RESUMO
5-Fluorouracil (5-FU) is a chemotherapeutic drug against many types of cancers, especially colorectal cancer. However, its short plasma half-life and serious adverse reactions limit its wide clinical applications. To overcome these shortcomings, a novel lipophilic 5-FU carbonate [XL-01, (5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl) methyl tetradecyl carbonate] was designed, synthesized, and encapsulated into liposome (LipoXL-01) by a thin-film dispersion method through formulation screening and optimization. LipoXL-01 was characterized by a particle size of around 100 nm, polydispersity index of 0.200, ζ-potential value of -41 mV, encapsulation efficiency of 93.9%, and drug-loading efficiency of 11.6%. The cellular uptake of LipoXL-01 was increased in a concentration-dependent manner on HCT15 cells. LipoXL-01 could enhance the induction of cell apoptosis and the inhibition of cell migration and arrest the ability of the cell cycle at the S-phase on HCT15 cells better than 5-FU. Additionally, LipoXL-01 exhibited a slow drug release profile with a cumulative release rate of 12% in 8 h. The results of pharmacokinetic and biodistribution studies revealed that LipoXL-01 had a long plasma half-life (7.21 h) and a high tumor accumulation (733 nmol/g at 8 h). The in vivo antitumor effect study also showed that LipoXL-01 had more potent efficacy than 5-FU (65 vs 48% of the tumor-inhibition rate). Simultaneously, negligible systemic toxicity was observed via analyzing the body weight as well as hematological and pathological parameters in the tested mice. The current study suggested that LipoXL-01 might be a promising nanocandidate for chemotherapy of colorectal cancer.
Assuntos
Antineoplásicos , Neoplasias Colorretais , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carbonatos , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Fluoruracila/uso terapêutico , Lipossomos/uso terapêutico , Camundongos , Distribuição TecidualRESUMO
Gemcitabine (GEM) is a non-selective chemotherapeutic agent used in the treatment of pancreatic cancer. Its antitumor efficacy is limited by a short plasma half-life and severe adverse reactions. To overcome these shortcomings, four novel lipid-like GEM diesters were synthesized and encapsulated into liposomes. Through optimization, dimyristoyl GEM (dmGEM)-loaded liposomes (LipodmGEM) were successfully obtained with an almost complete encapsulation efficiency. Compared to free GEM, LipodmGEM showed enhanced cellular uptake and cell apoptosis, improved inhibition of cell migration on AsPC-1 cells and a greatly extended half-life (7.22 vs. 1.78 h). LipodmGEM succeeded in enriching the drug in the tumor (5.28 vs. 0.03 µmol/g at 8 h), overcoming a major shortcoming of GEM, showed excellent anticancer efficacy in vivo and negligible systemic toxicity, superior to GEM. Attractive as well, suspensions of LipodmGEM remained stable at 2-10 °C away from light for no <2 years. Our results suggest that LipodmGEM might become of high interest for treating pancreatic cancer while the simple strategy we reported might be explored as well for converting other antitumor drugs with high water-solubility and short plasma half-life into attractive nanomedicines.
Assuntos
Gencitabina , Neoplasias Pancreáticas , Humanos , Lipossomos/uso terapêutico , Desoxicitidina/uso terapêutico , Desoxicitidina/farmacologia , Linhagem Celular Tumoral , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Lipídeos/uso terapêuticoRESUMO
Green electromagnetic interference (EMI) shielding materials not only require high shielding effectiveness (SE) and low reflection but also need to be recyclable after damage; however, it is challenging to strike a balance in practice. Here, a polyacrylamide (PAM) composite composed of numerous chemically cross-linked PAM@carbon nanotube (cPAM@CNT) core-shell particles featuring rich wrinkled microstructures was prepared using an adsorption-drying-shrinking strategy. The wrinkled microstructures enable the incident electromagnetic waves (EMWs) to undergo attenuation within the composites, achieving an average EMI SE of 67.5 dB in the X band. Due to the hygroscopicity of hydrophobically associated PAM (hPAM, an adhesive for cPAM@CNTs core-shell particles), the average EMI SE of the composites further increased to 83.2 dB after exposure to 91% relative humidity for 24 h, with only a 2.7 dB low reflection. Additionally, the composites also demonstrated excellent Joule heating, photothermal performance, and recyclability, which exhibit substantial promise for advanced EMI shielding applications.
RESUMO
The influence of the bending radius on the sensitivity of the graphene quantum dots (GQDs)-coated probe is experimentally investigated for a U-shaped probe. The fiber is bent into a U shape using the optic fiber flame heating method, and the optic fiber is enclosed in a glass tube to increase the stability of the probe. The surface of the U-shaped optical fiber was coated with electrospun fibers formed via electrospinning. Polymer materials doped with GQDs are applied to U-shaped optical fiber as humidity sensors. Graphene quantum dot nanofibers on the U-shaped optical fiber sensor to form a network structure of graphene quantum dots U-shape fiber sensor (GQDUS). The polymer network structure absorbs water molecules, which in turn affects the bending radius of the optical fiber, and changes the optical fiber spectrum. Graphene quantum dots provide optical enhancement benefits, which in turn increase the sensitivity of fiber optic sensors. The spectra monitoring system consists of an optical spectrum analyzer (OSA) and an amplified spontaneous emission (ASE). This system can be used to detect humidity changes between 20% RH and 80% RH in the chamber. Our results indicate promising applications for quantum dots probe sensors from electrospun nanofibers increasing sensitive environmental monitoring. As such, it could be of substantial value in optical sensors detection.
RESUMO
Pancreatic cancer is an aggressive and highly lethal disease with a very poor prognosis. Our previous study found miriplatin can inhibit proliferation of various tumor cells, including pancreatic cancer cells. For the chemotherapy of pancreatic cancer, a novel recombinant human serum albumin (rHSA)-bound miriplatin nanoparticles (rHSA-miPt) were constructed by emulsion-diffusion evaporation method. The optimal formulation was composed of 150 mg of rHSA and 30 mg of miriplatin. The key parameters in rHSA-miPt production were 10 min of high-pressure homogenization in a solution with volume ratio of 10:2 of 5% glucose and chloroform. The rHSA-miPt was characterized with a particle size of 61 ± 10 nm, a zeta potential value of -18 ± 5 mV, encapsulation efficiency of 98.4%, drug loading of 16.4%, T1/2 of 13.3 h and Vd of 0.5 L in Sprague Dawley rats. The concentrations of platinum (Pt) in the tumors were 15 and 22-fold higher than those in the blood at 24 and 72 h in tumor-bearing mice, respectively. The internalization of rHSA-miPt through caveolae-dependent pathway. In vitro, the half-maximal inhibitory concentration (IC50) of rHSA-miPt was 12.7 µM vs more than 100 µM of gemcitabine (Gem). The inhibition rate of tumor growth was 76% of rHSA-miPt and 51% of Gem, respectively. Compared with Gem, rHSA-miPt was identified to be safer and less toxic based on body weight loss in mice (0% vs 20%), the survival rate of mice (100% vs 80%) and hematological and biochemical parameters of the mice including leukocytes, lymphocytes, neutrophils, monocytes, serum alanine aminotransferase and aspartate aminotransferase. The present study revealed that rHSA-miPt might be a promising candidate for pancreatic cancer therapy.