Core–shell nanocarriers with direct cytosolic delivery for tumor targeting

Core–shell nanocarriers with direct cytosolic delivery for tumor targeting

ChinaNanomedicine Abstracts / Nanomedicine: Nanotechnology, Biology, and Medicine 12 (2016) 449–575 relaxation studies show that the longitudinal rel...

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ChinaNanomedicine Abstracts / Nanomedicine: Nanotechnology, Biology, and Medicine 12 (2016) 449–575

relaxation studies show that the longitudinal relaxivity (r1) of GON-AN (11.64 mM− 1 s− 1) and GON-AN-FA (10.83 mM− 1 s− 1) is much larger than that of the traditional positive MRI contrast agents, such as Magnevist (4.7 mM− 1 s− 1). The results of cell viability assays indicate that the GON-AN and GON-AN-FA are almost non-cytotoxic. Furthermore, the specificities of GON-AN and GON-AN-FA were evaluated with two kinds of cancer cells that overexpress folate receptor alpha (FRα). The results reinforce that the GON-AN-FA is high-specifically-targetable to cancer cells via recognition of ligand FA and receptor FRα.1 In addition, the TEM and DLS results indicate that the SPION-AN-FA has a spherical shape, a uniform size and an excellent water-dispersibility (PDI b 0.05). The results of LSCM and flow cytometry demonstrate that the SPION-AN-FA is highly specific to MCF-7 and SPC-A1 cells due to the recognition of ligand FA and receptor FRα. The r1/r2 value of SPION-AN-FA is around 40, which is much higher than that of Resovist® indicating that our SPION-AN-FA has a stronger T2 shortening effect. The T2weighted images of MCF-7 cells incubated with SPION-AN-FA are significantly darker than those of MCF-7 cells incubated with AN, indicating that our SPION-AN-FA has a strong MR imaging efficacy.

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The poly(2-(diethylamino)ethyl methacrylate)/palygorskite (PDEAEMA/ PAL) composite microspheres were facilely one-step fabricated via the palygorskite (PAL) particles-stabilized Pickering emulsion polymerization. The morphology, chemical structure and content of PDEAEMA/PAL composite microspheres were investigated by polarizing optical microscopy (POM), scanning electron microscopy (SEM), Fourier-transform infrared (FT-IR) spectroscopy X-ray diffraction (XRD) and thermal gravimetric analysis (TGA). The pH-responsive behavior of composite microspheres was studied by measuring their size at different pH values. In addition, their release behavior was investigated using rhodamine B (RhB) as a model drug. It was proven that the release properties of RhB from PDEAEMA/PAL composite microspheres could be controlled by adjusting the pH values. The study of release kinetics found that Higuchi model was fit for RhB release from PDEAEMA/PAL composite microspheres at pH 5.0, 7.4 and 10.0, suggesting a mainly diffusion-controlled process. This kind of pH-sensitive materials may have potential applications in the controlled release of dyes, drugs and farm chemicals.

http://dx.doi.org/10.1016/j.nano.2015.12.132

Controllable fabrication and characterization of metal nanomaterials with specific surface properties for enhanced ionizing radiation Ningning Maa, Chao Maa,b, Hongyin Wanga, Peiyong Fenga, Xiaodong Zhanga, Nongyue Hea, Zhan Chenc, Fu-Gen Wua,⁎, aState Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, P.R. China, bSchool of Chemistry and Life Science, Guangdong University of Petrochemical Technology, Maoming, P.R. China, cDepartment of Chemistry, University of Michigan, Ann Arbor, MI, USA ⁎Corresponding author. E-mail address: [email protected] (F.-G. Wu) Metal nanomaterials like gold and silver are widely used as irradiation sensitizers in vitro due to their better biocompatibility and larger surface area to volume ratio. However, the specific mechanism with regard to enhanced ionizing radiation is largely unknown and widely variant from study to study. To further explore sensitizing properties based on different metal nanomaterials, we successfully synthesized three different types of nanomaterials with ultrafine surface construction and properties such as hollow gold nanospike, rough platinum nanoparticle and gold–silver nanoalloy. As-synthesized nanomaterials were characterized by transmission electron microscopy, scanning electronic microscopy and UV–vis absorption spectrum. Hollow gold nanospike and platinum nanoparticles exhibited special photometric characteristic due to the small grain size-distribution and rough surface performances. Gold–silver nanoalloy also formed typical core–shell structure. Furthermore, three types of metal nanomaterials present better radiation sensitizing properties in KB cells (human oral epithelial carcinoma) radiotherapy. These investigations could provide an effective strategy for tumor radiation therapy based on biocompatible metal radiation sensitizer. http://dx.doi.org/10.1016/j.nano.2015.12.133

Controlled release behavior of pH-sensitive poly(2-(diethylamino)ethyl methacrylate)/palygorskite composite microspheres prepared via pickering emulsion polymerization Xiaoxiao Tiana, Jia Lua,b, Jie Wua, Jing Chena, Yeling Jina, Tao Hua, Youqing Shenc, Shijie Dinga,⁎, aCollege of Life Science and Chemical Engineering, Huaiyin Institute of Technology, Huaian, China, bWuxi Waterworks Co., Ltd., Wuxi, China, cDepartment of Chemical and Biological Engineering, Zhejiang University, Hangzhou, China ⁎Corresponding author. E-mail addresses: [email protected] (Y. Shen), [email protected] (S. Ding)

http://dx.doi.org/10.1016/j.nano.2015.12.134

Core–shell nanocarriers with direct cytosolic delivery for tumor targeting Zhu Jin1, Wei He1, Yaqi Lv, Hui Cao, Jing Yao, Jianping Zhou, Lifang Yin⁎, State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, PR China. ⁎Corresponding author. 1 Contributed equally to this work. E-mail address: [email protected] (L. Yin) Low drug loading and premature burst release are inherent drawbacks of conventional nanoparticles, resulting in poor therapy outcome. Herein, biocompatible core–shell nanocarriers (NCs), based on nanoemulsiontemplates stabilized by β-lactoglobulin, with high drug payload were prepared to enhance the antitumor activities of chemotherapy agents with poor water solubility. Importantly, the NCs could directly penetrate the cell membrane and enter the cytosol, without entrapment within the endosomal-lysosomal system via the lipid raft-like pathway. Improved in vitro and in vivo tumor targeting and penetration were observed with paclitaxel (PTX)-loaded NCs and iRGD-NCs; the latter exhibited better antitumor activity because iRGD, a cell-penetrating peptide that binds to the αvβ3 integrin, enhances the accumulation and penetration of NCs in tumors. The NCs are cytocompatible, histocompatible, and non-toxic to other healthy tissues. In conclusion, the present nanocarriers with high drug-loading capacity and direct cytosolic delivery represent an efficient tumor-targeting drug delivery system with promising potential for cancer therapy.

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ChinaNanomedicine Abstracts / Nanomedicine: Nanotechnology, Biology, and Medicine 12 (2016) 449–575

Core–shell hybrid upconversion nanoparticles for upconversion luminescence and magnetic resonance dual-modality imaging Chuan Chena, Ning Kangb, Lei Rena,b, Xiangqun Guoa, aState Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, P.R. China, bDepartment of Biomaterials, College of Materials, Xiamen University, Xiamen, P.R. China E-mail address: [email protected] (L. Ren)

http://dx.doi.org/10.1016/j.nano.2015.12.135

Core–shell structure germanium nanowire ARRAYS for highly sensitive detection of cancer biomarker Qi Cai, Lin Ye, Baojian Xu, Zengfeng Di, Qinghui Jin, Jianlong Zhao, State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, China E-mail address: [email protected] (Q. Cai) MicroRNAs (miRNAs) have been regarded as promising biomarkers for the clinical diagnosis and prognosis of early-stage in different human cancers. Simultaneously, germanium (Ge) has attracted significant interest as a good candidate to replace silicon (Si) for future generation microelectronics, owing to better electronic properties. In this report, arrays of controllable, highly ordered germanium nanowire (GeNW) were fabricated by combining the complementary metal-oxide semiconductor (CMOS) compatible technology and Ge-condensation technology, and their biosensor applications in detection of lung cancer biomarker miRNA125a were investigated. A silicon/ germanium-on-insulator (SGOI) wafer with a ~100 nm Si0.7Ge0.3 layer was firstly patterned and etched, and the obtained fin structures were oxidized and annealed to realize Ge-SiO2 core–shell structure NW arrays. Based on the nanostructure, the GeNW arrays were modified with silanization and after covalently bonded with DNA probes, the nanosensor showed highly sensitive concentration-dependent conductance change in response to target miRNA125a. With this new method, controllable, highly ordered GeNW arrays were obtained, which were uniform with 200 nm width and 75 nm diameter, and surrounded by 60-nm-thick SiO2. Moreover, the nanosensor revealed high sensitivity for rapid and reliable detection of target miRNA125a, which was linear over a large dynamic range with a detection limit of 50 fM and high specificity in one-base mismatched miRNA sequences. This work demonstrated that an effective, compatible approach to obtain high-quality GeNW and the application in cancer biomarker detection may pave the way in the further development of GeNW in bioelectronics.

Figure 1. Schematic illustration of core–shell germanium nanowire arrays transistor for microRNA sensing (left). Characterization of GeNW including SEM, TEM and Raman spectra (upper right), and the biosensor application in micRNA125a detection (lower right).

http://dx.doi.org/10.1016/j.nano.2015.12.136

As medical science and technology developed in recent years, early diagnosis and treatment of diseases are becoming more and more desirable than before. Single imaging technique used for diagnosis, including magnetic resonance imaging (MRI), ultrasound, X-ray computed tomography (CT), positron emission tomography (PET), single-photon emission CT (SPECT) and optical imaging technologies, is usually insufficient to provide enough information for precise early medical diagnosis and effective therapy of various diseases. To overcome this shortage and incorporate the advantages of different imaging tools, increasing attention has been focused on developing multimodal nanoprobes using combined imaging modalities. Nitroxide radicals, such as 2,2,6,6-tetramethylpiperidine 1-Oxyl (TEMPO) and its derivatives, have recently been used as contrast agents for magnetic resonance imaging (MRI) and electron paramagnetic resonance imaging (EPRI). However, their rapid oneelectron bioreduction to diamagnetic N-hydroxy species when administered intravenously has limited their use in in vivo applications. In this article, a new approach of silica coating for carrying stable radicals was proposed. 4-CarboxylTEMPO nitroxide radical was covalently linked with 3-aminopropyltrimethoxysilane to produce a silanizing TEMPO radical. Utilizing a facile reaction based on the copolymerization of silanizing TEMPO radical with tetramethy orthosilicate in reverse microemulsion, a TEMPO radicals doped SiO2 nanostructure was synthesized and coated on the surface of NaYF4:Yb,Er/NaYF4 upconversion nanoparticles (UCNPs) to generate a novel multifunctional nanoprobe, PEGylated UCNP@TEMPO@SiO2 for upconversion luminescence (UCL) and magnetic resonance dual-modality imaging. The electron spin resonance (ESR) signals, generated by the TEMPO@SiO2 show an enhanced reduction resistance property for a period of time up to 1 h even in the present of 5 mM ascorbic acid. The longitudinal relaxivity of PEGylated UCNPs@TEMPO@SiO2 nanocomposites is about 10 times stronger than that for free TEMPO radicals. The core–shell NaYF4:Yb,Er/NaYF4 UCNPs synthesized by a modified user-friendly one-pot solvothermal strategy show a significant enhancement of UCL emission up to 60 times than the core NaYF4:Yb,Er. Furthermore, the PEGylated UCNP@TEMPO@SiO2 nanocomposites were further used as multifunctional nanoprobes to explore the performance in the UCL imaging of living cells and T1-weighted MRI in vitro and in vivo. http://dx.doi.org/10.1016/j.nano.2015.12.137

Crosslinked chitosan coated n-HA/PA66 scaffolds with controlled drug release capability for bone tissue engineering application Qin Zoua, Junfeng Lib, Yi Zuoa, Yubao Lia, aResearch Center for NanoBiomaterials, Analytical & Testing Center, Sichuan University, Chengdu, Sichuan, China b Institute of Material Science and Technology, Chengdu University of Technology, Chengdu, Sichuan, China E-mail address: [email protected] (Q. Zou) The objective of this study is to develop a simple and useful method for fabricating three-dimensional scaffolds with desirable drug delivering property. Previously, nano-hydroxyapatite/polyamide 66 (n-HA/PA66) composite porous scaffolds (group 1) were used as the matrix and coated with homogenously chitosan layer (group 2), and vanillin ((4-hydroxy-3-methoxybenzaldehyde) a popular flavor extracts broadly used in food) is chosen to crosslink the chitosan layer (group 3) (Figure 1, A). After coating, the scaffolds still have high levels of pore size and interconnectivity (Figure 1, B and C). Berberine (antibiotic drug) is designed to incorporate into the chitosan layer. After crosslinking, the drug release (Figure 1, D) of group C is obvious slower than group A (group 1 dipped into berberine The authors acknowledge the financial support of China NSFC project (No. 31370971) and Sichuan project (No. 2012FZ0125).