title: Retinol encapsulated into amorphous Ca(2+) polyphosphate nanospheres acts synergistically in MC3T3-E1 cells.
abstract: Both the quality and quantity of collagen, the major structural component of the skin, decrease in aging skin. We succeeded to encapsulate retinol into amorphous inorganic polyphosphate (polyP) nanoparticles together with calcium ions ("aCa-polyP-NP"), under formation of amorphous Ca-polyP/retinol nanospheres ("retinol/aCa-polyP-NS"). The globular nanospheres are not cytotoxic, show an almost uniform size of ≈ 45 nm and have a retinol content of around 25%. Both components of those nanospheres, retinol and the aCa-polyP-NP, if administered together, caused a strong increase in proliferation of mouse calvaria MC3T3 cells. The expressions of collagen types I, II and III genes, but not the expression of collagen type V gene, were significantly enhanced if retinol is added together with aCa-polyP-NP. This synergistic effect was especially pronounced for the expression of the collagen type III gene. We propose that the synergistic effect of the retinol/aCa-polyP-NS on cell growth and collagen type III expression is induced via two routes, first through cellular uptake of the 45 nm nanospheres by clathrin-mediated endocytosis and second through extracellular disintegration of the nanospheres resulting in the release of retinol which is then taken up into the cells after binding to the retinal binding protein receptor.
authors.affiliation: ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany. Electronic address: wmueller@uni-mainz.de.
authors.forename: Werner E G
authors.initials: WE
authors.lastname: Müller
authors.affiliation: ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany; Biomaterials Department, Inorganic Chemical Industries Division, National Research Center, Doki, 11884 Cairo, Egypt.
authors.forename: Emad
authors.initials: E
authors.lastname: Tolba
authors.affiliation: ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany.
authors.forename: Heinz C
authors.initials: HC
authors.lastname: Schröder
authors.affiliation: NanotecMARIN GmbH, Duesbergweg 6, D-55128 Mainz, Germany.
authors.forename: Bärbel
authors.initials: B
authors.lastname: Diehl-Seifert
authors.affiliation: ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany. Electronic address: wang013@uni-mainz.de.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wang
mesh_terms: D016475:3T3 Cells; D000818:Animals; D017610:Calcium Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004357:Drug Synergism; D004705:Endocytosis / Q000187:drug effects; D051379:Mice; D050997:Nanomedicine; D054118:Nanospheres; D010316:Particle Size; D011122:Polyphosphates / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D012177:Retinol-Binding Proteins / Q000378:metabolism; D012886:Skull / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013678:Technology, Pharmaceutical / Q000379:methods; D015854:Up-Regulation; D014801:Vitamin A / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D017610:Calcium Compounds; D024042:Collagen Type I; D024043:Collagen Type II; D024061:Collagen Type III; D004337:Drug Carriers; D011122:Polyphosphates; D012177:Retinol-Binding Proteins; D014801:Vitamin A
keywords: Collagen type III; Polyphosphate; Retinol; Skin damage; Synergistic action