ABSTRACT
We describe a calcium carbonate (CaCO3) mineralization approach to generate pH-responsive nanocarriers that can stably load S-nitrosoglutathione (GSNO) and dissolve at acidic endosomes to trigger intracellular release of nitric oxide (NO). GSNO-loaded CaCO3-mineralized nanoparticles (GSNO-MNPs) were prepared by an anionic block copolymer (PEG-Poly(l-aspartic acid))-templated mineralization. Ionic GSNO could be loaded in situ inside the CaCO3 core during the mineralization process. The stability of GSNO shielded within the crystalline CaCO3 core was greatly enhanced. The GSNO-MNPs triggered NO release at endosomal pH and an intracellular ascorbic acid level. Confocal microscopy demonstrated that the GSNO-MNPs could be dissolved at endosomal environments to release GSNO and sequentially generate NO through the GSNO reduction in the cytosol. In vitro cell experiments demonstrated that NO release by the GSNO-MNPs efficiently improved therapeutic activity of doxorubicin (DOX).
Subject(s)
Calcium Carbonate/chemistry , Doxorubicin/pharmacology , Drug Carriers/chemistry , Nanoparticles/chemistry , Nitric Oxide/metabolism , Polymers/chemistry , S-Nitrosoglutathione/chemistry , Antibiotics, Antineoplastic/chemistry , Antibiotics, Antineoplastic/pharmacology , Cell Survival/drug effects , Cytoplasm/metabolism , Doxorubicin/administration & dosage , Humans , Hydrogen-Ion Concentration , MCF-7 CellsABSTRACT
We report on pH-responsive core-shell polymer micelles with catechol-Fe(3+) coordinated core cross-links, which provide robustness to drug-loaded polymer micelles and allow the facilitated intracellular release of loaded anticancer drugs in response to an endosomal acidic pH.
Subject(s)
Ferric Compounds/chemistry , Micelles , Polymers/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Catechols/chemistry , Cell Proliferation/drug effects , Doxorubicin/chemistry , Doxorubicin/pharmacology , Drug Carriers/chemistry , Humans , Hydrogen-Ion Concentration , Ligands , MCF-7 CellsABSTRACT
A titanium (Ti)-adhesive nanoparticle is developed as a surface-releasing system for dual osteogenic growth factors. The Ti-adhesive nanoparticle is prepared by self-assembly of a poly(L-lactide-co-glycolide) (PLGA)-grafted hyaluronic acid (HA) copolymer, followed by conjugation of catechol groups on nanoparticle surfaces. The nanoparticles consist of Ti-adhesive peripheral catechol groups, anionic HA shells, and hydrophobic PLGA inner cores. The immobilization of the nanoparticles onto Ti substrates is successfully verified using various analytical tools including field-emission scanning electron microscopy (Fe-SEM), contact angle measurement, and X-ray photoelectron spectroscopy (XPS). Positively charged dual growth factors, bone morphogenetic protein-2 (BMP-2) and insulin-like growth factor-1 (IGF-1) are readily loaded onto the negatively charged HA shells of surface-immobilized nanoparticles, which is confirmed by fluorescence microscopy. The Ti substrates with dual growth factor-loaded nanoparticle-immobilized nanoparticles remarkably promote the attachment, proliferation, spreading, and alkaline phosphatase (ALP) activity of human adipose-derived stem cells (hADSCs).
