scholarly journals Drug Delivery: Enzyme-Responsive Cell-Penetrating Peptide Conjugated Mesoporous Silica Quantum Dot Nanocarriers for Controlled Release of Nucleus-Targeted Drug Molecules and Real-Time Intracellular Fluorescence Imaging of Tumor Cells (Adv. Healthcare Mate

2014 ◽  
Vol 3 (8) ◽  
pp. 1121-1121 ◽  
Author(s):  
Jinming Li ◽  
Fang Liu ◽  
Qing Shao ◽  
Yuanzeng Min ◽  
Marianne Costa ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Controlled Release ◽  
Mesoporous Silica ◽  
Tumor Cells ◽  
Cell Penetrating Peptide ◽  
Drug Molecules ◽  
Cell Penetrating ◽  
Targeted Drug ◽  
Intracellular Fluorescence ◽  
Responsive Cell

Design of a new pH‐activatable cell‐penetrating peptide for drug delivery into tumor cells

2019 ◽  
Vol 94 (5) ◽  
pp. 1884-1893 ◽  
Author(s):  
Yun Zhang ◽  
Li Li ◽  
Linlin Chang ◽  
Hui Liu ◽  
Jingjing Song ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Tumor Cells ◽  
Cell Penetrating Peptide ◽  
Cell Penetrating

scholarly journals Galactosylated Chitosan-Functionalized Mesoporous Silica Nanoparticle Loading by Calcium Leucovorin for Colon Cancer Cell-Targeted Drug Delivery

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3082 ◽  
Author(s):  
Wei Liu ◽  
Fan Wang ◽  
Yongchao Zhu ◽  
Xue Li ◽  
Xiaojing Liu ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Colon Cancer ◽  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Tumor Cells ◽  
Targeted Drug Delivery ◽  
Mesoporous Silica Nanoparticles ◽  
Drug Loading ◽  
Targeted Drug ◽  
Galactosylated Chitosan

Targeted drug delivery to colon cancer cells can significantly improve the efficiency of treatment. We firstly synthesized carboxyl-modified mesoporous silica nanoparticles (MSN–COOH) via two-step synthesis, and then developed calcium leucovorin (LV)-loaded carboxyl-modified mesoporous silica nanoparticles based on galactosylated chitosan (GC), which are galectin receptor-mediated materials for colon-specific drug delivery systems. Both unmodified and functionalized nanoparticles were characterized by scanning electron microscopy (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD), Fourier transform infrared (FT-IR), nitrogen sorption, and dynamic light scattering (DLS). Drug release properties and drug loading capacity were determined by ultraviolet spectrophotometry (UV). LV@MSN–COOH/GC had a high LV loading and a drug loading of 18.07%. In vitro, its release, mainly by diffusion, was sustained release. Cell experiments showed that in SW620 cells with the galectin receptor, the LV@MSN–COOH/GC metabolized into methyl tetrahydrofolic acid (MTHF) and 5-fluorouracil (5-FU)@MSN–NH2/GC metabolized into FdUMP in vivo. MTHF and 5-fluoro-2′-deoxyuridine 5′-monophosphate (FdUMP) had combined inhibition and significantly downregulated the expression of thymidylate synthase (TS). Fluorescence microscopy and flow cytometry experiments show that MSN–COOH/GC has tumor cell targeting, which specifically recognizes and binds to the galectin receptor in tumor cells. The results show that the nano-dosing system based on GC can increase the concentrations of LV and 5-FU tumor cells and enhance their combined effect against colon cancer.

Activable Cell-Penetrating Peptide Conjugated Prodrug for Tumor Targeted Drug Delivery

2015 ◽  
Vol 7 (29) ◽  
pp. 16061-16069 ◽  
Author(s):  
Hong Cheng ◽  
Jing-Yi Zhu ◽  
Xiao-Ding Xu ◽  
Wen-Xiu Qiu ◽  
Qi Lei ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Drug Delivery ◽  
Cell Penetrating Peptide ◽  
Cell Penetrating ◽  
Targeted Drug

scholarly journals Dimerization of a cell-penetrating peptide leads to enhanced cellular uptake and drug delivery

2012 ◽  
Vol 8 ◽  
pp. 1788-1797 ◽  
Author(s):  
Jan Hoyer ◽  
Ulrich Schatzschneider ◽  
Michaela Schulz-Siegmund ◽  
Ines Neundorf
Keyword(s):  
Drug Delivery ◽  
Tumor Cells ◽  
Cell Lines ◽  
Cellular Uptake ◽  
Cell Penetrating Peptides ◽  
Antimicrobial Protein ◽  
Cell Penetrating Peptide ◽  
Specific Cell ◽  
Cell Penetrating ◽  
A Cell

Over the past 20 years, cell-penetrating peptides (CPPs) have gained tremendous interest due to their ability to deliver a variety of therapeutically active molecules that would otherwise be unable to cross the cellular membrane due to their size or hydrophilicity. Recently, we reported on the identification of a novel CPP, sC18, which is derived from the C-terminus of the 18 kDa cationic antimicrobial protein. Furthermore, we demonstrated successful application of sC18 for the delivery of functionalized cyclopentadienyl manganese tricarbonyl (cymantrene) complexes to tumor cell lines, inducing high cellular toxicity. In order to increase the potential of the organometallic complexes to kill tumor cells, we were looking for a way to enhance cellular uptake. Therefore, we designed a branched dimeric variant of sC18, (sC18)2, which was shown to have a dramatically improved capacity to internalize into various cell lines, even primary cells, using flow cytometry and fluorescence microscopy. Cell viability assays indicated increased cytotoxicity of the dimer presumably caused by membrane leakage; however, this effect turned out to be dependent on the specific cell type. Finally, we could show that conjugation of a functionalized cymantrene with (sC18)2leads to significant reduction of its IC50value in tumor cells compared to the respective sC18 conjugate, proving that dimerization is a useful method to increase the drug-delivery potential of a cell-penetrating peptide.

scholarly journals ADAM9-Responsive Mesoporous Silica Nanoparticles for Targeted Drug Delivery in Pancreatic Cancer

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3321
Author(s):  
Etienne J. Slapak ◽  
Lily Kong ◽  
Mouad el Mandili ◽  
Rienk Nieuwland ◽  
Alexander Kros ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Conditioned Medium ◽  
Drug Delivery System ◽  
Delivery System ◽  
Targeted Drug Delivery ◽  
Mesoporous Silica Nanoparticles ◽  
Pdac Cell ◽  
Targeted Drug

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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