Hong Wu

Background: Dual loading drug delivery system with tumor targeting efficacy and sequential release function provides a promising platform for anticancer drug delivery. Herein, we established a novel AuCOOH@FACS nanogel system for co-delivery miR-218 mimics (as bio-drug) and Temozolomide(as chemo-drug). Methods: DLS and TEM were employed to determine the characteristics of particles and nanogels. The cell viability was calculated for study synergistic effect of both drugs coadministration and in nanogel forms. The amounts of Au uptake were measured by ICP-MS in cell and tumors to quantify the targeting drug delivery efficacy. Tumor weight and mice weight were investigated to study the targeting antitumor efficacy of nanogel system. Results: The results revealed that using AuCOOH@FACS nanogel as delivery vehicles, drugs could be targeting delivery to tumor site, the intracellular uptake is enhanced to a greater extent, and significant antitumor efficacy is fold increase compared with free drug administration group, without noticeable system cytotoxicity. Conclusions: This system offers an efficient approach to cancer therapy and holds significant potential to improve the treatment of cancer in the future.

Herein, we demonstrated the use of a newly generated anti FAT1 antibody (clone mAB198.3) for intracellular delivery of anionic gold NPs, to form active targeting Au nanoparticles with high payload characteristics. In vitro characterizations were determined by DLS, confocal microscopy, TEM, western blot, MALDI-TOF MS/MS analysis, MTT, ICP-MS and flow cytometry analysis. In vivo targeting efficacy was investigated by in vivo bio-imaging study and ICP-MS. The specificity of the FAT1 recognition in colon cancer was confirmed by pre-adsorbing mAb198.3, adsorption dramatically abolished the antibody reactivity on colon cancer, thus confirming the binding specificity. The DLS size distribution profile of the AuCOOH, AuCOOH(Cy5)_ mAb198.3, AuCOOH(Cy5)_isotype has showed that the modified gold nanoparticles are well dispersed in water, PBS buffer and cell culture medium with 10 % FBS. By TEM measurement, the size of Au nanoparticles with spherical morphology is about 10–20 nm. AuCOOH_198.3 NPs were stable in an acidic environment, as well as in PBS buffer, cell culture media and media with 10 % serum. MTT results revealed that Au nanoparticles have well biocompatibility. TEM results indicated that conjugation of mAb198.3 on Au nanoparticles can be an effective delivery vehicle for negatively charged gold nanoparticles and increased its intracellular transport. It was also demonstrated by confocal microscopy that AuCOOH(Cy5)_mAb198.3 could attach to the cell membrane in very short time, then gradually delivered into cells. After 4 h incubation, almost all AuCOOH(Cy5)_mAb198.3 have been uptaken into or surrounding the cytoplasm and nucleus. In vivo results showed that only about 20 % of AuCOOH accumulated in tumor site due to EPR effect, while nearly 90 % of AuCOOH_mAb198.3 was found in tumor, providing sufficient evidence for receptor-specific targeting by mAb198.3. According to in vitro and in vivo research results, the intracellular uptake of negatively charged AuCOOH_mAB198.3 particles is enhanced to a greater extent. Thus, AuCOOH_mAb198.3 holds significant potential to improve the treatment of cancer.

High-performance liquid chromatography with diode array detection (HPLC-DAD), time-of-flight mass spectrometry (HPLC-TOFMS) and quadrupole ion trap mass spectrometry (HPLC-QITMS) were used for separation and identification of multi-components in Psoralea corylifolia. Benefiting from combining the accurate mass measurement of HPLC-TOFMS to generate elemental compositions, the complementary multilevel structural information provided by HPLC-QITMS and the characteristic UV spectra obtained from HPLC-DAD, 24 components in P. corylifolia were identified. The five groups of isomers were differentiated based on the fragmentation behaviors in QITMS and UV spectra. It can be concluded that an effective method based on the combination of HPLC-DAD, HPLC-TOFMS and HPLC-QITMS for identification of chemical components in P. corylifolia was established. The results provide essential data for further pharmacological and clinical studies of P. corylifolia and facilitate the rapid quality control of the crude drug.

A facile and well‐controlled pathway was introduced to obtain optimal pH‐sensitive luteinizing hormone‐releasing hormone—functionalized poly(ethylene glycol)‐block‐poly(l‐histidine) (LHRH‐PEG‐PHIS) micelles in this paper. The influence of block‐selective solvent, the weight ratio of the selective solvent to common solvent and initial polymer concentration on the self‐assembly of LHRH‐PEG‐PHIS micelles were studied. These factors exerted remarkable influence on the morphology of the resulting micelles. The micelles showed a spherical geometry and an uniform appearance under the following optimal experimental conditions: LHRH‐PEG/PHIS ratio of 1.0 by molar, DMF as the selective solvent and 3.0 mg/mL as initial concentration, 100 W of ultrasonic power. These micelles had a small diameter (about 90 nm), low CMC (10 μg/mL), and pH‐sensitive switch in surface charge and micelles' size. As the pH of the micellar solution decreased from pH 7.4 to 5.5, the zeta potential of the LHRH‐PEG‐PHIS micelles increased from −0.02 mV to 20.7 mV and the diameter of the nanoparticles decreased from 137 nm to 76 nm. After 30 h of incubation at pH 5.0, 6.0, and 7.4 the released free Doxorubicin (DOX) was about 83.18%, 81.26%, and 30.35%, respectively. The LHRH‐PEG‐PHIS micelles could combine the characteristics of active targeting with pH‐triggered drug release promising as intracellular drug delivery carriers. POLYM. ENG. SCI., 55:277–286, 2015. © 2014 Society of Plastics Engineers

Ideal wound dressing materials should create a good healing environment, with immediate hemostatic effects and antimicrobial activity. In this study, chitosan/konjac glucomannan (CS/KGM) films embedded with gentamicin-loaded poly(dex-GMA/AAc) nanoparticles (giving GNP-CS/KGM films) were prepared as novel wound dressings. The results revealed that the modified CS/KGM films could be used as effective wound dressings and had significant hemostatic effects. With their microporous structure, the films could effectively absorb water from blood and trap blood cells. The gentamicinloaded poly(dex-GMA/AAc) nanoparticles (GNPs) also further promoted blood clotting, with their favorable water uptake capacity. Thus, the GNP-CS/KGM films had wound healing and synergistic effects that helped to stop bleeding from injuries, and also showed good antibiotic abilities by addition of gentamicin to the NPs. These GNPCS/KGM films can be considered as promising novel biodegradable and biocompatible wound dressings with hemostatic capabilities and antibiotic effects for treatment of external bleeding injuries.

The goal of this study was to develop doxorubicin conjugate nanoparticles with increased antitumor effects, reduced side effects and the ability to overcome multidrug resistance (MDR). In this regard, folate‐decorated maleilated pullulan–doxorubicin conjugate nanoparticles were developed as carriers for co‐delivery of pyrrolidinedithiocarbamate and doxorubicin (FA‐MP‐DOX/PDTC + DOX NPs). The resultant nanoparticles showed spherical geometry, with an average diameter of 152 nm. The two drugs were released from the nanoparticles in a slow, pH‐dependent sustained release. To test the efficacy of these nanoparticles, in vitro tests including cell viability and folate receptor‐mediated endocytosis were conducted against both A2780 cells and A2780/DOX^R cells. Compared to free DOX, the FA‐MP‐DOX/PDTC + DOX NPs showed effective but less potent cytotoxicity against A2780 cells. For A2780/DOX^R cells, they showed enhanced cellular uptake, increased targeting capacity and cytotoxicity. These results suggest that co‐delivery of PDTC and DOX may further overcome MDR by transporting an increased amount of DOX within cells in addition to the folate receptor‐mediated endocytosis process. © 2012 Society of Chemical Industry

BACKGROUND: Much interest has recently been shown in fundamental studies and technological developments of polymeric nanoparticles. Novel dual temperature‐ and pH‐sensitive stabilized nanoparticles composed of maleilated dextran (Dex‐MA) and N‐isopropylacrylamide (NIPAAm) were prepared and investigated to be used for the controlled release of 10‐hydroxycamptothecin.RESULTS: The resultant nanoparticles showed spherical geometry, with diameters ranging from 60 to 300 nm, the variation achieved by adjusting the composition ratio or the amounts of surfactant. The size of the nanoparticles increased and the zeta potential reversed with an increase of pH. Also, the lower critical solution temperature (LCST) decreased at pH = 3.0, but increased at pH = 6.0, which suggests that the LCST is dependent on pH. Drug release results obtained showed encapsulation and loading efficiencies were 62.9% and 0.82%, respectively. Cytotoxicity assay of this copolymer indicated no significant toxicity.CONCLUSION: Novel dual temperature‐ and pH‐sensitive Dex‐MA‐graft‐PNIPAAm nanoparticles may provide some advantages for anti‐cancer drug delivery due to a tunable LCST from 35 to 45 °C and controllable dimensions. These nanoscale materials could be excellent candidates for biotechnology and biomedical applications. Copyright © 2009 Society of Chemical Industry