Imaging of Gastrointestinal tract by Absorption of QD s Heparin DOCA nanoparticles

Zehedina Khatun Md Nurunnabi,조서현,이용규 한국고분자학회 2010 한국고분자학회 학술대회 연구논문 초록집 Vol.2010 No.4

Bioreducible Poly(ethylene glycol)–Triphenylphosphonium Conjugate as a Bioactivable Mitochondria-Targeting Nanocarrier

Khatun, Zehedina,Choi, Yeon Su,Kim, Yu Gyeong,Yoon, Kwonhyeok,Nurunnabi, Md,Li, Li,Lee, Eunji,Kang, Han Chang,Huh, Kang Moo AMERICAN CHEMICAL SOCIETY 2017 Biomacromolecules Vol. No.

<P>Bioactivable nanocarrier systems have favorable characteristics such as high cellular uptake, target specificity, and an efficient intracellular release mechanism. In this study, we developed a bioreducible methoxy polyethylene glycol (mPEG) triphenylphosphonium (TPP) conjugate (i.e., mPEG (ss-TPP)(2) conjugate) as a vehicle for mitochondrial drug delivery. A bioreducible linkage with two disulfide bond containing end groups was used at one end of the hydrophilic mPEG for conjugation with lipophilic TPP molecules. The amphiphilic mPEG (ss-TPP)(2) self-assembled in aqueous media, which thereby formed core shell structured nano particles (NPs) with good colloidal stability, and efficiently encapsulated the lipophilic anticancer drug doxorubicin (DOX). The DOX-loaded mPEG (ss-TPP)(2) NPs were characterized in terms of their physicochemical and morphological properties, drug-loading and release behaviors, in vitro anticancer effects, and mitochondria-targeting capacity. Our results suggest that bioreducible DOX-loaded mPEG (ss-TPP)(2) NPs can induce fast drug release with enhanced mitochondrial uptake and have a better therapeutic effect than nonbioreducible NPs.</P>

Oral Delivery of Near-Infrared Quantum Dot Loaded Micelles for Noninvasive Biomedical Imaging

Khatun, Zehedina,Nurunnabi, Md,Cho, Kwang Jae,Lee, Yong-kyu American Chemical Society 2012 ACS APPLIED MATERIALS & INTERFACES Vol.4 No.8

<P>The purpose of this study is to design, develop, and characterize an optical imaging agent for oral administration. The hydrophobic, nanosized (7 nm), near-infrared (NIR) quantum dots (QDs) have been loaded into deoxycholic acid (DOCA) conjugated low molecular weight heparin (LMWH) micelles. The QD-loaded LMWH-DOCA (Q-LHD) nanoparticles have been characterized by electrophoretic light scattering (ELS) and a transmission electron microscope (TEM) which shows the average particle size was 130–220 nm in diameter. The Q-LHD nanoparticles also show the excellent stability in different pH conditions, and the release profile demonstrates the slow release of QDs after 5 days of oral administration. Concfocal laser microscopic scanning images show that the Q-LHD nanoparticles penetrate the cell membrane and are located inside the cell membrane. The real time pharmacokinetics studies show the absorption, distribution, metabolism, and elimination profile of Q-LHD nanoparticles, observed by the Kodak molecular imaging system (KMIS). This study has demonstrated that the orally administered Q-LHD nanoparticles are absorbed in the small intestine through the bile acid transporter and eliminated through the kidneys.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/aamick/2012/aamick.2012.4.issue-8/am301048m/production/images/medium/am-2012-01048m_0010.gif'></P>

Near infra-red photoluminescent graphene nanoparticles greatly expand their use in noninvasive biomedical imaging

Nurunnabi, Md,Khatun, Zehedina,Reeck, Gerald R.,Lee, Dong Yun,Lee, Yong-kyu The Royal Society of Chemistry 2013 Chemical communications Vol.49 No.44

<P>A simple reaction process is developed to synthesize blue, green, yellow and red colour graphene nanoparticles (GNPs) from carbon fibers. Here, we have focused on synthesis of near infra-red GNPs and their biological application for optical imaging of deep tissues and organs.</P> <P>Graphic Abstract</P><P>The near infra-red (NIR) graphene nanoparticles (GNPs) have been synthesized from carbon fiber by controlling the reaction parameters. The NIR GNPs have been injected into nude mice through tail vain and tested for noninvasive optical imaging. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c3cc42334d'> </P>

A hyaluronic acid nanogel for photo-chemo theranostics of lung cancer with simultaneous light-responsive controlled release of doxorubicin.

Khatun, Zehedina,Nurunnabi, Md,Nafiujjaman, Md,Reeck, Gerald R,Khan, Haseeb A,Cho, Kwang Jae,Lee, Yong-kyu RSC Pub 2015 Nanoscale Vol.7 No.24

<P>The combined delivery of photo-and chemo-therapeutic agents is an emerging strategy to overcome drug resistance in treating cancer, and controlled light-responsive drug release is a proven tactic to produce a continuous therapeutic effect for a prolonged duration. Here, a combination of light-responsive graphene, chemo-agent doxorubicin and pH-sensitive disulfide-bond linked hyaluronic acid form a nanogel (called a graphene-doxorubicin conjugate in a hyaluronic acid nanogel) that exerts an activity with multiple effects: thermo and chemotherapeutic, real-time noninvasive imaging, and light-glutathione-responsive controlled drug release. The nanogel is mono-dispersed with an average diameter of 120 nm as observed by using TEM and a hydrodynamic size analyzer. It has excellent photo-luminescence properties and good stability in buffer and serum solutions. Graphene itself, being photoluminescent, can be considered an optical imaging contrast agent as well as a heat source when excited by laser irradiation. Thus the nanogel shows simultaneous thermo-chemotherapeutic effects on noninvasive optical imaging. We have also found that irradiation enhances the release of doxorubicin in a controlled manner. This release synergizes therapeutic activity of the nanogel in killing tumor cells. Our findings demonstrate that the graphene-doxorubicin conjugate in the hyaluronic acid nanogel is very effective in killing the human lung cancer cell line (A549) with limited toxicity in the non-cancerous cell line (MDCK).</P>

Photoluminescent Graphene Nanoparticles for Cancer Phototherapy and Imaging

Nurunnabi, Md,Khatun, Zehedina,Reeck, Gerald R.,Lee, Dong Yun,Lee, Yong-kyu American Chemical Society 2014 ACS APPLIED MATERIALS & INTERFACES Vol.6 No.15

<P>Graphene-based nanomaterials are of great interest in a wide range of applications in electronics, the environment, and energy as well as in biomedical and bioengineering. Their unique properties make them generally applicable as prognostic, diagnostic, and therapeutic agents in cancer. In this work, we focused on photodynamic and photothermal therapeutic properties of our previously synthesized carboxylated photoluminescent graphene nanodots (cGdots). The cGdots are ∼5 nm in diameter and excited at 655 nm. Our findings reveal that, upon laser irradiation by near-infrared (wavelength 670 nm) sensitizer, electrons of the cGdots starts to vibrate and form electron clouds, thereby generating sufficient heat (>50 °C) to kill the cancer cells by thermal ablation. The generation of singlet oxygen also occurs due to irradiation, thus acting similarly to pheophorbide-A, a well-known photodynamic therapeutic agent. The cGdots kills MDA-MB231 cancer cells (more than 70%) through both photodynamic and photothermal effects. The cGdots were equally effective in the <I>in vivo</I> model of MDA-MB231 xenografted tumor-bearing mice also as observed for 21 days. The cGdot was intravenously injected, and the tumor was irradiated by laser, resulting in final volume of tumor was ∼70% smaller than that of saline-treated tumor. It indicates that the growth rate of cGdot-treated tumor was slower compared to saline-treated tumor. The synthesized cGdots could enable visualization of tumor tissue in mice, thereby illustrating their use as optical imaging agents for detecting cancer noninvasively in deep tissue/organ. Collectively, our findings reveal that multimodal cGdots can be used for phototherapy, through photothermal or photodynamic effects, and for noninvasive optical imaging of deep tissues and tumors simultaneously.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/aamick/2014/aamick.2014.6.issue-15/am504071z/production/images/medium/am-2014-04071z_0006.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/am504071z'>ACS Electronic Supporting Info</A></P>

Optical Imaging, Biodistribution and Toxicity of Orally Administered Quantum Dots Loaded Heparin-Deoxycholic Acid

Zehedina Khatun,이용규,Md. Nurunnabi,이동윤,김연정,변영로,조광재 한국고분자학회 2015 Macromolecular Research Vol.23 No.7

Quantum dots (QDs) are considered to be one of the most promising optical imaging probes for biological and biomedical applications. However toxicology is the major concern that limits biological application. Though couple of studies have reported focusing on intravenous administration but, in this study, we have observed toxicity of orally administered QDs for the very first time. QDs were loaded into heparin-conjugated deoxycholic acid (QLHD) conjugates. The orally administered Q-LHD nanoparticles were absorbed through bile acid transporter of small intestine. In vitro genotoxicity was observed by chromosomal aberration and comet assay to learn effect of quantum dot in cell mutation. The amount of cadmium content in different organs was also measured by inductive coupled plasma mass spectroscopy. To observe physiological changes, complete blood count, serum biochemistry and organ histology of Q-LHD treated rats were performed accordingly. The in vivo biodistribution results confirm any acute toxicity or significant variations were noted in the rats. Furthermore, oral administration of the Q-LHD nanoparticles does not cause appreciable toxicity, showing no mentionable histological changes of the organs at 45 days after single dose. Though this current study reveals, potential toxicity of Q-LHD nanoparticles is no longer a limiting factor for extending application of QDs in biomedical imaging but long term in vivo genotoxicity studies further required.