title: 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.affiliation: Institute for Microelectronics and Microsystems, National Research Council, Naples, 80131, Italy. luca.destefano@na.imm.cnr.it.
authors.forename: Monica
authors.initials: M
authors.lastname: Terracciano
authors.forename: Mohammad-Ali
authors.initials: MA
authors.lastname: Shahbazi
authors.forename: Alexandra
authors.initials: A
authors.lastname: Correia
authors.forename: Ilaria
authors.initials: I
authors.lastname: Rea
authors.forename: Annalisa
authors.initials: A
authors.lastname: Lamberti
authors.forename: Luca
authors.initials: L
authors.lastname: De Stefano
authors.forename: Hélder A
authors.initials: HA
authors.lastname: Santos
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry; D001672:Biocompatible Materials / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival; D057846:Cell-Penetrating Peptides / Q000737:chemistry*; D007692:Diatomaceous Earth / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004912:Erythrocytes / Q000166:cytology; D006461:Hemolysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D061986:MCF-7 Cells; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000737:chemistry; D011437:Propylamines; D012821:Silanes / Q000737:chemistry; D012995:Solubility; D000077157:Sorafenib; D017550:Spectroscopy, Fourier Transform Infrared; D014867:Water / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D010671:Phenylurea Compounds; D011437:Propylamines; D012821:Silanes; D014867:Water; D009536:Niacinamide; D011092:Polyethylene Glycols; D007692:Diatomaceous Earth; C033787:diatomite; D000077157:Sorafenib; C477625:amino-propyl-triethoxysilane