ONE-POT synthesis of magnetite-loaded dual mesoporous silica spheres for T2-weighted magnetic resonance imaging and drug delivery

ONE-POT synthesis of magnetite-loaded dual mesoporous silica spheres for T2-weighted magnetic resonance imaging and drug delivery

532 ChinaNanomedicine Abstracts / Nanomedicine: Nanotechnology, Biology, and Medicine 12 (2016) 449–575 Figure 3. Confocal laser scanning microscopy...

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

Figure 3. Confocal laser scanning microscopy photograph of Caco-2 cells monolayers after incubated with selected formation of fluorescently.

http://dx.doi.org/10.1016/j.nano.2015.12.237

Novel stimuli-responsive block copolymers as nonviral gene delivery vectors for efficiently overcoming physiologic barriers Zhishen Ge⁎, Junjie Li, Yang Li, CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui, China ⁎Corresponding author. E-mail address: [email protected] (Z. Ge) Gene therapy is a promising technique to treat a lot of intractable diseases and received great attention. Considering the safety issue of viral gene delivery vectors, design of safe and efficient nonviral ones is a critical issue for safe and successful gene therapy. Traditional nonviral gene carriers show relatively low transfection efficiency in systemic gene delivery failing to efficiently overcome extra- and intracellular barriers. Polyplex micelles based on stimuli-responsive block copolymers sensitive to disease or intracellular microenvironment showed great potentials to overcome physiologic barriers. We have constructed matrix metalloproteinase (MMP)-responsive and mixed block copolymers for efficient in vivo gene delivery. MMP-responsive polyplex micelles were prepared from GPLGVRG peptidelinked block copolymer, PEG-GPLGVRG-PAsp(DET) (PAsp(DET): poly{N[N-(2-aminoethyl)-2-aminoehtyl]aspartamide}). In the presence of MMP-2, the PEG layer of the polyplex micelles can be cleaved effectively exposing the positively charged cores, which resulted in higher association with cell membranes, improved cellular uptake, and efficient endosomal escape. This intelligent gene delivery system could overcome the PEG dilemma achieving not only PEG shielding for long circulation in the blood stream but also dePEGylation in response to MMP for higher cellular uptake and effective endosomal escape. This MMP-responsive polyplex micelle was more efficient in solving extracellular and intracellular barriers, which is a promising gene delivery vector candidate for systemic cancer gene therapy in tumors highly expressing MMP. We prepared mixed polyplex micelles (MPMs) from PEG-b-PAsp(DET) and poly(N-isopropylacrylamide)-b-PAsp(DET)] containing heterogeneous coronas with hydrophobic and hydrophilic microdomains coexisting could be obtained upon heating from 25 to 37 °C, which showed high tolerability against nuclease and strong resistance toward protein adsorption. The gene transfection efficiency of MPMs in nucleus pulposus (NP) cells was significantly higher than that of regular polyplex micelles prepared from sole block copolymer of PEG-b-PAsp(DET) (SPMs) in in vitro and in vivo evaluation due to the synergistic effect of improved colloidal stability and low cytotoxicity. High expression of heme oxygenase-1 (HO-1) in NP cells transfected by MPMs loading HO-1 pDNA was explored to treat disk degeneration induced by stab injury. Administration of HO-1 pDNA carried by MPMs in rat tail discs achieved better therapeutic efficacy. Thus, MPMs loading HO-1 pDNA were demonstrated to be potential as a safe and highefficiency nonviral gene delivery system for retarding or regenerating the degenerative discs.

http://dx.doi.org/10.1016/j.nano.2015.12.238

“Off–On” switchable sensor: A near-infrared fluorescent pH probe and its imaging applications in vivo Xiaoqing Meng, Yalin Lv, Li Zhang, Ping Gong⁎, Lintao Cai⁎, CAS Key Laboratory of Health Informatics, Guangdong Key Laboratory of Nanomedicine, Shenzhen Key Laboratory of Cancer Nanotechnology, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, P.R. China ⁎Corresponding authors. E-mail address: [email protected] (L. Cai)

Intracellular or extracellular pH is influenced by diverse physiological and pathological processes, so quantitatively measuring pH is useful for cellular analysis or diagnosis. In this work, a new near-infrared (NIR) fluorescence turn-on probe CP utilizing a fluorophorespacer-receptor molecular framework that can modulate the fluorescence emission intensity through a fast photoinduced electron-transfer process was developed. Our strategy was to choose tricarbocyanine (Cy), an NIR fluorescent dye with high extinction coefficients, as a fluorophore, and N-(4-pyridylmethyl)ethylenediamine (Py) as a receptor. The pH titration indicated that CP can monitor the minor physiological pH fluctuations with a pKa of ∼6.40, which is valuable for intracellular pH researches and tumor diagnosis. The probe responds linearly and rapidly to minor pH fluctuations within the range of 5.00-7.50 and exhibits strong dependence on pH changes. As expected, the realtime imaging of cellular pH and the detection of pH in situ was achieved successfully in living A549 and HeLa cells by this probe. It is shown that the probe effectively avoids the influence of autofluorescence and native cellular species in biological systems and meanwhile exhibits high sensitivity, good photostability, low cytotoxicity and excellent cell membrane permeability. This fluorescence probe is further examined as tumor microenvironment-activatable probes for intravenous in vivo tumor imaging, which is expected to be of crucial importance for clinical tumor diagnostics.

http://dx.doi.org/10.1016/j.nano.2015.12.239

ONE-POT synthesis of magnetite-loaded dual mesoporous silica spheres for T2-weighted magnetic resonance imaging and drug delivery Xiaofeng Luo, Dechao Niu, Yongsheng Li⁎, Lab of Low-Dimensional Materials Chemistry, East China University of Science and Technology, Shanghai, China ⁎Corresponding author. E-mail address: [email protected] (Y. Li) Recently, integration of mesoporous silica nanoparticles (MSNs) and superparamagnetic nanocrystals to fabricate multifunctional platforms has great potential for simultaneous imaging and drug delivery. In this work, we have successfully developed a simple one-step approach to synthesize magnetite-loaded dual-mesoporous silica spheres consisting of large pores in the core and small pores in the shell ([email protected]) by embedding oil-soluble Fe3O4 into the larger pore channels of

Figure 1. (a) TEM image and plot of inverse transverse relaxation time (1/T2) versus Fe concentration of [email protected] (c) CLSM images of MCF-7 cells incubated with [email protected]@DMSSs (a) and [email protected]@DMSSs (b) for 4 h.

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

DMSSs. TEM result showed that the as-synthesized [email protected] possess monodispersity and well-defined core–shell structure (Figure 1, a). In addition, the loading amount of magnetite can be easily adjusted by varying the initial concentrations of the Fe3O4 magnetite nanoparticles in the oil phase. The in vitro test indicated that the [email protected] displayed excellent T2-weighted magnetic resonance (MR) imaging effect with a maximum T2 relaxivity (r2) of 421.5 mM−1 · s−1 (Figure 1, b). Furthermore, a high doxorubicin (DOX) loading capacity (65 wt%) was achieved and the obtained DOX-loaded [email protected] ([email protected]@DMSSs) exhibited pHsensitive behavior with accelerated release of DOX in acidic environment. Confocal laser scanning microscopy (CLSM) observation showed that the [email protected] was able to locate in the cytoplasm of MCF-7 cells and release DOX into the nucleus to kill cancer cells (Figure 1, c and d). In conclusion, the [email protected] are expected to be promising multifunctional candidates as both MR contrast agents and drug delivery carriers in further biomedical applications. http://dx.doi.org/10.1016/j.nano.2015.12.240

One-step quantitative detection of human chorionic gonadotropin by integrating immunochromatography test strip with fluorescence detection of quantum dots Xue Li, Yudong Wu, Yingyi Yao, Jian Zhang, Jin Chang⁎, School of Life Science, Tianjin University and Tianjin Key Laboratory of Composites and Functional Materials, Tianjin, P.R. China ⁎Corresponding author. E-mail address: [email protected] (J. Chang) During the past decade, a number of methods have been developed for tumor marker detection. Although lots of advances have been achieved, detection methods are still severely restricted by their time-consuming, low sensitivity and laborious process. Recently, a convenient, simple and powerful analysis is referred to as immunochromatography test strip (ICTS), which has attracted increasing attention. However, the limitations of sensitive and quantitative analysis severely hamper their application as a reliable medical testing in early detection of cancer bacause of the basis defective ICTS signal label. In order to overcome the limitations, quantum dots (QDs) are implored as an efficient fluorescent signal label into the ICTS system to generating high sensitive and efficient signal. In this work, we report on the development of a QDs based ICTS platform designed to provide fast and portable detection of protein biomarker, using HCG as a model analyte. HCG has been proved as a valuable biomarker for pregnancy. The effective reaction time, sensitivity, specificity and capability of quantitative detection of these QD s based ICTS were investigated to display its performance. As expected, a wellperforming biosensor was designed by combining the ICTS with QDs for the quantitative detection of HCG. This integration enables the ICTS to sensitively and specifically determine the concentration of HCG in 20 min. Under the optimized conditions, the detection limit was about 0.24 IU/L. There was a significant linear relationship between HCG concentration and fluorescence signal in the log–log plot with R2 = 0.994 (Figure 1). These results demonstrated the QDs-based ICTS was a rapid, sensitive, specific and low cost point-of-care diagnostic format. In view of its advantages, the new biosensors may be a nascent sensing technology that opens up new opportunities for the early detection of cancer at the site of patient care.

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“Optically active” graphene quantum dots by heavy atom effect Yan Lia, Zhiyong Wub, Haiqing Donga, Donglu Shia, Yongyong Lia,⁎, aShanghai East Hospital, The Institute for Biomedical Engineering & Nano Science (iNANO), Tongji University School of Medicine, Shanghai, PR China, bSchool of Material Science and Engineering, Tongji University, Shanghai, PR China ⁎Corresponding author. E-mail address: [email protected] (Y. Li) Photodynamic therapy (PDT) is currently an effective method that is widely used in the treatment of cancer. Nano-graphene oxide has been reported as the excellent nanocarrier of photosensitizers for improved PDT effect in our previous works as well as others. In these works, the graphene itself was physically inert as only a nanocarrier. Herein, we reported a type of “optically active” graphene quantum dots that were chemically designed with heavy atoms like iodine in their planar structure. The new system can improve the rate of singlet oxygen (1O2) production effectively by external heavy atom effect. Matrices containing heavy atoms have been found to enhance the spin-orbit coupling of a PS, and thus promote the intersystem crossing from the photoexcited singlet state of the PS to the photoexcited triplet state, leading to an improvement in the 1O2 yield and enhancement of PDT effect. The “optically active” graphene quantum dot (GQD) consists of a single atomic layer of nano-sized graphite. The unique graphene structure results in the excellent performances such as high surface area, large diameter and better surface grafting, making them ideal platforms for delivery of various bio-agents. More importantly, assisted by its unique aromatic structure, the heavy atom iodine was introduced on GQD by using a standard chloramine T oxidation method (Figure 1, a). This chemical treatment has little effect on the size and UV absorbance spectrum of the obtained I-GQD in comparison with GQD. However, a significant fluorescence spectrum was present, where the fluorescence intensity of I-GQD was reduced compared to that of GQD. Comparative studies with I-modified and unmodified GQD have demonstrated an external heavy atom effect on the encapsulated PS molecule chlorin e6 (Ce6) that significantly enhances the efficiency of 1O2 generation. As shown in Figure 1, b and c, the fluorescence emission spectra of SOSG associated with the generation rate of 1O2 of IGQD/Ce6 is more than twofold of that of GQD/Ce6.

Figure 1. (a) A synthetic scheme of I-GQD from GQD. Purple: carbon; red: oxygen; white: hydrogen; pink: iodine. (b) Time-dependent fluorescence emission spectra of SOSG by 1O2 generation of GQD/Ce6. (c) Timedependent fluorescence emission spectra of SOSG by 1O2 generation of I-GQD/Ce6.

http://dx.doi.org/10.1016/j.nano.2015.12.242

Figure 1. Fluorescence image (A) and calibration curve of the quantitative detection of HCG by the ICTS.

http://dx.doi.org/10.1016/j.nano.2015.12.241

Paclitaxel loaded human serum albumin nanoparticles stabilized with intermolecular disulfide bonds Shufang Zhao, Wentan Wang, Yanbin Huang⁎, Yuhang Fu, Yi Cheng⁎, Department of Chemical Engineering, Tsinghua University, Beijing, P.R. China ⁎Corresponding authors. E-mail address: [email protected] (Y. Cheng) Paclitaxel (PTX) is a major anticancer drug, which is highly efficient in treating many types of cancers. Since it is poorly soluble in water, surfactant and organic solvent are used in