽  
Vol 19 ◽  
pp. 153303382096211
Author(s):  
Ding Wang ◽  
Dan Yu ◽  
Xueshibojie Liu ◽  
Qian Wang ◽  
Xuyang Chen ◽  
...  

Objective: To explore the inhibitory and synergistic effects of 5-fluorouracil and curcumin on Hep-2 laryngeal cancer cells and clarify the effect of mesoporous silica nanoparticles as drug carriers. Methods: The inhibitory effects of 5-fluorouracil and curcumin on Hep-2 cells were detected using the CCK-8 assay. CompuSyn was used to calculate the synergistic effect of the 2 drugs. Flow cytometry was used to detect apoptosis and cell cycle arrest induced by 5-fluorouracil and curcumin. The drugs were loaded into mesoporous nanoparticles. Western blotting was used to detect the expression of related proteins after treatment. The growth of subcutaneous tumors in BALB/c nude after the intraperitoneal injection with drug-loaded mesoporous silica nanoparticles was recorded. Results: 5-Fluorouracil and curcumin synergistically induced apoptosis and cell cycle arrest in Hep-2 cells. Mesoporous silica nanoparticles as drug carriers enhanced the therapeutic effects of 5-fluorouracil and curcumin. Conclusions: Mesoporous silica nanoparticles are expected to be effective drug carriers that enhance the synergistic effects of 5-fluorouracil and curcumin on laryngeal cancer.


RSC Advances ◽  
2020 ◽  
Vol 10 (52) ◽  
pp. 31463-31469
Author(s):  
Xiaoming Fang ◽  
Yanhua Huang ◽  
Dan Yu ◽  
Caiwen Shi ◽  
Ming Liu

Folic acid functionalized CuNCs@SiO2 nanocomposites with superior fluorescence properties, high stability and good biocompatibility for targeted cell imaging.


2020 ◽  
Author(s):  
Chang Liu ◽  
Xiaoyu Xu ◽  
Junnian Zhou ◽  
Jiaqi Yan ◽  
Dongqing Wang ◽  
...  

Abstract Metal-organic frameworks (MOFs) have proven to be a promising class of drug carriers due to their high porosity, crystalline properties with defined structure information, and their potential for further functionalization. However, to date, no extensive research has been conducted on MOF-based drug carriers with stimuli-responsive, dual-drug delivery, and tumor targeting functions. Here, we demonstrate the strategy of constructing a redox responsive and tumor-targeted MOF, as dual-drug carrier, by anchoring functional disulfide anhydride and folic acid (FA) molecules to the organic links of MOFs, respectively. The MOF composites show the controlled release of loaded 5-fluorouracil (5-FU) entrapped within UiO-66-NH2 nanostructures modified by dichloroacetic acid (DCA). Moreover, the MOF building block DCA acts as a synergistical drug to 5-FU in cancer cells inhibition. Through disulfide bonds, the gated MOF has redox-responsive drugs release. The confocal laser scanning microscopy further proved that conjugation of folic acid to the MOF surface can significantly enhance the targeting ability to cancer cells and the cancer cell uptake of FA-MOFs. The synthesis of redox-responsive dual-drug delivery MOF hybrids paves the way to assemble of other MOF hybrids that respond to other triggering factors such as light, temperature, pH, or biomarkers. The properties and functions of such materials are expected to influence the development of sensors, new catalysts, photonic devices, and drug delivery carriers.


2016 ◽  
Vol 4 (25) ◽  
pp. 4382-4388 ◽  
Author(s):  
Xin Chen ◽  
Zhongning Liu

Dual responsive mesoporous silica nanoparticles integrating stepwise tumor targeting and co-delivery of multiple anticancer drugs were developed to attenuate the drug resistance of cancer cells.


Materials ◽  
2021 ◽  
Vol 14 (12) ◽  
pp. 3226
Author(s):  
Gun Gyun Kim ◽  
Hye Min Jang ◽  
Sung Bum Park ◽  
Jae-Seon So ◽  
Sang Wook Kim

This study evaluated the in vivo behavior and accumulation of silica particles in the form of wires, which were actively studied as drug carriers along with spheres, using positron emission tomography (PET). Wire-shaped silicon dioxide (SiO2) was synthesized at micro-size, using anodic aluminum oxide (AAO), a template, and folic acid (FA), which specifically binds folate receptors (FR) which are overexpressed in many cancers, and which was bound to the wire’s surface to confirm its possible use as a cancer diagnostic agent. In addition, for evaluation using PET, the positron-emitting nuclide 89Zr (t1/2 = 3.3 days) was directly bonded to the hydroxyl group (-OH) on the particle surface. The diameter and shape of the synthesized silica microwires (SMWs) were confirmed using SEM and TEM, the chemical bonding of FA was confirmed through FT–IR and NMR, and the labeling of 89Zr was measured by means of radio-thin-layer chromatography (TLC) measurement. Folic acid-conjugated SMWs (FA-SMWs) were found to have a low receptor-mediated uptake in cell internalization evaluation, but in PET studies, FA-SMWs stayed longer at the tumor site. In conclusion, we successfully synthesized a homogeneous silica microwire for drug delivery, we confirmed that the FA-conjugated sample remains at the tumor site for a relatively longer time, and we have reported the characteristic in vivo behavior of 89Zr-FA-SMWs.


2012 ◽  
Vol 42 (8) ◽  
pp. 1172-1178
Author(s):  
Jun YUE ◽  
Rui WANG ◽  
XiuLi HU ◽  
XiaBin JING ◽  
Shi LIU

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