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Xuejiao Zhang, Lei Lei, Haiyan Zhang, Siyu Zhang, Weiwei Xing, Jin Wang, Haibo Li, Qing Zhao, Baoshan Xing
Attention has been paid to the environmental distribution and fate of nanomedicines. However, their effects on the toxicity of environmental pollutants are lack of knowledge. In this study, the negatively charged poly (ethylene glycol)-b-poly (L-lactide-co-glycolide) (mPEG-PLA) and positively charged polyethyleneimine-palmitate (PEI-PA) nanomicelles were synthesized and served as model drug carriers to study the interaction and combined toxicity with dichlorodiphenyltrichloroethane (DDT). DDT exerted limited effect on the biointerfacial behavior of mPEG-PLA nanomicelles, whereas it significantly mitigated the attachment of PEI-PA nanomicelles on the model cell membrane as monitored by quartz crystal microbalance with dissipation (QCM-D)...
June 7, 2018: Environmental Pollution
Xiaobo Jia, Yihua Zhang, Yu Zou, Yao Wang, Dechao Niu, Qianjun He, Zhangjian Huang, Weihong Zhu, He Tian, Jianlin Shi, Yongsheng Li
Chemotherapy suffers numbers of limitations including poor drug solubility, nonspecific biodistribution, and inevitable adverse effects on normal tissues. Tumor-targeted delivery and intratumoral stimuli-responsive release of drugs by nanomedicines are considered to be highly promising in solving these problems. Compared with traditional chemotherapeutic drugs, high concentration of nitric oxide (NO) exhibits unique anticancer effects. The development of tumor-targeting and intratumoral microenvironment-responsive NO-releasing nanomedicines is highly desired...
June 11, 2018: Advanced Materials
Jingjing Sun, Lingyi Sun, Jianchun Li, Jieni Xu, Zhuoya Wan, Zubin Ouyang, Lei Liang, Song Li, Dexing Zeng
Multifunctional nanoplatforms offering simultaneous imaging and therapeutic functions have been recognized as a highly promising strategy for personalized nanomedicine. In this work, we synthesized a farnesylthiosalicylate (FTS, a nontoxic Ras antagonist) based triblock copolymer POEG-b-PVBA-b-PFTS (POVF) composed of a poly(oligo(ethylene glycol) methacrylate) (POEG) hydrophilic block, a poly(FTS) hydrophobic block, and a poly(4-vinylbenzyl azide) (PVBA) middle block. The POVF polymer itself was active in inhibiting the tumor growth in vitro and in vivo...
June 6, 2018: Acta Biomaterialia
Bin Xu, Yuanjun Zhu, Cheng-Han Wang, Chong Qiu, Jing Sun, Yi Yan, Xin Chen, Jian-Cheng Wang, Qiang Zhang
Here the novel pH-responsive nanomicelles self-assembled with amphipathic meo-poly(ethylene glycol)-b-poly(L-histidine)-b-polyethylenimine (mPEG-b-PHis-b-PEI, EHE) copolymers based on hydrophobic interaction of PHis with deprotonation of imidazoles were developed for siRNA transfection. The cationic nanomicelles could electrostatically compact siRNA into stable EHE/siRNA nanoplexes with hydrodynamic diameter of ~190 nm and present low toxicity in normal physiological condition (pH~7.4). Different from pH-irresponsive ECE/siRNA nanoplexes based on mPEG-b-PCL-b-PEI, the EHE/siRNA nanoplexes exhibited a higher cellular uptake along with an increased zeta potential (from +18mV to +32mV) when the pH changed from 7...
June 8, 2018: ACS Applied Materials & Interfaces
Hongxue Shen, Dandan He, Shuxia Wang, Pinggang Ding, Jianan Wang, Jianming Ju
Genistein (GEN) is a natural dietary isoflavone, has been reported to show anticancer activities. However, its poor aqueous solubility and oral bioavailability limit its clinical application. We designed a novel genistein-loaded mixed micelles (GEN-M) system composed of Soluplus® and Vitamin E d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) were prepared by organic solvent evaporation aimed to overcome the challenges of GEN's poor solubility and then further improve its oral bioavailability. The optimized, spherical-shaped GEN-M was obtained at a ratio of 10:1 (Soluplus® :TPGS)...
May 31, 2018: Drug Development and Industrial Pharmacy
Amanpreet Kaur, Kiran Jyoti, Ashish Baldi, Upendra Kumar Jain, Ramesh Chandra, Jitender Madan
In present investigation, self-assembled nanomicelles of amphiphilic clotrimazole glycyl-glycine (CLT-GG-SANMs) analogue were customized for augmenting drug delivery, permeability and apoptosis in B16F1 mouse melanoma cancer cells both in vitro and in vivo following intratumoral (i.t.) route of administration. The mean particle size of CLT-GG-SANMs was measured to be 35.9 ± 3.4 nm in addition to zeta-potential of -17.1 ± 3.5 mV. The shape of CLT-GG-SANMs was visualized to be smooth and spherical as like nanoparticles...
August 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
Weihong Guo, Lizhi Deng, Jiang Yu, Zhaoyu Chen, Yanghee Woo, Hao Liu, Tuanjie Li, Tian Lin, Hao Chen, Mingli Zhao, Liming Zhang, Guoxin Li, Yanfeng Hu
Drug resistance is the major challenge facing cancer chemotherapy and nanoscale delivery systems based on natural materials, such as sericin, are a promising means of overcoming drug resistance. Yet, no attempt of introducing synthetic poly(γ-benzyl-L-glutamate) (PBLG) onto sericin polypeptide to fabricate a facile biocompatible and biodegradable micelle has been tried. Here, we prepared a polypeptide-based amphiphilic polymer containing hydrophilic sericin polypeptide backbone and PBLG side chains via ring-opening polymerization (ROP) strategy...
November 2018: Drug Delivery
Faisal Usman, Ruqaiya Khalil, Zaheer Ul-Haq, Titpawan Nakpheng, Teerapol Srichana
We report nanomicelles of amphotericin B (AmB) using various molar ratios of AmB and sodium deoxycholate sulfate (SDCS) for inhalation with improved stability, solubility, bioactivity, and safety. The particle sizes of all aerosolized formulations are expressed as mass median aerodynamic diameter (0.9-1.6 μm), fine particle fraction (70.3-86.5%), and geometric standard deviation (1.4-2.1) which indicated their sizes are appropriate for use as an inhaler. In vitro cytotoxicity studies conducted using respiratory and kidney cell lines demonstrated that the marketed Fungizone® was toxic to macrophage and embryonic kidney cells and cell viability decreased from 96 to 48% and from 97 to 67%, respectively when the AmB equivalent concentration was increased from 1 to 16 μg/mL...
April 24, 2018: AAPS PharmSciTech
Zhaoxian Wang, Samaresh Sau, Hashem O Alsaab, Arun K Iyer
Triple negative breast cancer (TNBC) is a highly aggressive tumor subtype, lacking estrogen, progesterone and human epidermal growth factor-2 (HER-2) receptors. Thus, early detection and targeted therapy of TNBC is an urgent need. Herein, we have developed a CD44 targeting Hyaluronic Acid (HA) decorated biocompatible oligomer, containing FDA approved vitamin E TPGS and Styrene Maleic Anhydride (SMA) (HA-SMA-TPGS) for targeting TNBC. The self-assembling HA-SMA-TPGS was encapsulated with poorly water soluble, potent curcumin analogue (CDF) to form nanomicelles (NM), HA-SMA-TPGS-CDF has demonstrated excellent nanoparticle characteristics for parenteral delivery...
April 17, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
Lan Tang, Lulu Fu, Zhuanfeng Zhu, Yan Yang, Boxuan Sun, Weiguang Shan, Zhenhai Zhang
Polymer nanoparticles modified with collagen peptides (CPs) are an attractive strategy for the oral delivery of active ingredients from Chinese medicine. Thus, in the present study, collagen cationic CPs were simply separated using ion-exchange resin from bovine CPs, to modify mixed nanomicelles (MMs) on the surface to improve the oral bioavailability of Cucurbitacin B (CuB). The physicochemical property of micelles was characterized, which confirmed the successful modification of the nanomicelles. CPs-modified nanomicelles in vitro were found to significantly increase cellular uptake and transportation...
January 1, 2018: Drug Delivery
Abanoub S Sedeky, Islam A Khalil, Amr Hefnawy, Ibrahim M El-Sherbiny
Brain tumor has a low prognosis with only 15% survival rate (5 years after diagnosis). Many of the current therapeutics have limited activity due to their inability to cross the blood brain barrier which retards drug accumulation in tumor site and causes drug resistance. Piperine, a phytochemical drug with poor solubility, could be an alternative to current therapeutics after evading its solubility and permeability limitations. Piperine micellization was optimized to improve drug solubility. Positively charged trimethyl-chitosan was synthesized then electrostatically adsorbed onto piperine nanomicelles forming core-shell nanoparticles...
June 15, 2018: European Journal of Pharmaceutical Sciences
Yaqin Zhu, Yu Jiang, Fenghua Meng, Chao Deng, Ru Cheng, Jian Zhang, Jan Feijen, Zhiyuan Zhong
Glioma is a highly challenging human malignancy as drugs typically exhibit a low blood-brain barrier (BBB) permeability as well as poor glioma selectivity and penetration. Here, we report that tandem nanomicelles co-functionalized with brain tumor-targeting and cell-penetrating peptides, Angiopep-2 and TAT, enable a highly efficacious and specific anti-glioma chemotherapy. Interestingly, tandem nanomicelles with 20 mol% Angiopep-2 and 10 mol% TAT linked via long and short poly(ethylene glycol)s, respectively, while maintaining a high glioma cell selectivity display markedly enhanced BBB permeation, glioma accumulation and penetration, and glioma cell uptake...
May 28, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Yi Zhang, Jielin Pan, Qilan Xu, Hao Li, Jianhao Wang, Chao Zhang, Guobin Hong
Objective: To construct carcinoma vascular endothelial-targeted polymeric nanomicelles with high magnetic resonance imaging (MRI) sensitivity and to evaluate their biological safety and in vitro tumor-targeting effect, and to monitor their feasibility using clinical MRI scanner. Method: Amphiphilic block copolymer, poly(ethylene glycol)- b -poly(ε-caprolactone) (PEG-PCL) was synthesized via the ring-opening polymerization of ε-caprolactone (CL) initiated by poly(ethylene glycol) (PEG), in which cyclic pentapeptide Arg-Gly-Asp (cRGD) was conjugated with the terminal of hydrophilic PEG block...
2018: International Journal of Medical Sciences
Juan Li, Yang Du, Zhenqi Jiang, Yuchen Tian, Nianxiang Qiu, Yinjie Wang, Muhammad Zubair Lqbal, Menying Hu, Ruifen Zou, Lijia Luo, Shiyu Du, Jie Tian, Aiguo Wu
Due to the molecular and cellular heterogeneity of glioma, discovery of novel targeted sites and ligands for glioma imaging and therapy remains challenging. Neuropeptide Y (NPY) Y1 receptors (Y1Rs) are highly over expressed in various brain tumors including glioma, and can serve as potential targeting sites for glioma imaging and therapy. Here, we show by in vivo fluorescent imaging that a highly selective Y1R ligand, [Asn6, Pro34] NPY (AP-NPY), facilitated circumvention of the blood brain barrier (BBB) by nanomicelles specifically targeting glioma...
March 29, 2018: Nanoscale
Li-Xuan Cai, Shao-Chuan Li, Dan-Ni Yan, Li-Peng Zhou, Fang Guo, Qing-Fu Sun
Transformations within container-molecules provide a good alternative between traditional homogeneous and heterogeneous catalysis, as the containers themselves can be regarded as single molecular nanomicelles. We report here the designed-synthesis of a water-soluble redox-active supramolecular Pd4 L2 cage and its application in the encapsulation of aromatic molecules and polyoxometalates (POMs) catalysts. Compared to the previous known Pd6 L4 cage, our results show that replacement of two cis-blocked palladium corners with p-xylene bridges through pyridinium bonds formation between the 2,4,6-tri-4-pyridyl-1,3,5-triazine (TPT) ligands not only provides reversible redox-activities for the new Pd4 L2 cage, but also realizes the expansion and subdivision of its internal cavity...
April 11, 2018: Journal of the American Chemical Society
Rui-Jun Ju, Li-Min Mu, Xue-Tao Li, Cui-Qing Li, Zhan-Jie Cheng, Wan-Liang Lu
The efficacy of anticancer drugs is rather limited in the treatment of brain glioma due to the hindrance of the blood-brain barrier (BBB). Herein, we reported an easy formulation of functional docetaxel nanomicelles for the treatment of brain glioma using a graft copolymer soluplus as basic material through dual-modifications with a glucose-lipid derivative and a dequalinium-lipid derivative. The studies were performed on brain glioma U87MG cells, in vitro BBB models and brain glioma-bearing nude mice. The functional docetaxel nanomicelles were approximately 100 nm...
March 8, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Martin P Andersson, Fabrice Gallou, Piyatida Klumphu, Balaram S Takale, Bruce H Lipshutz
Using density functional theory and the COSMO-RS implicit solvent model, we predict the structure and physical chemical properties of nanomicelles derived from the designer surfactant TPGS-750-M used in organic synthesis. We predict that the influence of chain length of the PEG region is low, while the termination of the PEG chain (-OH vs.-OCH3 ) plays a very large role. The interfacial tension is considerably lower between the micellar and water phases for the -OH than the -OCH3 terminated surfactant, and our calculations reproduce the large difference observed in average particle size as a function of PEG chain termination...
May 7, 2018: Chemistry: a European Journal
Alexandra Bukchin, Guillem Pascual-Pasto, Maria Cuadrado-Vilanova, Helena Castillo-Ecija, Carles Monterrubio, Nagore G Olaciregui, Monica Vila-Ubach, Laia Ordeix, Jaume Mora, Angel M Carcaboso, Alejandro Sosnik
We report for the first time on a nano-drug delivery system based on glucosylated polymeric nanomicelles to actively target the second-generation tyrosine kinase inhibitor dasatinib to glucose-avid pediatric sarcomas by the intravenous route. After a comprehensive physicochemical characterization that confirmed the substantially lower critical micellar concentration and the higher encapsulation capacity of the glucosylated amphiphilic nanocarrier with respect to the pristine counterpart, we showed a 9-fold decrease of the half maximal inhibitory concentration of dasatinib in a rhabdomyosarcoma cell line, Rh30, in vitro...
April 28, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Chenxi Qu, Jizhao Li, Yejuan Zhou, Shudi Yang, Weiliang Chen, Fang Li, Bengang You, Yang Liu, Xuenong Zhang
Low accumulation in tumor sites and slow intracellular drug release remain as the obstacles for nanoparticles to achieve effective delivery of chemotherapeutic drugs. In this study, multifunctional micelles were designed to deliver doxorubicin (Dox) to tumor sites to provide more efficient therapy against hepatic carcinoma. The micelles were based on pH-responsive carboxymethyl chitosan (CMCh) modified with a reactive oxygen species (ROS)-responsive segment phenylboronic acid pinacol ester (BAPE) and an active targeted ligand CD147 monoclonal antibody...
February 23, 2018: AAPS Journal
Dewen Leng, Jun Hu, Xiaolong Huang, Wei He, Yuan Wang, Mei Liu
Initiation and recurrence of lung cancer, the most fatal cancer worldwide, are attributed to lung cancer stem cells (CSCs). Evidence suggests that cancer cells can be turned into CSCs in a spontaneous way, and therefore simultaneous elimination of lung CSCs and cancer cells is crucial to achieve effective therapy of lung cancer. In lung cancer, epidermal growth factor receptor (EGFR) is overexpressed in both CSCs and cancer cells. The present study developed salinomycin poly(ethylene glycol) 2000-distearoylphosphatidylethanolamine nanomicelles conjugated with EGFR aptamers (M-SAL-EGFR) to kill lung CSCs and cancer cells...
August 1, 2018: Journal of Nanoscience and Nanotechnology
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