Browsing by Author "Shen, Mingwu"
Now showing 1 - 10 of 11
Results Per Page
Sort Options
- Antitumor efficacy of doxorubicin encapsulated within PEGylated poly(amidoamine) dendrimersPublication . Liao, Huihui; Liu, Hui; Li, Yulin; Zhang, Mengen; Tomás, Helena; Shen, Mingwu; Shi, XiangyangWe report here a general approach to using poly(amidoamine) (PAMAM) dendrimers modified with polyethylene glycol (PEG) as a platform to encapsulate an anticancer drug doxorubicin (DOX) for in vitro cancer therapy applications. In this approach, PEGylated PAMAM dendrimers were synthesized by conjugating monomethoxypolyethylene glycol with carboxylic acid end group (mPEG-COOH) onto the surface of generation 5 amine-terminated PAMAM dendrimer (G5.NH2), followed by acetylation of the remaining dendrimer terminal amines. By varying the molar ratios of mPEG-COOH/G5.NH2, G5.NHAc-mPEGn (n55, 10, 20, and 40, respectively) with different PEGylation degrees were obtained. We show that the PEGylated dendrimers are able to encapsulate DOX with approximately similar loading capacity regardless of the PEGylation degree. The formed dendrimer/DOX complexes are water soluble and stable. In vitro release studies show that DOX complexed with the PEGylated dendrimers can be released in a sustained manner. Further cell viability assay in conjunction with cell morphology observation demonstrates that the G5.NHAc-mPEGn/DOX complexes display effective antitumor activity, and the DOX molecules encapsulated within complexes can be internalized into the cell nucleus, similar to the free DOX drug. Findings from this study suggest that PEGylated dendrimers may be used as a general drug carrier to encapsulate various hydrophobic drugs for different therapeutic applications.
- Attapulgite-doped electrospun poly(lactic-co-glycolic acid) nanofibers enable enhanced osteogenic differentiation of human mesenchymal stem cellsPublication . Wang, Zhe; Zhao, Yili; Luo, Yu; Wang, Shige; Shen, Mingwu; Tomás, Helena; Zhu, Meifang; Shi, XiangyangThe extracellular matrix mimicking property of electrospun polymer nanofibers affords their uses as an ideal scaffold material for differentiation of human mesenchymal stem cells (hMSCs), which is important for various tissue engineering applications. Here, we report the fabrication of electrospun poly(lactic-co-glycolic acid) (PLGA) nanofibers incorporated with attapulgite (ATT) nanorods, a clay material for osteogenic differentiation of hMSCs. We show that the incorporation of ATT nanorods does not significantly change the uniform morphology and the hemocompatibility of the PLGA nanofibers; instead the surface hydrophilicity and cytocompatibility of the hybrid nanofibers are slightly improved after doping with ATT. Alkaline phosphatase activity, osteocalcin secretion, calcium content, and von Kossa staining assays reveal that hMSCs are able to be differentiated to form osteoblast-like cells onto both PLGA and PLGA–ATT composite nanofibers in osteogenic medium. Most strikingly, the doped ATT within the PLGA nanofibers is able to induce the osteoblastic differentiation of hMSCs in growth medium without the inducing factor of dexamethasone. The fabricated organic/inorganic hybrid ATT-doped PLGA nanofibers may find many applications in the field of tissue engineering and regenerative medicine.
- Carbon nanotube-incorporated multilayered cellulose acetate nanofibers for tissue engineering applicationsPublication . Luo, Yu; Wang, Shige; Shen, Mingwu; Qi, Ruiling; Fang, Yi; Guo, Rui; Cai, Hongdong; Cao, Xueyan; Tomás, Helena; Zhu, Meifang; Shi, XiangyangWe report the fabrication of a novel carbon nanotube-containing nanofibrous polysaccharide scaffolding material via the combination of electrospinning and layer-by-layer (LbL) self-assembly techniques for tissue engineering applications. In this approach, electrospun cellulose acetate (CA) nanofibers were assembled with positively charged chitosan (CS) and negatively charged multiwalled carbon nanotubes (MWCNTs) or sodium alginate (ALG) via a LbL technique. We show that the 3-dimensional fibrous structures of the CA nanofibers do not appreciably change after the multilayered assembly process except that the surface of the fibers became much rougher than that before assembly. The incorporation of MWCNTs in the multilayered CA fibrous scaffolds tends to endow the fibers with improved mechanical property and promote fibroblast attachment, spreading, and proliferation when compared with CS/ALG multilayer-assembled fibrous scaffolds. The approach to engineering the nanofiber surfaces via LbL assembly likely provides many opportunities for new scaffolding materials design in various tissue engineering applications.
- Electrospun laponite-doped poly(lactic-co-glycolic acid) nanofibers for osteogenic differentiation of human mesenchymal stem cellsPublication . Wang, Shige; Castro, Rita; An, Xiao; Song, Chenlei; Luo, Yu; Shen, Mingwu; Tomás, Helena; Zhu, Meifang; Shi, XiangyangWe report the fabrication of uniform electrospun poly(lactic-co-glycolic acid) (PLGA) nanofibers incorporated with laponite (LAP) nanodisks, a synthetic clay material for osteogenic differentiation of human mesenchymal stem cells (hMSCs). In this study, a solution mixture of LAP suspension and PLGA was electrospun to form composite PLGA–LAP nanofibers with different LAP doping levels. The PLGA–LAP composite nanofibers formed were systematically characterized via different techniques. We show that the incorporation of LAP nanodisks does not significantly change the uniform PLGA fiber morphology, instead significantly improves the mechanical durability of the nanofibers. Compared to LAP-free PLGA nanofibers, the surface hydrophilicity and protein adsorption capacity of the composite nanofibers slightly increase after doping with LAP, while the hemocompatibility of the fibers does not appreciably change. The cytocompatibility of the PLGA–LAP composite nanofibers was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay of L929 mouse fibroblasts and porcine iliac artery endothelial cells cultured onto the surface of the nanofibers. The results reveal that the incorporated LAP is beneficial to promote the cell adhesion and proliferation to some extent likely due to the improved surface hydrophilicity and protein adsorption capability of the fibers. Finally, the PLGA–LAP composite nanofibers were used as scaffolds for osteogenic differentiation of hMSCs. We show that both PLGA and PLGA–LAP composite nanofibers are able to support the osteoblast differentiation of hMSCs in osteogenic medium. Most strikingly, the doped LAP within the PLGA nanofibers is able to induce the osteoblast differentiation of hMSCs in growth medium without any inducing factors. The fabricated smooth and uniform organic–inorganic hybrid LAP-doped PLGA nanofibers may find many applications in the field of tissue engineering.
- Gene delivery using dendrimer-entrapped gold nanoparticles as nonviral vectorsPublication . Shan, Yuebin; Luo, Ting; Peng, Chen; Sheng, Ruilong; Cao, Amin; Cao, Xueyan; Shen, Mingwu; Guo, Rui; Tomás, Helena; Shi, XiangyangDevelopment of highly efficient nonviral gene delivery vectors still remains a great challenge. In this study, we report a new gene delivery vector based on dendrimer-entrapped gold nanoparticles (Au DENPs) with significantly higher gene transfection efficiency than that of dendrimers without AuNPs entrapped. Amine-terminated generation 5 poly(amidoamine) (PAMAM) dendrimers (G5.NH(2)) were utilized as templates to synthesize AuNPs with different Au atom/dendrimer molar ratios (25:1, 50:1, 75:1, and 100:1, respectively). The formed Au DENPs were used to complex two different pDNAs encoding luciferase (Luc) and enhanced green fluorescent protein (EGFP), respectively for gene transfection studies. The Au DENPs/pDNA polyplexes with different N/P ratios and compositions of Au DENPs were characterized by gel retardation assay, light scattering, zeta potential measurements, and atomic force microscopic imaging. We show that the Au DENPs can effectively compact the pDNA, allowing for highly efficient gene transfection into the selected cell lines as demonstrated by both Luc assay and fluorescence microscopic imaging of the EGFP expression. The transfection efficiency of Au DENPs with Au atom/dendrimer molar ratio of 25:1 was at least 100 times higher than that of G5.NH(2) dendrimers without AuNPs entrapped at the N/P ratio of 2.5:1. The higher gene transfection efficiency of Au DENPs is primarily due to the fact that the entrapment of AuNPs helps preserve the 3-dimensional spherical morphology of dendrimers, allowing for more efficient interaction between dendrimers and DNA. With the less cytotoxicity than that of G5.NH(2) dendrimers demonstrated by thiazoyl blue tetrazolium bromide assay and higher gene transfection efficiency, it is expected that Au DENPs may be used as a new gene delivery vector for highly efficient transfection of different genes for various biomedical applications.
- Modulation of Macrophages Using Nanoformulations with Curcumin to Treat Inflammatory Diseases: A Concise ReviewPublication . Sun, Huxiao; Zhan, Mengsi; Mignani, Serge; Shcharbin, Dzmitry; Majoral, Jean-Pierre; Rodrigues, João; Shi, Xiangyang; Shen, MingwuCurcumin (Cur), a traditional Chinese medicine extracted from natural plant rhizomes, has become a candidate drug for the treatment of diseases due to its anti-inflammatory, anticancer, antioxidant, and antibacterial activities. However, the poor water solubility and low bioavailability of Cur limit its therapeutic effects for clinical applications. A variety of nanocarriers have been successfully developed to improve the water solubility, in vivo distribution, and pharmacokinetics of Cur, as well as to enhance the ability of Cur to polarize macrophages and relieve macrophage oxidative stress or anti-apoptosis, thus accelerating the therapeutic effects of Cur on inflammatory diseases. Herein, we review the design and development of diverse Cur nanoformulations in recent years and introduce the biomedical applications and potential therapeutic mechanisms of Cur nanoformulations in common inflammatory diseases, such as arthritis, neurodegenerative diseases, respiratory diseases, and ulcerative colitis, by regulating macrophage behaviors. Finally, the perspectives of the design and preparation of future nanocarriers aimed at efficiently exerting the biological activity of Cur are briefly discussed.
- Multifunctional dendrimer-entrapped gold nanoparticles conjugated with Doxorubicin for pH-responsive drug delivery and targeted computed tomography imagingPublication . Zhu, Jingyi; Wang, Guoying; Alves, Carla S.; Tomás, Helena; Xiong, Zhijuan; Shen, Mingwu; Rodrigues, João; Shi, XiangyangNovel theranostic nanocarriers exhibit a desirable potential to treat diseases based on their ability to achieve targeted therapy while allowing for real-time imaging of the disease site. Development of such theranostic platforms is still quite challenging. Herein, we present the construction of multifunctional dendrimer-based theranostic nanosystem to achieve cancer cell chemotherapy and computed tomography (CT) imaging with targeting specificity. Doxorubicin (DOX), a model anticancer drug, was first covalently linked onto the partially acetylated poly(amidoamine) dendrimers of generation 5 (G5) prefunctionalized with folic acid (FA) through acid-sensitive cis-aconityl linkage to form G5·NHAc-FA-DOX conjugates, which were then entrapped with gold (Au) nanoparticles (NPs) to create dendrimer-entrapped Au NPs (Au DENPs). We demonstrate that the prepared DOX-Au DENPs possess an Au core size of 2.8 nm, have 9.0 DOX moieties conjugated onto each dendrimer, and are colloid stable under different conditions. The formed DOX-Au DENPs exhibit a pH-responsive release profile of DOX because of the cis-aconityl linkage, having a faster DOX release rate under a slightly acidic pH condition than under a physiological pH. Importantly, because of the coexistence of targeting ligand FA and Au core NPs as a CT imaging agent, the multifunctional DOX-loaded Au DENPs afford specific chemotherapy and CT imaging of FA receptor-overexpressing cancer cells. The constructed DOX-conjugated Au DENPs hold a promising potential to be utilized for simultaneous chemotherapy and CT imaging of various types of cancer cells.
- Phosphorus dendron nanomicelles as a platform for combination anti-inflammatory and antioxidative therapy of acute lung injuryPublication . Li, Jin; Chen, Liang; Li, Changsheng; Fan, Yu; Zhan, Mengsi; Sun, Huxiao; Mignani, Serge; Majoral, Jean-Pierre; Shen, Mingwu; Shi, XiangyangRationale: Development of novel nanomedicines to inhibit pro-inflammatory cytokine expression and reactive oxygen species (ROS) generation for anti-inflammatory therapy of acute lung injury (ALI) remains challenging. Here, we present a new nanomedicine platform based on tyramine-bearing two dimethylphosphonate sodium salt (TBP)-modified amphiphilic phosphorus dendron (C11G3) nanomicelles encapsulated with antioxidant drug curcumin (Cur). Methods: C11G3-TBP dendrons were synthesized via divergent synthesis and self-assembled to generate nanomicelles in a water environment to load hydrophobic drug Cur. The created C11G3-TBP@Cur nanomicelles were well characterized and systematically examined in their cytotoxicity, cellular uptake, intracellular ROS elimination, pro-inflammatory cytokine inhibition and alveolar macrophages M2 type repolarization in vitro, and evaluated to assay their anti-inflammatory and antioxidative therapy effects of ALI mice model through pro-inflammatory cytokine expression level in bronchoalveolar lavage fluid and lung tissue, histological analysis and micro-CT imaging detection of lung tissue injury in vivo. Results: The nanomicelles with rigid phosphorous dendron structure enable high-capacity and stable Cur loading. Very strikingly, the drug-free C11G3-TBP micelles exhibit excellent cytocompatibility and intrinsic anti-inflammatory activity through inhibition of nuclear transcription factor-kappa B, thus causing repolarization of alveolar macrophages from M1 type to anti-inflammatory M2 type. Taken together with the strong ROS scavenging property of the encapsulated Cur, the developed nanomicelles enable effective therapy of inflammatory alveolar macrophages in vitro and an ALI mouse model in vivo after atomization administration. Conclusion: The created phosphorus dendron nanomicelles can be developed as a general nanomedicine platform for combination anti-inflammatory and antioxidative therapy of inflammatory diseases.
- Polyethylenimine nanogels incorporated with ultrasmall iron oxide nanoparticles and doxorubicin for MR imaging-guided chemotherapy of tumorsPublication . Zou, Yu; Li, Du; Wang, Yue; Ouyang, Zhijun; Peng, Yucheng; Tomás, Helena; Xia, Jindong; Rodrigues, João; Shen, Mingwu; Shi, XiangyangDevelopment of versatile nanoplatforms for cancer theranostics remains a hot topic in the area of nanomedicine. We report here a general approach to create polyethylenimine (PEI)-based hybrid nanogels (NGs) incorporated with ultrasmall iron oxide (Fe3O4) nanoparticles (NPs) and doxorubicin for T1-weighted MR imaging guided chemotherapy of tumors. In this study, PEI NGs were first prepared using an inverse emulsion approach along with Michael addition reaction to cross-link the NGs, modified with citric acid stabilized ultrasmall Fe3O4 NPs through 1-ethyl-3-(3-(dimethylamino)- propyl) carbodiimide hydrochloride (EDC) coupling, and physically loaded with anticancer drug doxorubicin (DOX). The formed hybrid NGs possess good water dispersibility and colloidal stability, excellent DOX loading efficiency (51.4%), pH-dependent release profile of DOX with an accelerated release rate under acidic pH, and much higher r1 relaxivity (2.29 mM−1 s −1 ) than free ultrasmall Fe3O4 NPs (1.15 mM−1 s −1 ). In addition, in contrast to the drug-free NGs that possess good cytocompatibility, the DOX-loaded hybrid NGs display appreciable therapeutic activity and can be taken up by cancer cells in vitro. With these properties, the developed hybrid NGs enabled effective inhibition of tumor growth under the guidance of T1-weighted MR imaging. The developed hybrid NGs may be applied as a versatile nanoplatform for MR imaging-guided chemotherapy of tumors.
- Superstructured poly(amidoamine) dendrimer-based nanoconstructs as platforms for cancer nanomedicine: a concise reviewPublication . Song, Cong; Shen, Mingwu; Rodrigues, João; Mignani, Serge; Majoral, Jean-Pierre; Shi, XiangyangPoly(amidoamine) (PAMAM) dendrimers, as a family of synthetic macromolecules with highly branched interiors, abundant surface functional groups, and well-controlled architecture, have received immense scientific and technological interests for a range of biomedical applications, in particular cancer nanome dicine. However, due to the drawbacks of single-generation dendrimers with a quite small size (e.g., gen eration 5 (G5) PAMAM dendrimer has a size of 5.4 nm) such as limited drug loading capacity, restricted tumor passive targeting based on enhanced permeability and retention effect, and lack of versatility to render them with stimuli-responsiveness, superstructured dendrimeric nanoconstructs (SDNs) have been designed to break through these obstacles in their applications in cancer nanomedicine. Here, we review the recent advances related to the creation of SDNs such as dendrimer dumbbells, core–shell tecto den drimers, dendrimer nanoclusters (NCs), dendrimer nanogels and dendrimer-templated hybrid NCs, and how these SDNs have been designed as nanoplatforms for different biomedical applications related to cancer nanomedicine including MR imaging, drug/gene delivery, combination therapy and theranostics. This review concisely describes the latest key developments in the field and also discusses the possible challenges and perspectives for translation applications.