Yang H.,National Engineering Research Center for Nanomedicine |
Wang Q.,Huazhong University of Science and Technology |
Chen W.,National Engineering Research Center for Nanomedicine |
Zhao Y.,National Engineering Research Center for Nanomedicine |
And 4 more authors.
Molecular Pharmaceutics | Year: 2015
Long circulation in the blood, efficient cellular internalization, and intracellular drug release in the tumor cells are major challenges in the development of ideal anticancer drug delivery systems. In this paper, hydrophilicity/hydrophobicity reversable and redox-sensitive poly(oligo(ethylene glycol) methacrylates-ss-acrylic acid) (P(OEGMAs-ss-AA)) nanogels were constructed as drug carriers for cancer therapy. The nanogels underwent a pH-dependent hydrophilic/hydrophobic change. The nanogels were hydrophilic under physiological conditions (pH 7.4, 37 °C), resulting in fewer opsonization of proteins and less phagocytosis by macrophage RAW264.7 cells, while they were hydrophobic in the tumor tissues (pH 6.5, 37 °C), resulting in strong internalization by Bel7402 cells. The doxorubicin (DOX) release from DOX-loaded nanogels was increased in intracellular reductive and lysosome acidic environments. DOX-loaded nanogels exhibited higher cellular proliferation inhibition to GSH-OEt-pretreated Bel7402 cells at pH 6.5 than to unpretreated cells at pH 7.4. Further studies showed that the loaded DOX and nanogels were internalized into the cells together via both lipid raft/caveolae- and clathrin-mediated endocytic pathways. After internalization, the DOX-loaded nanogels were transported via the specific route in endo/lysosomal system. The loaded DOX was released from the nanogels with the introduction of intracellular GSH and entered the nucleus. This study indicated that the hydrophilicity/hydrophobicity reversable and redox-sensitive nanogels might be used as potential carriers for anticancer drugs, which provided a foundation for designing an effective drug delivery system for cancer therapy. © 2015 American Chemical Society.
Zhou Q.,National Engineering Research Center for Nanomedicine |
Mu K.,Huazhong University of Science and Technology |
Jiang L.,National Engineering Research Center for Nanomedicine |
Xie H.,China Patent Information Center |
And 8 more authors.
International Journal of Nanomedicine | Year: 2015
Surgical resection is the primary mode for glioma treatment, while gross total resection is difficult to achieve, due to the invasiveness of the gliomas. Meanwhile, the tumor-resection region is closely related to survival rate and life quality. Therefore, we developed optical/magnetic resonance imaging (MRI) bifunctional targeted micelles for glioma so as to delineate the glioma location before and during operation. The micelles were constructed through encapsulation of hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) with polyethylene glycol-block-polycaprolactone (PEG-b-PCL) by using a solvent-evaporation method, and modified with a near-infrared fluorescent probe, Cy5.5, in addition to the glioma-targeting ligand lactoferrin (Lf). Being encapsulated by PEG-b-PCL, the hydrophobic SPIONs dispersed well in phosphate-buffered saline over 4 weeks, and the relaxivity (r2) of micelles was 215.4 mM-1⋅s-1, with sustained satisfactory fluorescent imaging ability, which might have been due to the interval formed by PEG-b-PCL for avoiding the fluorescence quenching caused by SPIONs. The in vivo results indicated that the nanoparticles with Lf accumulated efficiently in glioma cells and prolonged the duration of hypointensity at the tumor site over 48 hours in the MR image compared to the nontarget group. Corresponding with the MRI results, the margin of the glioma was clearly demarcated in the fluorescence image, wherein the average fluorescence intensity of the tumor was about fourfold higher than that of normal brain tissue. Furthermore, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay results showed that the micelles were biocompatible at Fe concentrations of 0-100 μg/mL. In general, these optical/MRI bifunctional micelles can specifically target the glioma and provide guidance for surgical resection of the glioma before and during operation. © 2015 Zhou et al.
Leng F.,National Engineering Research Center for Nanomedicine |
Leng F.,Huazhong University of Science and Technology |
Wan J.,National Engineering Research Center for Nanomedicine |
Wan J.,Huazhong University of Science and Technology |
And 6 more authors.
Regional Anesthesia and Pain Medicine | Year: 2012
Background and Objectives: Solid lipid nanoparticles (SLNs), as a drug carrier, are a very attractive strategy for sustained and controlled drug release. In this study, we investigated the feasibility of SLNs to prolong the action of lidocaine for potential application in epidural anesthesia and analgesia. Methods: Lidocaine-loaded SLNs were prepared with different lipids, including monostearin (MS), glyceryl palmitostearate (GP), and stearic acid (SA). The morphology and crystallinity were characterized with transmission electron microscopy and powder x-ray diffraction. In vitro release studies were carried in phosphate buffer solution of pH 7.4 using cellulose dialysis membrane. The in vivo efficacy of epidural anesthesia was evaluated in rats. Results: Lidocaine was successfully incorporated in SLNs prepared with MS, GP, and SA, respectively. The particle sizes of lidocaine-loaded SLNs were 143 to 388 nm with polydispersity index of 0.29 to 0.45. Powder x-ray diffraction analysis showed that lidocaine was mainly dispersed in SLNs in an amorphous state. The in vitro release within 48 hrs showed that lidocaine released from SLNs was 80% with MS SLNs, 69% with GP SLNs, and 89% with SA SLNs. The epidural efficacy was compared with that of aqueous lidocaine HCl. Single injection of lidocaine SLN suspension produced epidural block for more than 8 hrs with MS SLNs, 12 hrs with GP SLNs, and 4 hrs with SA SLNs. ]The same dose of lidocaine in aqueous solution lasted for less than 2 hrs. Conclusions: Solid lipid nanoparticles can be exploited as a promising drug carrier for extending the action of lidocaine. Copyright © 2012 by American Society of Regional Anesthesia and Pain Medicine.
Xiong W.,Huazhong University of Science and Technology |
Xiong W.,National Engineering Research Center for Nanomedicine |
Wang W.,National Engineering Research Center for Nanomedicine |
Wang Y.,National Engineering Research Center for Nanomedicine |
And 7 more authors.
Colloids and Surfaces B: Biointerfaces | Year: 2011
In this paper, a dual temperature/pH-sensitive poly(N-isopropylacrylamide-co-acrylic acid) nanogel (PNA) was prepared and utilized as a drug carrier. The anti-cancer drug doxorubicin (DOX) was covalent bound to PNA via an acid-labile hydrazone linkage. DOX-PNA conjugates had a pH-dependent LCST, which was 41 °C and 43 °C at pH 5.3 and 6.8 respectively, but higher than 50 °C at pH 7.4. The nanogels which were hydrophilic below LCST and changed to hydrophobic state above LCST possessed dual pH/temperature dependent cellular uptake and cytotoxicity. With increasing temperature, the cellular uptake of DOX-PNA was almost no difference at pH 7.4, but enhanced about 43% at pH 6.8. So the cytotoxicity of DOX-PNA also increased in higher temperature and lower pH value. It was able to distinguish tumor extracellular pH from physiological pH under hyperthermia of 43 °C, suggesting a great potential for anti-cancer therapy. © 2011 Elsevier B.V.
Chen H.,Huazhong University of Science and Technology |
Chen H.,National Engineering Research Center for Nanomedicine |
Zhu H.,Huazhong University of Science and Technology |
Zhu H.,National Engineering Research Center for Nanomedicine |
And 12 more authors.
ACS Nano | Year: 2011
Assembly of nanoparticles as interfacial stabilizers at oil-in-water (O/W) interfaces into microscopic suprastructures for stabilizing Pickering emulsions is an intriguing focus in the fields of chemical industry and material sciences. However, it is still a major challenge to assemble nanoscale suprastructures using nanoparticles as building blocks at O/W interfaces for fabricating nanoscale emulsion droplets with applicable potential in nanomedicine. Here, we show that it is possible to fabricate the nanodroplets by assembling highly deformable nanogels into the nanoscale suprastructures at spatially confined O/W interfaces. The compressed assembly of the nanogels induced the formation of the nanoscale suprastructures upon energy input at the nanoscale O/W interface. The hydrogen bonding interaction between the nanogels at the O/W interface are possibly responsible for the stabilization of the nanoscale suprastructures. The nanoscale suprastructures are further employed to stabilize the paclitaxel-loaded nanodroplets, which are found to provide sustained release of the drug, enhanced in vitro cytotoxicity, and prolonged in vivo blood circulation. Furthermore, the tissue distribution and antitumor efficacy studies show that the nanodroplets could induce a higher drug accumulation at the tumor site and enhance tumor growth inhibition when compared with the commercial product. This approach provides a novel universal strategy to fabricate nanoscale suprastructures for stabilizing nanodroplets with built-in payloads using deformable nanoparticles and displays a promising potential in nanomedicine. © 2011 American Chemical Society.