ABSTRACT
Ru or Pt nanoparticles have been prepared following the organometallic approach and deposited onto the surface of mesoporous graphitic carbon nitride (mpg-CN). Three different Ru-based samples have also been compared to investigate the effect of 4-phenylpyridine as a stabilizing agent. The photocatalytic performance towards the hydrogen evolution reaction (HER) has been tested showing that all hybrid systems clearly outperform the photocatalytic activity of bare mpg-CN. In particular, Pt-decorated mpg-CN yields the largest H2 production upon visible-light irradiation (870 µmol h-1 g-1, TOF = 14.1 h-1, TON = 339 after 24 h) when compared with the Ru-based samples (137-155 µmol h-1 g-1, TOFs between 2.3-2.7 h-1, TONs between 54-57 after 24 h). Long-term photochemical tests (up to 65 h irradiation) show also an improved stability of the Pt-based samples over the Ru counterpart. Photophysical experiments aimed at rationalizing the photocatalytic performance of the different hybrid systems elucidate that the enhanced activity of the Pt-decorated mpg-CN over the Ru-based analogues arises from improved electron transfer kinetics from mpg-CN to the metal nanoparticles.
ABSTRACT
Conventional chemotherapy, because of the high dose to keep the drug above the minimum effective concentration, possesses severe side effects and brings extra pain to patients. A controlled release drug delivery system, which is a bilayer self-assembled nanoparticle (NP) in this study, can solve this problem. Zein, a biodegradable natural protein from corn, was selected for the first layer of the drug encapsulation. The second layer was formed via the reversible ionic hydrogen bonds between zein and folic acid (FA), which was selected because of the two carboxylic acids and one amine group in its simple structure. Doxorubicin (DOX), a popular anticancer drug, was selected as the drug model to form the bilayer drug nanoencapsulation FA-NP-DOX. The in vitro controlled release profile of FA-NP-DOX was obtained. The in vivo pharmacokinetics and anticancer activity of FA-NP-DOX in tumor-xenografted animal models were also conducted. Compared to the zein nanoencapsulation of DOX (NP-DOX) and pure DOX, FA-NP-DOX showed comparable in vitro cytotoxicity but much longer in vitro controlled release time and in vivo circulation time. Both FA-NP-DOX and NP-DOX showed enhanced therapeutical efficiency in vivo than pure DOX. It is concluded that the bilayer self-assembled NP of zein and FA highly prolonged the controlled release and enhanced the therapeutic efficiency of the anticancer drug.
Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Antibiotics, Antineoplastic/pharmacology , Doxorubicin/administration & dosage , Doxorubicin/pharmacology , Drug Carriers/chemistry , Lipid Bilayers/chemistry , Nanoparticles/chemistry , Zein/chemistry , Animals , Antibiotics, Antineoplastic/chemistry , Cell Proliferation/drug effects , Disease Models, Animal , Doxorubicin/chemistry , Drug Liberation , Drug Screening Assays, Antitumor , HeLa Cells , Humans , Hydrogen-Ion Concentration , Mice , Mice, Inbred BALB C , Mice, Nude , Molecular Structure , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/pathology , Particle Size , Surface PropertiesABSTRACT
Prodrug, in which the inactive parent drug with good bioavailability is metabolized into an active drug in the body, is one of the main strategies to target the disease site to improve the drug efficiency and reduce the adverse effects of chemotherapy. Because of the good capability of chemical modification, zein, a plant derived protein, and drugs can be conjugated through environmentally sensitive links to form prodrugs capable of triggered drug release. In this study, a novel prodrug was synthesized using paclitaxel (PTX), zein, and a disulfide linker, and nanoparticles were formed by self-assembly of the prodrug. An effective in vitro triggered release, 80-90% in 5 min, of the prodrug based nanoparticles (zein-S-S-PTX_NP) was successfully approached. The cytotoxicity of zein-S-S-PTX_NP as well as the zein encapsulation of PTX (zein_PTX_NP) and pure PTX on HeLa cells and NIH/3T3 fibroblast cells was tested using MTS assay. It showed that, after the treatment of zein-S-S-PTX_NP at the equivalent PTX concentrations of 0.1, 0.5, 1, and 5 µg/mL, respectively, zein-S-S-PTX_NP had zero damage to normal cells but a similar cytotoxicity to cancer cells as pure PTX. In the animal study, the tumor was 50% of the original size after the treatment of zein-S-S-PTX_NP for 9 days with 3 doses. This study suggested that the novel prodrug based nanoparticle zein-S-S-PTX_NP could be a promising approach in chemotherapy with targeted delivery, improved efficacy, and reduced side effects.
