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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>
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>
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>
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.