Search results

Jun Li,1,* Wenqing Xu,2,* Xiaoli Yuan,3,* Huaiwen Chen,3 Hao Song,1,4 Bingquan Wang,5 Jun Han5 1College of Pharmacy, Liaocheng University, Liaocheng, Shandong, 2Railway Police College, Zhengzhou, 3Department of Cadre Health Care, Nanjing General Hospital of Nanjing Military Command, Nanjing, Jiangsu, 4Centre for Stem Cell & Regenerative Medicine, Liaocheng People's Hospital, 5Institute of Biopharmaceutical Research, Liaocheng University, Liaocheng, Shandong, China *These authors contributed equally to this work Purpose: Breast cancer stem cells (CSCs) are responsible for the initiation, recurrence, and metastasis of breast cancer. Sufficient evidence has established that breast cancer cells can spontaneously turn into breast CSCs. Thus, it is essential to simultaneously target breast CSCs and cancer cells to maximize the efficacy of breast cancer therapy. HER2 has been found to be overexpressed in both breast CSCs and cancer cells. We developed salinomycin-loaded polymer–lipid hybrid anti-HER2 nanoparticles (Sali-NP-HER2) to target both HER2-positive breast CSCs and cancer cells.Methods: The antitumor activity of Sali-NP-HER2 constructed by conjugating anti-HER2 antibodies to polymer–lipid salinomycin nanoparticles was evaluated in vitro and in vivo.Results: Sali-NP-HER2 efficiently bound to HER2-positive breast CSCs and cancer cells, resulting in enhanced cytotoxic effects compared with non-targeted nanoparticles or salinomycin. In mice bearing breast cancer xenografts, administration of Sali-NP-HER2 exhibited superior efficacy in inhibiting tumor growth. Sali-NP-HER2 reduced the breast tumorsphere formation rate and the proportion of breast CSCs more effectively than non-targeted nanoparticles or salinomycin alone.Conclusion: Sali-NP-HER2 represents a promising approach in treating HER2-positive breast cancer by targeting both breast CSCs and cancer cells. Keywords: nanoparticles, breast cancer, cancer stem cells, salinomycin, HER2

Xiaonan Guo,1,* Xiaoshuang Zhu,1,* Dakan Liu,1 Yubin Gong,1 Jing Sun,2 Changxian Dong1 1Department of Hemangioma and Vascular Malformation, Henan Provincial People's Hospital, Zhengzhou, People's Republic of China; 2Department of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China *These authors contributed equally to this work Purpose: To reduce the adverse effects and high frequency of administration of propranolol to treat infantile hemangioma, we first utilized propranolol-loaded liposomes-in-microsphere (PLIM) as a novel topical release system to realize sustained release of propranolol.Methods: PLIM was developed from encapsulating propranolol-loaded liposomes (PLs) in microspheres made of poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) copolymers (PLGA-PEG-PLGA). The release profile of propranolol from PLIM was evaluated, and its biological activity was investigated in vitro using proliferation assays on hemangioma stem cells (HemSCs). Tumor inhibition was studied in nude mice bearing human subcutaneous infantile hemangioma.Results: The microspheres were of desired particle size (~77.8 µm) and drug encapsulation efficiency (~23.9%) and achieved sustained drug release for 40 days. PLIM exerted efficient inhibition of the proliferation of HemSCs and significantly reduced the expression of two angiogenesis factors (vascular endothelial growth factor-A [VEGF-A] and basic fibroblast growth factor [bFGF]) in HemSCs. Notably, the therapeutic effect of PLIM in hemangioma was superior to that of propranolol and PL in vivo, as reflected by significantly reduced hemangioma volume, weight, and microvessel density. The mean hemangioma weight of the PLIM-treated group was significantly lower than that of other groups (saline =0.28 g, propranolol =0.21 g, PL =0.13 g, PLIM =0.03 g; PLIM vs saline: P<0.001, PLIM vs propranolol: P<0.001, PLIM vs PL: P<0.001). The mean microvessel density of the PLIM-treated group was significantly lower than that of other groups (saline =40 vessels/mm2, propranolol =31 vessels/mm2, PL =25 vessels/mm2, PLIM =11 vessels/mm2; PLIM vs saline: P<0.001, PLIM vs propranolol: P<0.01, PLIM vs PL: P<0.05).Conclusion: Our findings show that PLIM is a very promising approach to locally and efficiently deliver propranolol to the hemangioma site leading to a significant inhibition of infantile hemangioma. Keywords: propranolol, liposomes, microsphere, controlled release, hemangioma

Xiangwei Liu,1,* Naiwen Tan,1,* Yuchao Zhou,1 Hongbo Wei,1,* Shuai Ren,1 Fan Yu,2 Hui Chen,3 Chengming Jia,4 Guodong Yang,5 Yingliang Song1 1State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Implant Dentistry, 2Department of Prosthodontics, School of Stomatology, 3Department of Plastic Surgery, Tangdu Hospital, 4Department of Traditional Chinese Medicine, Xijing Hospital, 5Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China *These authors contributed equally to this work Abstract: Impaired osseointegration of the implant remains the big hurdle for dental implant therapy in diabetic patients. In this study, the authors first identified that miR204 was strikingly highly expressed in the bone mesenchymal stem cells (BMSCs) of diabetic rats. Forced expression of miR204 repressed the osteogenic potential of BMSCs, while inhibition of miR204 significantly increased the osteogenic capacity. Moreover, the miR204 inhibitor was conjugated with gold nanoparticles (AuNP-antagomiR204) and dispersed them in the poly(lactic-co-glycolic acid) (PLGA) solution. The AuNP-antagomiR204 containing PLGA solution was applied for coating the surface of titanium implant. Electron microscope revealed that an ultrathin sheet was formed on the surface of the implant, and the AuNPs were evenly dispersed in the coated PLGA sheet. Cellular experiments revealed that these encapsulated AuNP-antagomiR204 were able to be released from the PLGA sheet and uptaken by adherent BMSCs. In vivo animal study further confirmed that the AuNP-antagomiR204 released from PLGA sheet promoted osseointegration, as revealed by microcomputerized tomography (microCT) reconstruction and histological assay. Taken together, this study established that miR204 misexpression accounted for the deficient osseointegation in diabetes mellitus, while PLGA sheets aided the release of AuNP-antagomiR204, which would be a promising strategy for titanium implant surface functionalization toward better osseointegration. Keywords: osseointegration, miR204, PLGA sheets, gold nanoparticles, diabetes mellitus, titanium implant

Yurui Xu,1 Sajid Asghar,2 Shiya Gao,1 Zhipeng Chen,3 Lin Huang,1 Lining Yin,1 Qineng Ping,1 Yanyu Xiao11Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People's Republic of China; 2Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan; 3Department of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China Abstract: The aim of this study was to evaluate the potential of polyelectrolyte complex nanoparticles (PENPs) based on hyaluronic acid/chitosan hydrochloride (HA/HCS) for co-loading mitoxantrone (MTO) and verapamil (VRP) to overcome multidrug resistance in breast tumors. PENPs co-loaded with MTO and VRP (MTO-VRP-PENPs) were affected by the method of preparation, molecular weight of HA, mass ratios and initial concentrations of HA/HCS, pH, and drug quantities. Optimized MTO-VRP-PENPs were ~209 nm in size with a zeta potential of approximately −24 mV. Encapsulation efficiencies (%) of MTO and VRP were 98.33%±0.27% and 44.21%±8.62%, respectively. MTO and VRP were successfully encapsulated in PENPs in a molecular or amorphous state. MTO-VRP-PENPs showed significant cytotoxicity in MCF-7/ADR cells in contrast to MTO-loaded PENPs (MTO-PENPs). The reversal index of MTO-VRP-PENPs was 13.25 and 10.33 times greater than that of the free MTO and MTO-PENPs, respectively. In conclusion, MTO-VRP-PENPs may serve as a promising carrier to overcome tumor drug resistance.Keywords: hyaluronic acid, chitosan hydrochloride, mitoxantrone hydrochloride, verapamil hydrochloride, co-delivery, multidrug resistance

Zhongyang Liu,1,* Shu Zhu,1,* Liang Liu,2,* Jun Ge,3,4,* Liangliang Huang,1 Zhen Sun,1 Wen Zeng,5 Jinghui Huang,1 Zhuojing Luo1 1Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 2Department of Orthopedics, No 161 Hospital of PLA, Wuhan, Hubei, 3Department of Orthopedics, No 323 Hospital of PLA, Xi'an, Shaanxi, 4Department of Anatomy, Fourth Military Medical University, Xi'an, Shaanxi, 5Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China *These authors contributed equally to this work Abstract: Peripheral nerve repair is still challenging for surgeons. Autologous nerve transplantation is the acknowledged therapy; however, its application is limited by the scarcity of available donor nerves, donor area morbidity, and neuroma formation. Biomaterials for engineering artificial nerves, particularly materials combined with supportive cells, display remarkable promising prospects. Schwann cells (SCs) are the absorbing seeding cells in peripheral nerve engineering repair; however, the attenuated biologic activity restricts their application. In this study, a magnetic nanocomposite scaffold fabricated from magnetic nanoparticles and a biodegradable chitosan–glycerophosphate polymer was made. Its structure was evaluated and characterized. The combined effects of magnetic scaffold (MG) with an applied magnetic field (MF) on the viability of SCs and peripheral nerve injury repair were investigated. The magnetic nanocomposite scaffold showed tunable magnetization and degradation rate. The MGs synergized with the applied MF to enhance the viability of SCs after transplantation. Furthermore, nerve regeneration and functional recovery were promoted by the synergism of SCs-loaded MGs and MF. Based on the current findings, the combined application of MGs and SCs with applied MF is a promising therapy for the engineering of peripheral nerve regeneration. Keywords: peripheral nerve repair, magnetic nanoparticle, nanocomposite, magnetic field, Schwann cell, functional recovery

Cihui Tian,1 Sajid Asghar,2 Yifan Wu,1 Zhipeng Chen,3 Xin Jin,1 Lining Yin,1 Lin Huang,1 Qineng Ping,1 Yanyu Xiao1 1Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China; 2Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan; 3Department of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China Abstract: The expression of multiple receptors on intestinal epithelial cells enables an actively targeted carrier to significantly enhance the oral delivery of payloads. Conjugating the receptors' ligands on the surfaces of a particulate-delivery system allows site-specific targeting. Here, we used taurocholic acid (TCA) as a ligand for uptake of nanostructured lipid carriers (NLCs) mediated by a bile-acid transporter to improve oral bioavailability of curcumin (Cur). First, synthesis of TCA–polyethylene glycol 100–monostearate (S100-TCA) was carried out. Then, the physical and chemical properties of S100-TCA-modified Cur-loaded NLCs (Cur-TCA NLCs) with varying levels of S100-TCA modifications were investigated. Small particle size (90%), drug loading (about 3%), negative ζ-potential (–7 to –3 mV), and sustained release were obtained. In situ intestinal perfusion studies demonstrated improved absorption rate and permeability coefficient of Cur-TCA NLCs. Depending on the degree of modification, Cur-TCA NLCs displayed about a five- to 15-fold higher area under the curve in rats after oral administration than unmodified Cur NLCs, which established that the addition of S100-TCA to the NLCs boosted absorption of Cur. Further investigations of TCA NLCs might reveal a bright future for effective oral delivery of poorly bioavailable drugs. Keywords: curcumin, nanostructured lipid carriers, taurocholic acid, oral administration, pharmacokinetics, bioavailability

United Kingdom (UK) counter-terrorism strategy or known as CONTEST is government respond to threat of terrorism using four workstreams including Pursue, Prevent, Protect, and Prepare. Each workstreams representing target which UK's government is trying to achieve success indicators. Security means different thing to different states and is used to respond threat accordingly. CONTEST published in 2011 can be categorized in proactive approach as UK's effort to support mainstream Islam as part of government propaganda using programs under Prevent workstream. Proactive approach warned by scholar to have negative impact as it promotes group cohesion and self-sacrifice attitude from terrorism sympathizer. Furthermore, research findings about factors behind success and failure of counter-terrorism strategy one of them mention society relationship and trust towards government. However, according to data reviewing programs under CONTEST 2011, writer finds stigmatization towards Muslim community. Hence the failure of Prevent to achieve its success indicator become one of the motive endorses UK's foreign fighters involvement in Syria during 2011-2015.

Abdulrahman K Al-Asmari,1 Zabih Ullah,1 Ali Al Balowi,2 Mozaffarul Islam1 1Department of Research, Prince Sultan Military Medical City, Riyadh, 2Department of Pharmacy, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia Abstract: The use of liposomes in biological and medicinal sciences is a relatively new approach. The liposomal strategy greatly depends on the technological advancement in the formation of vesicles of various sizes and properties. In the current study, we encapsulated the venoms obtained from medically important scorpions such as Androctonus bicolor (AB), Androctonus crassicauda (AC), and Leiurus quinquestriatus (LQ). To begin with, our first and foremost aim was to prepare biocompatible and biodegradable nanovesicles. Additionally, we intended to enhance the anti-cancer potential of these encapsulated venoms. The liposomal venoms were prepared by rehydration and dehydration methods. Morphology, particle size, and size distribution of the liposomes were examined by scanning electron microscope (SEM), transmission electron microscope (TEM), and Zetasizer. We found that the prepared liposomes had a smooth surface and a spherical/ovoid shape and existed mainly as single unilamellar vesicles (SUVs). Furthermore, the liposomal formulation of all three venoms exhibited excellent stability and good encapsulation efficiency (EE). Additionally, the anti-cancer potential of the encapsulated venoms was also evaluated on a colorectal cancer cell line (HCT-8). The venom-loaded liposomes showed elevated anti-cancer properties such as low rate of cell survival, higher reactive oxygen species (ROS) generation, and enhancement in the number of apoptotic cells. In addition to this, cell cycle analysis revealed G0/G1 enrichment upon venom treatment. The effect of treatment was more pronounced when venom–liposome was used as compared to free venom on the HCT-8 cell line. Furthermore, we did not observe any interference of liposomal lipids used in these preparations on the progression of cancer cells. Considering these findings, we can conclude that the encapsulated scorpion venoms exhibit better efficacy and act more vigorously as an anti-cancer agent on the colorectal cancer cell line when compared with their free counterpart. Keywords: liposomes, scorpion venom, colon carcinoma cells, nanomedicine, anti-cancer

Hong-ye Yang,1 Li-na Niu,2 Jin-long Sun,2 Xue-qing Huang,3 Dan-dan Pei,4 Cui Huang,1 Franklin R Tay5 1The State Key Laboratory Breeding Base of Basic Science of Stomatology, Key Laboratory for Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei, People's Republic of China; 2State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Oral Diseases, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China; 3Department of Prosthodontics, Guanghua School and Hospital of Stomatology, Guangdong Key Laboratory of Stomatology, Yat-sen University, Guangzhou, Guangdong, People's Republic of China; 4Department of Prosthodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China; 5Department of Endodontics, College of Dental Medicine, Augusta University, Augusta, GA, USA Abstract: Scaffold supplements such as nanoparticles, components of the extracellular matrix, or growth factors have been incorporated in conventional scaffold materials to produce smart scaffolds for tissue engineering of damaged hard tissues. Due to increasing concerns on the clinical side effects of using large doses of recombinant bone-morphogenetic protein-2 in bone surgery, it is desirable to develop an alternative nanoscale scaffold supplement that is not only osteoinductive, but is also multifunctional in that it can perform other significant bone regenerative roles apart from stimulation of osteogenic differentiation. Because both amorphous calcium phosphate (ACP) and silica are osteoinductive, a biodegradable, nonfunctionalized, expanded-pore mesoporous silica nanoparticle carrier was developed for loading, storage, and sustained release of a novel, biosilicification-inspired, polyamine-stabilized liquid precursor phase of ACP for collagen biomineralization and for release of orthosilicic acid, both of which are conducive to bone growth. Positively charged poly(allylamine)-stabilized ACP (PAH-ACP) could be effectively loaded and released from nonfunctionalized expanded-pore mesoporous silica nanoparticles (pMSN). The PAH-ACP released from loaded pMSN still retained its ability to infiltrate and mineralize collagen fibrils. Complete degradation of pMSN occurred following unloading of their PAH-ACP cargo. Because PAH-ACP loaded pMSN possesses relatively low cytotoxicity to human bone marrow-derived mesenchymal stem cells, these nanoparticles may be blended with any osteoconductive scaffold with macro- and microporosities as a versatile scaffold supplement to enhance bone regeneration. Keywords: amorphous calcium phosphate, biomineralization, collagen, mesoporous silica, osteoinductive, poly(allylamine)

Jianfei Liang,1,* Shanshan Xu,1,* Mingming Shen,2,* Bingkun Cheng,3 Yongfeng Li,4 Xiangwei Liu,1 Dongze Qin,1 Anuj Bellare,5 Liang Kong1 1State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Disease & Shaanxi Key Laboratory of Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an, 2Department of Stomatology, Xinhua Hospital of Beijing, Beijing, 3Department of Oral and Maxillofacial Surgery, School of Stomatology, The Second Hospital of Hebei Medical University, Shijiazhuang, 4Department of Stomatology, Chinese PLA 532 Hospital, Huangshan, People's Republic of China; 5Department of Orthopedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA *These authors contributed equally to this work Abstract: An easier method for constructing the hierarchical micro-/nano-structures on the surface of dental implants in the clinic is needed. In this study, three different titanium surfaces with microscale grooves (width 0.5–1, 1–1.5, and 1.5–2 µm) and nanoscale nanoparticles (diameter 20–30, 30–50, and 50–100 nm, respectively) were obtained by treatment with different concentrations of hydrofluoric acid (HF) and at different etching times (1%, 3 min; 0.5%, 12 min; and 1.5%, 12 min, respectively; denoted as groups HF1, HF2, and HF3). The biological response to the three different titanium surfaces was evaluated by in vitro human bone marrow-derived mesenchymal stem cell (hBMMSC) experiments and in vivo animal experiments. The results showed that cell adhesion, proliferation, alkaline phosphatase activity, and mineralization of hBMMSCs were increased in the HF3 group. After the different surface implants were inserted into the distal femurs of 40 rats, the bone–implant contact in groups HF1, HF2, and HF3 was 33.17%±2.2%, 33.82%±3.42%, and 41.04%±3.08%, respectively. Moreover, the maximal pullout force in groups HF1, HF2, and HF3 was 57.92±2.88, 57.83±4.09, and 67.44±6.14 N, respectively. The results showed that group HF3 with large micron grooves (1.5–2.0 µm) and large nanoparticles (50–100 nm) showed the best bio-functionality for the hBMMSC response and osseointegration in animal experiments compared with other groups. Keywords: hydrofluoric acid etching, surface modification, micro-/nano-structures, osteogenic activity, titanium implant

Hongyu Sun,* Jing Zhou,* Zhu Huang,* Linlin Qu,* Ning Lin,* Chengxiao Liang, Ruiwu Dai, Lijun Tang, Fuzhou Tian General Surgery Center, Chengdu Military General Hospital, Chengdu, China *These authors contributed equally to this work Abstract: Carbon nanotubes (CNTs) provide an essential 2-D microenvironment for cardiomyocyte growth and function. However, it remains to be elucidated whether CNT nanostructures can promote cell–cell integrity and facilitate the formation of functional tissues in 3-D hydrogels. Here, single-walled CNTs were incorporated into collagen hydrogels to fabricate (CNT/Col) hydrogels, which improved mechanical and electrical properties. The incorporation of CNTs (up to 1 wt%) exhibited no toxicity to cardiomyocytes and enhanced cell adhesion and elongation. Through the use of immunohistochemical staining, transmission electron microscopy, and intracellular calcium-transient measurement, the incorporation of CNTs was found to improve cell alignment and assembly remarkably, which led to the formation of engineered cardiac tissues with stronger contraction potential. Importantly, cardiac tissues based on CNT/Col hydrogels were noted to have better functionality. Collectively, the incorporation of CNTs into the Col hydrogels improved cell alignment and the performance of cardiac constructs. Our study suggests that CNT/Col hydrogels offer a promising tissue scaffold for cardiac constructs, and might serve as injectable biomaterials to deliver cell or drug molecules for cardiac regeneration following myocardial infarction in the near future. Keywords: carbon nanotubes, collagen hydrogel, cardiac constructs, cell alignment, tissue functionality

Chongwen Wang,1,2,* Kehan Zhang,2,* Zhe Zhou,2,* Qingjun Li,2 Liting Shao,2 Rong Zhang Hao,3 Rui Xiao,2 Shengqi Wang1,2 1College of Life Sciences & Bio-Engineering, Beijing University of Technology, 2Beijing Key Laboratory of New Molecular Diagnosis Technologies for Infectious Diseases, Beijing Institute of Radiation Medicine, Beijing, 3Institute for Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, People's Republic of China *These authors contributed equally to this work Abstract: Nanomaterials combined with antibiotics exhibit synergistic effects and have gained increasing interest as promising antimicrobial agents. In this study, vancomycin-modified magnetic-based silver microflowers (Van/Fe3O4@SiO2@Ag microflowers) were rationally designed and prepared to achieve strong bactericidal ability, a wide antimicrobial spectrum, and good recyclability. High-performance Fe3O4@SiO2@Ag microflowers served as a multifunction-supporting matrix and exhibited sufficient magnetic response property due to their 200 nm Fe3O4 core. The microflowers also possessed a highly branched flower-like Ag shell that provided a large surface area for effective Ag ion release and bacterial contact. The modified-vancomycin layer was effectively bound to the cell wall of bacteria to increase the permeability of the cell membrane and facilitate the entry of the Ag ions into the bacterium, resulting in cell death. As such, the fabricated Van/Fe3O4@SiO2@Ag microflowers were predicted to be an effective and environment-friendly antibacterial agent. This hypothesis was verified through sterilization of Gram-negative Escherichia coli and Gram-positive methicillin-resistant Staphylococcus aureus, with minimum inhibitory concentrations of 10 and 20 µg mL-1, respectively. The microflowers also showed enhanced effect compared with bare Fe3O4@SiO2@Ag microflowers and free-form vancomycin, confirming the synergistic effects of the combination of the two components. Moreover, the antimicrobial effect was maintained at more than 90% after five cycling assays, indicating the high stability of the product. These findings reveal that Van/Fe3O4@SiO2@Ag microflowers exhibit promising applications in the antibacterial fields. Keywords: antibiotic-resistant bacteria, surface area, biological properties, magnetic composites, Ag shell