ABSTRACT
Functional polymeric drug delivery systems have generated enormous interest due to their excellent features. This paper reports the development of a novel pH and redox dual-sensitive polymer for anticancer paclitaxel (PTX) delivery applications. The polymer was prepared by polycondensation of disulfide bond-containing dimethyl l-cystinate (Cys) and polycaprolactone (PCL) oligomer via a pH-responsive imine bond. Using the nanoprecipitation method, the polymer can be formulated as nanoparticles (poly(Cys-PCL)/PTX NPs) with a diameter less than 100 nm, as measured by TEM and DLS. The NPs release PTX significantly faster at mildly acidic pH and high concentrations of GSH, exhibiting almost no burst release under the physiological conditions of plasma. Notably, the NPs efficiently deliver PTX to the tumor cells, which was more cytotoxic to 4T1 cancer cells than the pure PTX alone. In vivo results reveal an excellent tumor inhibiting ability, good drug tolerability and biosafety of poly(Cys-PCL)/PTX NPs. Overall, the poly(Cys-PCL)/PTX NPs platform may have greater potential in enhancing cancer therapy.
Subject(s)
Antineoplastic Agents/chemistry , Drug Carriers/chemistry , Nanoparticles/chemistry , Paclitaxel/chemistry , Polymers/chemistry , Animals , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacology , Biological Transport , Cell Line, Tumor , Drug Carriers/pharmacokinetics , Drug Liberation , Intracellular Space/metabolism , Male , Mice , Paclitaxel/metabolism , Paclitaxel/pharmacology , Particle Size , Polymers/pharmacokinetics , Rats , Rats, Sprague-Dawley , Tissue DistributionABSTRACT
Perihilar cholangiocarcinoma (PHCC) is one of the most aggressive and complex types of cancer with a poor survival. Despite advances in PHCC diagnosis and treatment, the biology of this tumor remains poorly understood. Recent studies have suggested long non-coding RNAs (lncRNAs) as crucial determinants of cancer progression. However, the role of lncRNAs in PHCC is rarely reported and the function of gastric adenocarcinoma predictive long intergenic non-coding RNA (GAPLINC) in PHCC has yet to be elucidated. The present study observed a significant upregulation of GAPLINC in PHCC cell lines and clinical specimens (P<0.05). Furthermore, by comparing clinicopathological characteristics with expression data, high GAPLINC expression was revealed to be associated with the T stage (P=0.013), N stage (P<0.001) and Tumor-Node-Metastasis stage (P<0.001) of PHCC. Furthermore, Kaplan-Meier analysis demonstrated that GAPLINC expression was associated with poor overall survival and progression-free survival rates in PHCC. Furthermore, univariate and multivariate COX regression analyses identified high GAPLINC expression as a risk factor of a poor prognosis in PHCC. GAPLINC upregulation promoted the migration and invasion of PHCC cells in Transwell and Matrigel assays, respectively, while GAPLINC deficiency inhibited PHCC cell metastasis. Furthermore, PHCC cells with GAPLINC overexpression exhibited markedly increased proliferation ability in a Cell Counting kit-8 assay. However, GAPLINC interference significantly suppressed cell proliferation. In conclusion, GAPLINC may promote PHCC progression and may serve as a potential prognostic marker and therapeutic target of PHCC.
ABSTRACT
An electrochemical sensor of acetaminophen (AP) based on electrochemically reduced graphene (ERG) loaded nickel oxides (Ni2O3-NiO) nanoparticles coated onto glassy carbon electrode (ERG/Ni2O3-NiO/GCE) was prepared by a one-step electrodeposition process. The as-prepared electrode was characterized by scanning electron microscopy, X-ray photoelectron spectroscopy and Raman spectroscopy. The electrocatalytic properties of ERG/Ni2O3-NiO modified glassy carbon electrode toward the oxidation of acetaminophen were analyzed via cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The electrodes of Ni2O3-NiO/GCE, ERG/GCE, and Ni2O3-NiO deposited ERG/GCE were fabricated for the comparison and the catalytic mechanism understanding. The studies showed that the one-step prepared ERG/Ni2O3-NiO/GCE displayed the highest electro-catalytic activity, attributing to the synergetic effect derived from the unique composite structure and physical properties of nickel oxides nanoparticles and graphene. The low detection limit of 0.02 µM (S/N=3) with the wide linear detection range from 0.04 µM to 100 µM (R=0.998) was obtained. The resulting sensor was successfully used to detect acetaminophen in commercial pharmaceutical tablets and urine samples.
