Ning-Lin Zhou

Name: 周宁琳

Organization: Nanjing Normal University , China

Department: Jiangsu Engineering Research Center for Biomedical Function Materials

Title: Professor(PhD)

Chemicals
References

Near-infrared light triggered photo-therapy, in combination with chemotherapy using magnetofluorescent carbon quantum dots for effective cancer treating

Co-reporter:Ming Zhang, Wentao Wang, Ninglin Zhou, Ping Yuan, Yutian Su, Maoni Shao, Cheng Chi, Feiyan Pan

Carbon 2017 Volume 118(Volume 118) pp:

Publication Date(Web):1 July 2017

DOI:10.1016/j.carbon.2017.03.085

Magnetofluorescent carbon quantum dots (MCQDs) have attracted significant attention in biomedical studies due to their major role in cancer photothermal therapeutics. We synthesized the FeN@CQDs with intrinsic photoluminescent and magnetic properties with a green, hydrothermal method. These magnetofluorescent FeN@CQDs were conjugated with a folic acid and riboflavin (Rf-FA-FeN@CQDs) as the light-triggered theranostics for simultaneous photothermal therapy (PTT) and photodynamic therapy (PDT). In order to reduce Rf-FA-FeN@CQDs biological toxicity, we used a highly efficient cross-linking reaction to incorporate Rf-FA-FeN@CQDs nanostructures into polymer nanospheres. Doxorubicin, an anticancer drug, was further incorporated into the GP-Rf-FA-FeN@CQDs to form GP-Rf-FA-FeN@CQDs-DOX to enable targeted drug delivery. The uptake into cancer cells and the intracellular location of the GP-Rf-FA-FeN@CQDs-DOX were observed by confocal laser scanning microscopy. The results of both in vitro and in vivo experiments reveal that the developed can deliver anti-cancer drugs to target cells, release them intracellular upon NIR irradiation, and effectively eliminate tumors through chemo-photo synergistic therapeutic effect.Download high-res image (346KB)Download full-size image

pH-Sensitive N-doped carbon dots–heparin and doxorubicin drug delivery system: preparation and anticancer research

Co-reporter:Ming Zhang;Ping Yuan;Ninglin Zhou;Yutian Su;Maoni Shao;Cheng Chi

RSC Advances (2011-Present) 2017 vol. 7(Issue 15) pp:9347-9356

Publication Date(Web):2017/01/27

DOI:10.1039/C6RA28345D

In this study, doxorubicin (DOX) hydrochloride as a model drug, N-doped carbon dots as a drug carrier, and heparin as an auxiliary medicine were selected to design and prepare a multi-functional drug delivery system with pH-triggered drug release. The CDs were anchored onto heparin via chemical bonds and DOX was then loaded on CDs–Hep by taking advantage of the electrostatic interactions between DOX and CDs–Hep. The structures of all the intermediates and final products were characterized and confirmed by 1H NMR and FT-IR spectroscopies. The CDs–Hep/DOX drug delivery system exhibited good stability. However, in acidic buffer, Hep and DOX release rate was accelerated and it was pH-responsive. In vitro and in vivo studies confirmed the high biocompatibility and low-toxicity of the CDs. An MTT assay showed that inhibition rate of CDs–Hep/DOX for HeLa, MCF-7 and A549 cells was close to that of DOX, indicating that the prepared drug system has a higher toxicity for tumor cells and can achieve an effective therapeutic effect. This systemic evaluation suggests that the introduction of Hep improves blood compatibility. In addition, the internalization of CDs–Hep/DOX by A549 cells was further confirmed using laser scanning confocal microscopy. As a result, a therapy was achieved due to the incorporation of Hep and DOX.

Graphene oxide and adenosine triphosphate as a source for functionalized carbon dots with applications in pH-triggered drug delivery and cell imaging

Co-reporter:Ming Zhang;Ninglin Zhou;Ping Yuan;Yutian Su;Maoni Shao;Cheng Chi

RSC Advances (2011-Present) 2017 vol. 7(Issue 15) pp:9284-9293

Publication Date(Web):2017/01/27

DOI:10.1039/C6RA27887F

A folate-functionalized carbon dot-based nanocarrier system has been successfully synthesized for cancer cell targeted drug delivery. We hydrothermally synthesized blue photoluminescent N,P-CDs using adenosine triphosphate and graphene oxide as the starting materials. The particle size of the N,P-CDs was ca. 3.8 nm. An anticancer drug, doxorubicin (DOX), was grafted onto the carbon dots via electrostatic interactions, and a more specific anticancer agent (DOX/N,P-CDs) was obtained. The DOX/N,P-CDs were characterized by H-NMR, C-NMR and UV-vis analysis. In addition, the DOX/N,P-CDs showed a pH-dependent release and were easily absorbed by cells. When compared to DOX, DOX/N,P-CDs nanoparticles exhibited the same cytotoxicity towards human cervical cancer cells (HeLa cells) and human pulmonary adenocarcinoma cells (A549 cells). Hemolysis test results indicated that DOX/N,P-CDs were safe for blood-contact applications and were suitable for intravenous administration. Owing to their intrinsic biocompatibility, N,P-CDs can be used for cell imaging and drug delivery with excellent targeting property.

Preparation of fluorescent N,P-doped carbon dots derived from adenosine 5′-monophosphate for use in multicolor bioimaging of adenocarcinomic human alveolar basal epithelial cells

Co-reporter:Yutian Su;Ming Zhang;Ninglin Zhou;Maoni Shao;Cheng Chi;Ping Yuan

Microchimica Acta 2017 Volume 184( Issue 3) pp:699-706

Publication Date(Web):2017 March

DOI:10.1007/s00604-016-2039-5

Carbon quantum dots doped with nitrogen and phosphorus were prepared from adenosine 5′-monophosphate (AMP) in a single simple synthesis step. The nitrogen and phosphorus doped C-dots (N,P-C-dots) were characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, fluorescence spectroscopy, X-ray photoelectron spectroscopy and X-ray powder diffraction. These carbon dots display blue fluorescence, with excitation/emission maxima at 360/430 nm, a quantum yield of 26.5% and an average decay time of 4.3 ns. Fluorescence is strongest at neutral pH values but quenched at very high and very low pH values. It is also quenched by ferric ions which suggests the use of the N,P-C-dots as fluorescent probes for Fe(III). A hemolysis test inferred favorable blood compatibility. The fluorescence of the doped C-dots is excitation wavelength dependent and also is susceptible to 2-photon excitation. The nanoparticles were applied in the fluorescent multicolor bioimaging of A549 (adenocarcinomic alveolar basal epithelial) cells under different excitation wavelengths, typically at 405, 488 and 543 nm. Emission colors ranging from blue to green and red can be adjusted in this way.

N-Doped CDs–GP nanospheres as a drug delivery nanocarrier system with carbon dots and a fluorescent tracer

Co-reporter:Ping Yuan;Ming Zhang;Ninglin Zhou;Cheng Chi;Xiaohong Chu;Baohong Sun;Siying Feng

New Journal of Chemistry (1998-Present) 2017 vol. 41(Issue 19) pp:10880-10889

Publication Date(Web):2017/09/25

DOI:10.1039/C7NJ01762F

In this study, a carbon dots-genipin covalent conjugate (CDs–GP) was synthesized, characterized by Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), and fluorescence spectroscopy (FL). These carbon dots displayed three dimensional spherical structures with uniform diameters, blue fluorescence (excitation/emission maxima at 355/455 nm), and high water dispersion with a zeta potential of +17.1 mV. Moreover, the CDs–GP conjugate showed excellent biocompatibility with HeLa and A549 cells. Furthermore, the blood compatibility of CDs–GP was evaluated by hemolysis, and hemolysis rates were less than 5%. We deem that combining the outstanding properties of GP with CDs could further promote the development of CDs in biological applications, achieving multifunctional CDs with targeting, in vivo imaging and therapeutic-delivery capabilities. Our in vitro results demonstrated the high uptake of the CDs–GP by cells. Significantly, the prepared CDs–GP exhibited strong optical absorbance under 635 nm laser irradiation, thus the present research demonstrated that the prepared CDs–GP could be employed as a near infrared (NIR)-absorbing agent as well as a non-toxic drug carrier, realizing the synergistic treatment of photothermal therapy (PTT) and drug delivery. The release of heparin (Hep) could be selectively stimulated by NIR-light and low pH, enabling intracellular drug accumulation and thereby enhancing the efficiency. Overall, all these data suggest that the CDs–GP conjugate has a potential application as a drug delivery system and PTT agent.

Magnetic and fluorescent carbon nanotubes for dual modal imaging and photothermal and chemo-therapy of cancer cells in living mice

Co-reporter:Ming Zhang, Wentao Wang, Fan Wu, Ping Yuan, Cheng Chi, Ninglin Zhou

Carbon 2017 Volume 123(Volume 123) pp:

Publication Date(Web):1 October 2017

DOI:10.1016/j.carbon.2017.07.032

Multi-walled carbon nanotubes (MWCNTs) have drawn increasing attention in biomedical fields because of their unique structures and properties, including good photothermal performance, large surface areas, strong near-infrared (NIR) absorbance, and size stability on the nanoscale. However, big challenge for this platform is to achieve fluorescence/magnetic resonance (MR) imaging and photothermal therapy (PTT) therapy in single nanotube. In this work, Multi-walled carbon nanotubes-magnetofluorescent carbon quantum dots/doxorubicin nanocomposites was prepared. The nanocomposite was then used as carriers for targeted drug transport in cancer therapy. These nanocomposites possess high heat-generating ability, pH and NIR responsive drug delivery, and heat-induced high drug release as well. Experiments in vitro and in vivo show that this platform can deliver anti-cancer drugs to targeted cells, releasing them intracellular upon NIR irradiation, and eliminate tumors effectively through chemo/photothermal synergistic therapeutic effect. Based on the findings of this work, further development of using other CNTs as highly efficient NIR agents can be achieved for vivo tumor imaging and chemo/photothermal synergistic therapeutic.Schematic diagram showing the strategy for the synthesis and combined photothermal and chemo-therapy of GP-GdN@CQDs-MWCNTs/DOX-EGFR.Download high-res image (273KB)Download full-size image

Hydroxypropyl-β-cyclodextrin–graphene oxide conjugates: Carriers for anti-cancer drugs

Co-reporter:Jingting Tan, Na Meng, Yunting Fan, Yutian Su, Ming Zhang, Yinghong Xiao, Ninglin Zhou

Materials Science and Engineering: C 2016 Volume 61() pp:681-687

Publication Date(Web):1 April 2016

DOI:10.1016/j.msec.2015.12.098

•Hydroxypropyl-β-cyclodextrin (HP-β-CD) modified carboxylated graphene oxide (GO-COOH) was designed as a drug carrier.•The prepared PTX-loaded nanospheres can be dispersed in aqueous medium stably.•The GO-COO-HP-β-CD nanospheres are safe for blood-contact applications.•This newly developed PTX-delivery system could confer significantly improved cytotoxicity against tumor cells.A novel drug carrier based on hydroxypropyl-β-cyclodextrin (HP-β-CD) modified carboxylated graphene oxide (GO-COOH) was designed to incorporate anti-cancer drug paclitaxel (PTX). The formulated nanomedicines were characterized by Fourier transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM). Results showed that PTX can be incorporated into GO-COO-HP-β-CD nanospheres successfully, with an average diameter of about 100 nm. The solubility and stability of PTX-loaded GO-COO-HP-β-CD nanospheres in aqueous media were greatly enhanced compared with the untreated PTX. The results of hemolysis test demonstrated that the drug-loaded nanospheres were qualified with good blood compatibility for intravenous use. In vitro anti-tumor activity was measured and results demonstrated that the incorporation of PTX into the newly developed GO-COO-HP-β-CD carrier could confer significantly improved cytotoxicity to the nanosystem against tumor cells than single application of PTX. GO-COO-HP-β-CD nanospheres may represent a promising formulation platform for a broad range of therapeutic agent, especially those with poor solubility.

Synthesis and properties of PDMS/montmorillonite-cetyltrimethylammonium bromide-heparin films

Co-reporter:Na Meng, Ning-Lin Zhou

Carbohydrate Polymers 2014 Volume 105() pp:70-74

Publication Date(Web):25 May 2014

DOI:10.1016/j.carbpol.2014.01.052

•The PDMS/MMT-CTAB-HEP films were prepared by solution intercalation technique.•The mechanical properties of PDMS/2 wt% MMT-CTAB-HEP films were increased.•The PDMS/2 wt% MMT-CTAB-HEP film showed excellent hemocompatibility.In this study, poly(dimethylsiloxane)(PDMS)/montmorillonite-cetyltrimethylammonium bromide-heparin (PDMS/MMT-CTAB-HEP) films were prepared by solution intercalation technique. The cetyltrimethylammonium bromide-heparin (CTAB-HEP) was intercalated into montmorillonite (MMT) layers forming MMT-CTAB-HEP (modified MMT). The structure and properties of the film were characterized by XRD, TG and SEM.The modified MMT was homogeneously dispersed within the PDMS matrix. The effect of modified MMT on mechanical properties of the film was also investigated. As the modified MMT content was lower than 2 wt%, the films showed excellent mechanical properties. The blood compatibility of PDMS/MMT-CTAB-HEP films was further evaluated by hemolysis test and platelet adhesion. Both hemolysis and platelet adhesions tests showed that PDMS/MMT-CTAB-HEP film had better blood compatibility than pure PDMS.

Synthesis and characterization of poly(2-methacryloyloxyethyl phosphorylcholine) onto graphene oxide

Co-reporter:Suxing Jin;Ninglin Zhou;Dong Xu;Jian Shen

Polymers for Advanced Technologies 2013 Volume 24( Issue 7) pp:685-691

Publication Date(Web):

DOI:10.1002/pat.3148

The polyzwitterionic brushes comprised of poly(2-methacryloyloxyethyl phosphorylcholine) (pMPC) segments, which are used for surface modification of polymers and biocompatible coatings, were investigated. In this work, reverse surface-initiated atom transfer radical polymerization (RATRP) of zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) is employed to tailor the functionality of graphene oxide (GeneO) in a well-controlled manner and produce a series of well-defined hemocompatible hybrids (termed as GeneO-g-pMPC). The complexes were characterized by FT-IR, XRD, and Raman. Results show that MPC has been coordinated on the graphene oxide sheet. Thermal stability of the nanocomposites in comparison with the neat copolymer is revealed by thermogravimetric analysis and differential thermal analysis. Scanning electron microscopy and transmission electron microscope images of the nanoconposite displays pMPC chains were capable of existing on GeneO sheet by RATRP. The biocompatibility properties were measured by plasma recalcification profile tests, hemolysis test, and MTT assays, respectively. The results confirm that the pMPC grafting can substantially enhance the hemocompatibility of the GeneO particles, and the GeneO-g-pMPC hybrids can be used as biomaterials without causing any hemolysis. With the versatility of RATRP and the excellent hemocompatibility of zwitterionic polymer chains, the GeneO-g-pMPC nanoparticles with desirable blood properties can be readily tailored to cater to various biomedical applications. Copyright © 2013 John Wiley & Sons, Ltd.

Long-term and controlled release of chlorhexidine–copper(II) from organically modified montmorillonite (OMMT) nanocomposites

Co-reporter:Yue Wu, Ninglin Zhou, Wenhao Li, Hao Gu, Yunting Fan, Jiang Yuan

Materials Science and Engineering: C 2013 Volume 33(Issue 2) pp:752-757

Publication Date(Web):1 March 2013

DOI:10.1016/j.msec.2012.10.028

Drug/metal ion complexes exhibit improved antimicrobial activity and intercalating the above complexes into the interlayer of clay endows a long-term and controlled-release behavior. In this study, chlorhexidine was first complexed with copper (II) ion and then intercalated into the interlayer of MMT to form chlorhexidine–copper (II)/montmorillonite (CHX–Cu/MMT) nanocomposites. The nanocomposites were characterized with Fourier transform infrared (FT-IR), X-ray diffraction (XRD) and thermogravimetric analysis (TGA). A nearly lateral-monolayer arrangement of CHX–Cu was supposed for the intercalation. Release kinetics indicated that the release process satisfied a pseudo-second-order mode. The antibacterial results showed that the CHX–Cu/MMT composites had long-term and controlled-release behavior.The antibacterial agent of chlorhexidine was first complexed with copper(II) chloride and then intercalated into the interlayer of MMT to form nanocomposites. The CHX–Cu/MMT composites exhibited long-term antibacterial activity and controlled release behaviors.Highlights► Chlorhexidine–copper (II)/montmorillonite (CHX–Cu/MMT) complex exhibits improved antimicrobial activity. ► Intercalating chlorhexidine–copper (II) complex into the interlayer of clay endows a long-term and controlled-release. ► Release kinetics indicated that the release process satisfied a pseudo-second-order mode. ► A nearly lateral-monolayer arrangement of CHX–Cu was supposed for the intercalation.

Terbinafine hydrochloride intercalated in montmorillonite: synthesis and characterization

Co-reporter:Na Meng;Jian Shen

Research on Chemical Intermediates 2013 Volume 39( Issue 2) pp:671-680

Publication Date(Web):2013 February

DOI:10.1007/s11164-012-0588-8

The novel antifungal hybrid of terbinafine hydrochloride (TER-HCl)/montmorillonite was synthesized by the intercalation method under mechanical stirring. Intercalation of TER-HCl in the MMT galleries was characterized by X-ray diffraction (XRD), Fourier transform infrared spectra, elemental analysis (EA). and thermogravimetric analysis (TGA). The results from IR, TGA, and EA showed a difference in chemical composition of the MMT and the TER-HCl/MMT. XRD analysis showed that the basal spacing of montmorillonite significantly expanded from 1.53 to 2.79 nm. TER-HCl was successfully intercalated into the interlayer of MMT, and 28 % of TER-HCl was released after 48 h in 0.9 % (w/v) NaCl aqueous solution (pH 7) at 37 ± 0.5 °C. The antifungal activity of the hybrid against Candida albicans was evaluated using the inhibitory zone method and the minimum inhibitory concentration. The TER-HCl/MMT strongly inhibited C. albicans. These results show that TER-HCl/MMT can be useful in biomedical applications.

Preparation, characterization, and evaluation of a heparin-benzalkonium chloride-graphite oxide/polymethylvinyl siloxane nanocomposite

Co-reporter:Ninglin Zhou;Dong Xu;Jun Zhang;Yinchen Ma;Jiang Yuan;Jian Shen

Journal of Biomedical Materials Research Part A 2012 Volume 100A( Issue 6) pp:1623-1627

Publication Date(Web):

DOI:10.1002/jbm.a.34110

Abstract

A heparin (Hep)—benzalkonium chloride (C12)-graphite oxide (GO)/polymethylvinyl siloxane (PMVS) nancomposite was prepared via melting intercalation at different temperatures. Scanning electron microscopy images showed the Hep-C12-GO was well dispersed into PMVS processed at 100°C. Mechanical properties measurement demonstrated that the addition of Hep-C12-GO maintained its strength. XRD data indicated that Hep-C12-GO lost its layer structure completely. FTIR results suggested that Hep-C12-GO interacted with PMVS strongly. Antibacterial activity of resulting nanocomposite was evaluated using zone of inhibition and bacteria adhesion methods. The results demonstrated that Hep-C12-GO/PMVS had a good capability against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. Antithrombogenic properties were assessed using platelet adhesion experiment and the results showed that Hep-C12-GO/PMVS was blood-compatible. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 2012.

Evaluation of antithrombogenic and antibacterial activities of a graphite oxide/heparin–benzalkonium chloride composite

Co-reporter:Ninglin Zhou, Na Meng, Yinchen Ma, Xiangmin Liao, Jun Zhang, Li Li, Jian Shen

Carbon 2009 Volume 47(Issue 5) pp:1343-1350

Publication Date(Web):April 2009

DOI:10.1016/j.carbon.2009.01.025

A graphite oxide (GO)/heparin–benzalkonium chloride (C12) composite was synthesized. The composite was characterized by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). XRD data showed that spacing between layers of GO increased from 0.59 to 3.256 nm. This enlarged layer spacing suggested that heparin–C12 complex intercalated completely in between layers of GO. FTIR also confirmed intercalation of heparin–C12 complex into GO gallery. In vitro release rate of heparin from GO–heparin–C12 was monitored for 30 days. Heparin released at a very fast rate from the composite matrix in the first day. The release slowed down significantly after the first day and continued for 30 days. In addition, antibacterial activity of the composite against Escherichia coli (E. coli) and Staphlococcus aureus (S. aureus) was evaluated using zone of inhibition and colony count assays. Both GO–heparin–C12 and GO–C12 clearly showed antibacterial activity against E. coli and S. aureus while GO alone has a relatively low activity against S. aureus and almost no effect on E. coli.

Synthesis and antifungal activities of polymer/montmorillonite–terbinafine hydrochloride nanocomposite films

Co-reporter:Na Meng, Ning-Lin Zhou, Shuang-Quan Zhang, Jian Shen

Applied Clay Science (October 2009) Volume 46(Issue 2) pp:136-140

Publication Date(Web):October 2009

DOI:10.1016/j.clay.2009.07.003

Synthesis and antimicrobial activities of polymer/montmorillonite–chlorhexidine acetate nanocomposite films

Co-reporter:Na Meng, Ning-Lin Zhou, Shuang-Quan Zhang, Jian Shen

Applied Clay Science (January 2009) Volume 42(Issues 3–4) pp:667-670

Publication Date(Web):January 2009

DOI:10.1016/j.clay.2008.06.016

Blood compatible heparin–benzalkonium modified montmorillonite /PDMS composites

Co-reporter:Na-Meng, Ning-Lin Zhou

Applied Clay Science (December 2012) Volume 70() pp:22-27

Publication Date(Web):December 2012

DOI:10.1016/j.clay.2012.08.012

Montmorillonite–phosphatidyl choline/PDMS films: A novel antithrombogenic material

Co-reporter:Ninglin Zhou, Su Fang, Dong Xu, Jun Zhang, Hong Mo, Jian Shen

Applied Clay Science (December 2009) Volume 46(Issue 4) pp:401-403

Publication Date(Web):December 2009

DOI:10.1016/j.clay.2009.10.012

Controlled release and antibacterial activity chlorhexidine acetate (CA) intercalated in montmorillonite

Co-reporter:Na Meng, Ning-Lin Zhou, Shuang-Quan Zhang, Jian Shen

International Journal of Pharmaceutics (1 December 2009) Volume 382(Issues 1–2) pp:45-49

Publication Date(Web):1 December 2009

DOI:10.1016/j.ijpharm.2009.08.004

The aim of this study was to prepare chlorhexidine acetate (CA)/montmorillonite intercalation composites and its antibacterial potential was evaluated with pathogenic bacteria, Staphylococcus aureus and Pseudomonas aeruginosa. The CA/MMT was characterized by X-ray diffraction (XRD), Fourier transformed infrared (FT-IR), and thermogravimetric analysis (TGA). CA was successfully intercalated into the interlayer of MMT and in vitro release properties of the intercalated CA have been investigated in phosphate buffered saline media (pH 7.4) at 37 ± 0.5 °C. At drug release study, CA showed initial burst effect for 24 h and then continuously released for 72 h. Their antibacterial activity was assayed by the inhibitory zone method. The CA/MMT was tested for antimicrobial activity against S. aureus and P. aeruginosa. The CA/MMT strongly inhibited the growth of a wide variety of microorganisms, including Gram-positive bacteria, Gram-negative bacteria.