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Mallick, Sudipta,Thuy, Le Thi,Lee, Seulgi,Park, Jong-II,Choi, Joon Sig Elsevier 2018 Colloids and surfaces. B, Biointerfaces Vol.161 No.-
<P><B>Abstract</B></P> <P> <UL> <LI> Mitochondria are exclusively employed to produce energy required for the vital metabolic functions of the cell. However, mitochondria also play a key role in mammalian cell death. Dissipation in the mitochondria membrane potential causes cell death. Therefore, in cancer therapy, mitochondria are a novel target. Herein, we developed a nano-formulation of Antimycin A specifically targeted towards mitochondria and lung cancer; A549 cell. The liposomes were prepared using cholesterol and a mitochondria-penetrating peptide (MPP) having a phenylalanine-arginine-phenylalanine-lysine (FRFK) peptide sequence. The FRFK peptide was synthesized using solid phase peptide synthesis (SPPS) and contained cholesterol in the N-terminal end of the phenylalanine (Chol-FRFK). The synthesized material was confirmed using <SUP>1</SUP>H NMR, Fourier transform infrared spectroscopy (FT-IR) and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI TOF/MS). 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and Chol-FRFK, at a molar ratio of 1:1, were used for liposomal (Chol-FRFK/D) formulations; the sizes of the liposomes were confirmed using dynamic light scattering (DLS). Cytotoxicity was evaluated in A549 cells. Cellular uptake and mitochondria targeting were confirmed by flow cytometry and confocal microscopy, respectively. Antimycin A, a hydrophobic and mitochondrial electron transporter inhibitor was encapsulated into the Chol-FRFK/D liposomes. Our results indicate that Chol-FRFK/D liposomes may potentially be used for the nano-formulation of cytotoxic drugs and enhancing their bioavailability in cancer therapy. </LI> </UL> </P> <P><B>Highlights</B></P> <P> <UL> <LI> Idea of mitochondria targeting carrier to deliver mitochondria-specific drug, is proposed. </LI> <LI> Chol-FRFK was synthesized as a liposomal component. </LI> <LI> Chol-FRFK/D liposomes were prepared for delivery of Antimycin A to the mitochondria. </LI> <LI> Nano-formulation of Antimycin A showed higher toxicity in A549 cells. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Silica coated gold nanorods for imaging and photo-thermal therapy of cancer cells.
Mallick, Sudipta,Sun, In-Cheol,Kim, Kwangmeyung,Yil, Dong Kee American Scientific Publishers 2013 Journal of Nanoscience and Nanotechnology Vol.13 No.5
<P>Due to their efficient conversion of absorbed light energy to heat gold nanorods have been proved to be an amazing tool for minimally invasive photo-thermal cancer therapy. The present in vitro study demonstrates the ability of silica coated Au nanorods to function as a dual probe for cancer-cell therapy and imaging without any toxic side-effects. HeLa cells were incubated with silica coated Au nanorods and imaged inside the cell just after 1 hour of incubation by a dark field set up due to strong surface enhanced Raman scattering. To induce hyperthermia, silica coated Au nanorod incubated HeLa cells were illuminated with a diode laser (671 nm, 200 mW, 10 min). Cell destruction was observed even at a very low dose of nanorods, whereas none was observed in the absence of nanorods. Silica coated Au nanorods thus offer a promising, novel class of selective photo-thermal agents for cancer therapy and diagnosis.</P>
Hyaluronic Acid–Ceramide-based Liposomes for Targeted Gene Delivery to CD44-Positive Cancer Cells
Sudipta Mallick,박정현,조현종,김대덕,최준식 대한화학회 2015 Bulletin of the Korean Chemical Society Vol.36 No.3
Hyaluronic acid–ceramide (HACE)-modified liposomes were designed using 1,2-dioleoyl-sn-glycero-3-phoshphoethanolamine (DOPE) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) for targeted delivery of therapeutic genes to the CD44 receptor-overexpressing cancer cells. Liposomes were prepared with different molar ratios of HACE; the most efficient formulation was tested for further in vitro experiments. The size and zeta potential of HACE-based liposomes were characterized by a Zetasizer. Lipoplex was then prepared at different nitrogen/phosphate (N/P) ratios; the gel retardation test showed strong DNA-binding affinity of liposomes for targeted gene delivery. Cytotoxicity of liposomes was evaluated by colorimetric assay (WST assay) for different cell lines such as MDA-MB-231 and NIH3T3 cells. HACE liposomes showed negligible cytotoxicity both in MDA-MB-231 and NIH3T3 cells that endow them for further therapeutic studies. We then examined the transfection efficiency of liposomes using luciferase reporter plasmid DNA. We found transfection efficiency of HACE-based liposomes was remarkably higher in case of MDA-MB-231 cells as compared to NIH3T3 cells. This result was indicative for higher receptor-binding endocytosis uptake of HACE liposomes and subsequent transfection in CD44 receptor-positive cell lines. Our findings have shown interesting prospective for tumor-targeted delivery of therapeutic gene in CD44 receptor-positive cells with less cytotoxic effects.
양봉석,Sudipta Mallick,권용은,김윤중,김근희,최준식 대한화학회 2015 Bulletin of the Korean Chemical Society Vol.36 No.10
Cell-penetrating peptides (CPPs), originated from membrane translocating sequences of viruses, can deliver biomolecules effectively into cells. Research on natural and synthetic CPPs, for delivering drugs and genes reveals that this process requires cellular uptake independent of receptors and endosomes to minimize damage to the cell membrane. To this end, we conjugated CPP-derived oligopeptides to the surface of polyamidoamine (PAMAM) dendrimers to develop novel nanocarriers that improve cellular uptake transfection efficiency. PAMAM generation 4 (G4) was conjugated with oligopeptides composed of lysine and phenylalanine (KFF, FFK). The DNA condensation efficiency of PAMAM G4-KFF and PAMAM G4-FFK was determined using an agarose gel retardation assay. The sizes of the polyplexes were determined using dynamic light scattering as well as scanning and transmission electron microscopy. Cytotoxicity and transfection efficiency were evaluated using the HeLa and HepG2 cells. The transfection efficiencies of PAMAM G4-KFF and PAMAM G4-FFK were comparable with that of the gold-standard transfection reagent polyethylenimine (PEI25 kDa). These results suggest that these nanocarriers will serve as efficient non-viral vehicles for gene therapy.
레티쑤이,Sudipta Mallick,김성연,최준식 한국화학공학회 2023 Korean Journal of Chemical Engineering Vol.40 No.2
In this study, a new kind of antibiotic drug-polymer conjugate, the kanamycin-methyl acrylate-polyethylenimine (KMP) polymer, was synthesized and characterized as gene carrier. Previous reports have shown that the modification of low molecular weight polyethylenimine (LMW-PEI) improves the transfection efficiency and decreases the toxicity. Kanamycin can be hydrolyzed under an acidic environment owing to the glycosidic bond. In this physicochemical study, the properties of the kanamycin-based hybrid polymers conjugated with various LMW-PEIs, such as 0.6, 1.2, and 2kDa polyethylenimine (PEI), were investigated by 1H NMR, FT-IR, and their buffering capacity was assayed by acid-base titration method. Gel electrophoresis and picogreen assay were performed to evaluate the ability to bind with plasmid DNA. The polyplexes were nanosized with a net positive charge. The cytotoxicity and transfection efficiency were evaluated using human cervical carcinoma (HeLa) cells. KMPs exhibited lower toxicity than PEI 25 kDa, and higher transfection efficiency compared to the native LMW-PEIs.
배윤희,정민교,문지영,Sudipta Mallick,송수정,김동민,고경수,한진,최준식 대한화학회 2018 Bulletin of the Korean Chemical Society Vol.39 No.1
Mesenchymal stem cells (MSCs) can self-renew and differentiate into multiple cell types. The delivery of drugs to MSCs is an important tool in the emerging fields of tissue regeneration and engineering. In this study, we determined the anticancer efficiency of DQAsomes, which displayed affinity toward human adipose-derived mesenchymal stem cells (AD-MSCs). Cytotoxicity assays were conducted to examine human AD-MSCs. We also evaluated the cellular effects of human AD-MSCs treated with DQAsomes by cell cycle distribution analysis, annexin-V propidium iodide staining, and H2DCFDA and found that DQAsomes promoted the differentiation of AD-MSCs into osteoblast cells. Furthermore, flow cytometry analysis revealed that human AD-MSCs treated with DQAsomes maintained the phenotypic characteristics of human AD-MSCs. We demonstrated that DQAsomes can be used in tissue engineering and have clinical relevance as effective drug and protein delivery systems.
Synthesis and characterization of bioreducible cationic biarm polymer for efficient gene delivery
Kim, Yugyeong,Uthaman, Saji,Nurunnabi, Md,Mallick, Sudipta,Oh, Keun Sang,Kang, Sun-Woong,Cho, Sungpil,Kang, Han Chang,Lee, Yong-kyu,Huh, Kang Moo Elsevier 2018 International journal of biological macromolecules Vol.110 No.-
<P><B>Abstract</B></P> <P>We synthesized a new cationic AB<SUB>2</SUB> miktoarm block copolymer consisting of one poly (ethylene glycol) (PEG) block and two cationic poly (<SMALL>L</SMALL>-lysine) (PLL) blocks, wherein the PLL blocks were conjugated to the PEG blocks with or without a bioreducible linker (disulfide bonds). Bioreducible and non-bioreducible miktoarm block copolymers (mPEG-(ss-PLL)<SUB>2</SUB> and mPEG-PLL<SUB>2</SUB>) were prepared for efficient gene delivery as a non-viral gene delivery approach. Both cationic copolymers (bioreducible and nonbioreducible) efficiently formed the nanopolyplexes with plasmid DNA (pDNA) through electrostatic interaction at different weight ratio of polymer and pDNA. Gene condensation ability of the polymers and release of the DNA under reduction condition were measured by gel electrophoresis. Dynamic light scattering (DLS) and field-emission transmission electron microscopy (FE-TEM) were used to measure the average hydrodynamic diameter and morphology of the nanoparticles, respectively. The bioreducible nanopolyplexes showed lower cytotoxicity and higher gene expression than the non-reducible nanopolyplexes in cancer cells.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>