Search

In postgraphene two-dimensional materials (2DMs), MoS

The aims of this study were to reveal the usefulness of a newly developed method for measuring tongue volume (TV) and oral cavity capacity (OCC) and to assess the relationship between them. The tongue was coated with a contrast agent, and the TV and OCC were determined using cone-beam computed tomography (CBCT). We enrolled 20 adults who were scheduled to undergo CBCT to evaluate the relationship of the third molar roots to the alveolar nerve before molar extraction. Each participant’s tongue was coated with a contrast agent, and CBCT of the tongue and oral cavity was performed. Using computer software, we evaluated reconstructed 3D images of the TV, oral cavity proper volume (OCPV), and OCC. The mean TV was 47.07 ± 7.08 cm3. The mean OCPV and OCC were 4.40 ± 2.78 cm3 and 51.47 ± 6.46 cm3, respectively. There was a significant correlation between TV and OCC (r = 0.920; p

In postgraphene two-dimensional materials (2DMs), MoS2 has attracted increasing attention in the biomedical field due to its excellent physicochemical properties. However, the toxicity and biocompatibility evaluation of MoS2 is not fully addressed. Herein, chitosan functionalized MoS2 (CS-MoS2) nanosheets, which showed perfect dispersibility and stability performances, were synthesized and characterized. We found that CS-MoS2 nanosheets inhibited the viability of human dermal fibroblasts (HDFs) moderately while causing cell membrane instability, ROS generation, and DNA damage in a dosage-dependent manner. CS-MoS2 nanosheets did not induce significant changes in the cell morphologies, but they seemed to impair the cell division of HDFs. CS-MoS2 nanosheets (100 μg/mL) activated EGFR and induced reactive oxygen species, Smad, and IL-1, which in turn led to cell inflammation and apoptosis. Furthermore, HDFs showed cellular stress responses when they were exposed to low concentrations of CS-MoS2 nanosheets (25...

A mono approach to cancer therapy usually fails to achieve satisfactory results due to its limited killing effect. Nanostructured lipid carriers (NLCs) with high biocompatibility as well as tumor targetability were successfully designed and formulated in our study to co-deliver paclitaxel (PTX) and indocyanine green (ICG) for combined chemo and photodynamic therapy. ICG not only acted as an imaging reagent but also as a laser responsive agent to aid accelerated drug release under laser irritation. It has been demonstrated that our drug delivery system (DDS) not only significantly enhanced the stability of drugs, produced sufficient local ROS and triggered accelerated drug release upon laser irradiation, but also increased intracellular uptake of drugs and induced increased cytotoxicity in cancer cells via synergistic effects. Moreover, NLCs demonstrated excellent tumor targetability in tumor-bearing mice. Therefore, tumor targeted co-delivery of PTX and ICG mediated by NLCs could be a promising approach for further development as an effective strategy for cancer therapy.

Retraction of ‘A multifunctional self-dissociative polyethyleneimine derivative coating polymer for enhancing the gene transfection efficiency of DNA/polyethyleneimine polyplexes in vitro and in vivo’ by Cheng Wang, et al., Polym. Chem., 2015, 6, 780–796.

A new pH-responsive charge-conversion and rapidly self-dissociative multifunctional polymer lauric acid-polyethyleneimine-cyclohexanedicarboxylic anhydride-folic acid (LA-PEI-HHPA-FA, LPHF) is developed. LPHF as an amide with neighboring carboxylic acid groups becomes negatively charged at physiological pH and was used as a coating polymer to shield positively charged DNA/polyethyleneimine 25 k (DP) binary polyplexes, resulting in the formation of DPLPHF ternary polyplexes. The characterization using various methods proved that DPLPHF ternary polyplexes are stable at physiological pH, while in acidic endosomes, the coating polymer LPHF could quickly self-dissociate from the DP binary polyplexes. As compared with DP binary polyplexes, DPLPHF ternary polyplexes containing the tumor targeting ligand folic acid (FA), the absorption enhancer lauric acid (LA) and the charge-conversion entity cis-1,2-cyclohexanedicarboxylic anhydride (HHPA) exhibited more effective cellular uptake and higher transfection efficiency with lower non-therapeutic cytotoxicity in vitro. Moreover, in vivo studies revealed the significantly stronger tumor targeting and tumor inhibiting efficacy of DPLPHF ternary polyplexes. All these findings demonstrated the potential of LPHF as a promising coating polymer for enhanced gene transfection efficiency of DP binary polyplexes in vitro and in vivo.

Single-walled carbon nanotubes (SWNTs) with unique physicochemical properties have exhibited promising biomedical applications as drug and gene carriers. In this study, polyethylenimine (PEI)-modified SWNT conjugates linked with candesartan (CD) were developed to deliver vascular endothelial growth factor (VEGF)-targeted siRNA (siVEGF) for the synergistic and targeted treatment of tumor angiogenesis. The characterization results revealed that SWNT–PEI–CD conjugates were successfully synthesized and exhibited desirable dispersibility and superior stability. Confocal laser scanning microscopy (CLSM) and flow cytometry (FCM) results showed that SWNT–PEI–CD/siVEGF complexes could achieve high cellular uptake and specific intracellular distribution of siRNA in AT1R overexpressed PANC-1 cells. Strong down-regulation of VEGF was also verified by qualitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blot in complex-treated PANC-1 cells. The in vitro angiogenesis assay sho...

Multi-walled carbon nanotube (MWNT) with its versatility has exhibited tremendous superiority in drug delivery. Despite plenty of researches on MWNT based delivery systems, precision-guided assistances to maximize their profitable properties are still lacking in substantive progress. We developed here a dual-targeting and co-delivery system based on MWNT for antiangiogenesis therapy in lung cancer which aimed at renin-angiotensin system (RAS) dysregulation by synergistically conducting angiotensin II type 1 receptor (AT1R) and type 2 receptor (AT2R) pathway. In this work, iRGD peptide connected to polyethyleneimine (PEI) was linked to MWNT skeleton, accompanying with candesartan (CD) conjugated to MWNT mediated by cystamine (SS). The functionalized MWNT is assembled with plasmid AT2 (pAT2) to form iRGD-PEI-MWNT-SS-CD/pAT2 complexes. iRGD and CD act as pilots for complexes to dually target symbolic ανβ3-integrin and AT1R both overexpressed on tumor angiogenic endothelium and lung cancer cell. CD as chemotherapy showed synergistic downregulation of VEGF when combining of pAT2 and efficiently inhibited angiogenesis. iRGD-PEI-MWNT-SS-CD/pAT2 complexes greatly appreciated drug activities by changing drug distribution and exhibited remarkable tumor growth suppression in A549 xenograft nude mice. Our work presents that such dual-targeting strategy highly improves the delivery performance of MWNT and open a new avenue for RAS related lung cancer therapy.

A new cationic polymer eprosartan-graft-PEI (ESP) containing eprosartan (ES) and polyethylenimine 1.8K was successfully developed and employed as a safe gene vector to assemble a drug (ES) and gene co-delivery complex (ESP/pDNA). Chondroitin sulfate (CS) was then used as a coating polymer to shield the surface charge of ESP/pDNA complexes, as well as a tumor targeting entity to ensure specific delivery of CS/ESP/pDNA complexes. The CS/ESP/pDNA complexes with desirable particle size and zeta potential, exhibited amidase-responsive drug release and CS-mediated endocytosis in vitro. As compared with ESP/pDNA complexes, in vivo imaging results demonstrated decreased reticuloendothelial system uptake and remarkably increased tumor accumulation of CS/ESP/pDNA complexes. All these findings indicated the potential of CS/ESP/pDNA as a promising tumor-targeted drug and gene co-delivery system.

RNA interference holds tremendous potential as a therapeutic approach of malignant tumors. However, safe and efficient nanovectors are extremely lack for systemic delivery of small interfering RNA (siRNA). The study aimed to develop a biomimetic nanovector, reconstituted high density lipoprotein (rHDL), mediating targeted cholesterol-conjugated siRNA (Chol-siRNA) delivery for Pokemon gene silencing therapy. Chol-siRNA-loaded rHDL nanoparticles (rHDL/Chol-siRNA complexes) were prepared using thin-film dispersion method and their characteristics were investigated in detail. RHDL/Chol-siRNA complexes at the optimal volume ratio (lipid: Chol-siRNA) exhibited high Chol-siRNA-loading efficiency (~99%), desirable nanoparticle size and excellent stability in serum. In addition, by analyzing Chol-siRNA release profile, rHDL/Chol-siRNA complexes displayed sustained-release characteristic and storage stability. Observations from FACS and confocal microscopic analyses revealed that rHDL-mediated carboxyfluorescein tagged Chol-siRNA (FAM-Chol-siRNA) transfection resulted in highly efficient uptake and specific cytoplasmic delivery of FAM-Chol-siRNA into human hepatocellular carcinoma cell line HepG2 via HDL-receptor mediated mechanism. In vitro cytotoxicity, apoptosis and Western-blot analyses revealed significant cellular growth inhibition and decrease of Pokemon and Bcl-2 protein expression in HepG2 cells treated with Chol-siRNA-Pokemon-loaded rHDL nanoparticles (rHDL/Chol-siRNA-Pokemon complexes), respectively. In in vivo studies, the near-infrared (NIR) dye Cy5 labeled Chol-siRNA-loaded rHDL nanoparticles (rHDL/Cy5-Chol-siRNA complexes) obviously accumulated in tumor of nude mice after i.v. administration as compared with Cy5-Chol-siRNA-loaded lipoplexes (Lipos/Cy5-Chol-siRNA complexes). Morover, rHDL/Chol-siRNA-Pokemon complexes demonstrated great tumor growth inhibition and significant decrease of Pokemon and Bcl-2 protein expression in vivo. These results suggested that rHDL should be an ideal non-viral tumor-targeting vector for Chol-siRNA transfer, and rHDL-mediated Chol-siRNA-Pokemon delivery might be a promising new strategy for gene therapy in hepatocellular carcinoma.