Surface bioengineering of diatomite based nanovectors for efficient intracellular uptake and drug delivery.

Abstract

Diatomite is a natural porous silica material of sedimentary origin. Due to its peculiar properties, it can be considered as a valid surrogate of synthetic porous silica for nano-based drug delivery. In this work, we exploit the potential of diatomite nanoparticles (DNPs) for drug delivery with the aim of developing a successful dual-biofunctionalization method by polyethylene glycol (PEG) coverage and cell-penetrating peptide (CPP) bioconjugation, to improve the physicochemical and biological properties of the particles, to enhance the intracellular uptake in cancer cells, and to increase the biocompatibility of 3-aminopropyltriethoxysilane (APT) modified-DNPs. DNPs-APT-PEG-CPP showed hemocompatibility for up to 200 μg mL(-1) after 48 h of incubation with erythrocytes, with a hemolysis value of only 1.3%. The cytotoxicity of the modified-DNPs with a concentration up to 200 μg mL(-1) and incubation with MCF-7 and MDA-MB-231 breast cancer cells for 24 h, demonstrated that PEGylation and CPP-bioconjugation can strongly reduce the cytotoxicity of DNPs-APT. The cellular uptake of the modified-DNPs was also evaluated using the above mentioned cancer cell lines, showing that the CPP-bioconjugation can considerably increase the DNP cellular uptake. Moreover, the dual surface modification of DNPs improved both the loading of a poorly water-soluble anticancer drug, sorafenib, with a loading degree up to 22 wt%, and also enhanced the drug release profiles in aqueous solutions. Overall, this work demonstrates that the biofunctionalization of DNPs is a promising platform for drug delivery applications in cancer therapy as a result of its enhanced stability, biocompatibility, cellular uptake, and drug release profiles.

• Authors: Monica Terracciano, Mohammad-Ali Shahbazi, Alexandra Correia, Ilaria Rea, Annalisa Lamberti, Luca De Stefano, Hélder A Santos
• Journal: Nanoscale (Nanoscale) Vol. 7 Issue 47 Pg. 20063-74 (Dec 21 2015) ISSN: 2040-3372 [Electronic] England
• PMID: 26568517 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Biocompatible Materials
• Cell-Penetrating Peptides
• Drug Carriers
• Phenylurea Compounds
• Propylamines
• Silanes
• Water
• Niacinamide
• Polyethylene Glycols
• Diatomaceous Earth
• diatomite
• Sorafenib
• amino-propyl-triethoxysilane

Topics

• Antineoplastic Agents (chemistry)
• Biocompatible Materials (chemistry)
• Cell Line, Tumor
• Cell Survival
• Cell-Penetrating Peptides (chemistry)
• Diatomaceous Earth (chemistry)
• Drug Carriers (chemistry)
• Drug Delivery Systems
• Erythrocytes (cytology)
• Hemolysis
• Humans
• Hydrogen-Ion Concentration
• MCF-7 Cells
• Microscopy, Confocal
• Microscopy, Electron, Scanning
• Microscopy, Electron, Transmission
• Nanoparticles (chemistry)
• Niacinamide (analogs & derivatives, therapeutic use)
• Phenylurea Compounds (therapeutic use)
• Polyethylene Glycols (chemistry)
• Propylamines
• Silanes (chemistry)
• Solubility
• Sorafenib
• Spectroscopy, Fourier Transform Infrared
• Water (chemistry)