Prussian blue decorated mesoporous silica hybrid nanocarriers for photoacoustic imaging-guided synergistic chemo-photothermal combination therapy

Santha Moorthy, Madhappan,Hoang, Giang,Subramanian, Bharathiraja,Bui, Nhat Quang,Panchanathan, Manivasagan,Mondal, Sudip,Thi Tuong, Vy Phan,Kim, Hyehyun,Oh, Junghwan The Royal Society of Chemistry 2018 Journal of materials chemistry. B, Materials for b Vol.6 No.32

<P>The fabrication of nanotherapeutic systems capable of stimuli-responsive drug delivery and photoacoustic imaging (PAI)-guided photothermal therapy (PTT) is considered significant for chemo-photothermal therapy applications in cancer therapy. In the present study, the Prussian blue nanoflake (PBNF) decorated mesoporous silica hybrid nanoparticle (PB@MSH-EDA NPs) is reported for PAI-guided chemo-photothermal therapy applications. The amine group enriched mesoporous silica channels can be used to encapsulate an anticancer drug for chemotherapy, and the surface decorated PBNFs can convert a near-infrared (NIR) laser (808 nm) into heat for photothermal therapy and can also be used for PAI applications. The PB@MSH-EDA NPs show pH-responsive drug release efficiency under acidic pH (pH 5.0 and 4.0) conditions. Furthermore, the PB@MSH-EDA NPs system shows strong NIR laser absorption and photothermal conversion efficiency under 808 nm laser irradiation. The <I>in vitro</I> experimental result shows that the PB@MSH-EDA NPs are biocompatible and could be efficiently taken up by MDA-MB-231 cells. In addition, the <I>in vivo</I> results demonstrate that the tumor-bearing mice fully recovered after injecting the drug (Dox)-loaded PB@MSH-EDA/Dox NPs and being further irradiated with the 808 nm laser. We believe that the PB@MSH-EDA NPs system could be utilized as an efficient PAI-guided chemo-photothermal therapy agent for the detection and treatment of tumors in an emerging cancer therapy application.</P>

Multifunctional Periodic Mesoporous Organosilicas for Biomolecule Recognition, Biomedical Applications in Cancer Therapy, and Metal Adsorption

Moorthy, Madhappan Santha,Kim, Mi‐,Ju,Bae, Jae‐,Ho,Park, Sung Soo,Saravanan, Nagappan,Kim, Sun‐,Hee,Ha, Chang‐,Sik WILEY‐VCH Verlag 2013 European journal of inorganic chemistry Vol.2013 No.17

<P><B>Abstract</B></P><P>This paper reports a new approach towards the construction of a multifunctional periodic mesoporous organosilica (PMO), which integrates a range of advantages, such as mesoporous structural order, selective nucleobase‐recognition properties, stimuli‐responsive site‐specific delivery of anticancer agents to cancer tissues, and Cu<SUP>2+</SUP> adsorption, into a single entity. First, the appropriate organic‐functional‐receptor precursor was synthesized by a chemical process and used to fabricate a multifunctional pyridine‐containing PMO material (DMPy‐PMO) by a hydrolysis and condensation route. The designed organic–inorganic hybrid mesoporous silica chemosensor showed an intrinsic selective recognition of nucleobase, specifically thymidine, through multipoint hydrogen‐bonding interactions with suitably arrayed receptor sites loaded into the rigid silica framework. An in vitro cytotoxicity test showed that the designed chemosensor materials have good biocompatibility and, therefore, could be promising candidates for the delivery of a range of therapeutic agents. Confocal laser scanning microscopy (CLSM) confirmed that the material can be internalized effectively by cancer cells (MCF‐7 cells). In addition, the DMPy‐PMOs showed efficient Cu<SUP>2+</SUP> ion removal capacity at pH 5.0 with significantly high levels of adsorption (0.95 mmol g<SUP>–1</SUP>). These results suggest that the prepared multifunctional PMO hybrid has potential use as a smart material for a range of applications, such as biomolecule recognition, biomedical applications, and as an efficient adsorbent for the removal of metal ions.</P>

Step-up synthesis of amidoxime-functionalised periodic mesoporous organosilicas with an amphoteric ligand in the framework for drug delivery

Santha Moorthy, Madhappan,Park, Sung-Soo,Fuping, Dong,Hong, Sang-Hyun,Selvaraj, M.,Ha, Chang-Sik The Royal Society of Chemistry 2012 Journal of materials chemistry Vol.22 No.18

<P>The step-up synthesis of amidoxime-functionalised periodic mesoporous organosilicas (PMOs) with an ordered hexagonal structure was achieved in two steps: (i) direct co-condensation of diaminomaleonitrile and 3-isocyanatopropyltriethoxysilane (IPTES) and (ii) chemical modification of bridged nitrile into amidoxime using a hydroxylamine hydrochloride (NH<SUB>2</SUB>OH·HCl) reagent. The synthesis approach allowed a high loading of amidoxime functional groups in the pore wall framework of the mesoporous materials with controlled regular morphologies. The resulting materials with various diureylenemaleonitrile contents (up to 40 mol%) contained ordered hexagonal mesopores. The highly ordered hexagonal arrangement of the pores with a high degree of uniformity of amidoxime-functionalised PMOs was confirmed by low-angle X-ray diffraction (XRD), N<SUB>2</SUB> adsorption isotherms, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The composition of the mesoporous organosilica was further characterised by Fourier transform infrared (FT-IR) spectroscopy, <SUP>29</SUP>Si magic angle spinning (MAS) and <SUP>13</SUP>C cross-polarization (CP) MAS nuclear magnetic resonance (NMR) spectroscopy. The synthesised materials with an amphoteric ligand in the framework were found to be suitable carrier materials for controlled drug delivery systems in a phosphate buffer solution at pH 6.0, 7.4 and 9.0 for both hydrophobic (ibuprofen) and hydrophilic drugs (5-fluorouracil).</P> <P>Graphic Abstract</P><P>This paper reports new periodic mesoporous organosilicas (PMOs) with double active functional groups, <I>i.e.</I> ureylene and amidoxime groups, <I>via</I> a step-up synthesis using diaminomaleonitrile and 3-isocyanatopropyltriethoxysilane, which are suitable for controlled drug delivery systems in both hydrophobic (ibuprofen) and hydrophilic drugs (5-fluorouracil). <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c2jm16341a'> </P>

Mesoporous organosilica hybrids with a tunable amphoteric framework for controlled drug delivery

Moorthy, Madhappan Santha,Park, Ji-Hye,Bae, Jae-Ho,Kim, Sun-Hee,Ha, Chang-Sik The Royal Society of Chemistry 2014 Journal of Materials Chemistry B Vol.2 No.38

<P>The chemical conversion of nitrile groups integrated in the pore wall frameworks of mesoporous organosilica hybrids (MSHs) into either carboxylic acid groups or amine groups by an acid or base hydrolysis method without altering the mesostructural order is suggested. By this approach, bifunctional derivatives could be produced in the silica pore walls. The nitrile groups integrated covalently into the pore walls of the mesoporous organosilica hybrids were converted to reactive functionalities, such as carboxylic acid (-COOH) or amine (-NH2) groups, by treatment with H2SO4or LiAlH4as the catalytic reagents. This facile approach allows the production of high amounts of either -COOH groups (3.26 mmol g<SUP>−1</SUP>) or amine (-NH2) groups (4.13 mmol g<SUP>−1</SUP>) into the pore walls of the mesoporous organosilica hybrids. The synthesised materials were characterised by X-ray diffraction, N2sorption isotherms, Fourier transform infrared spectroscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and solid state<SUP>13</SUP>C cross-polarization magic angle spinning nuclear magnetic resonance spectroscopy (CP MAS NMR). Owing to the presence of hydrophilic basic diurea functional groups and -COOH or -NH2derivatives in the pore walls, the obtained samples could behave like bifunctional materials. The mesoporous organosilica hybrids with chemically derivatised carboxylic acid groups or amine functionalities in the pore wall frameworks were found to be suitable drug carriers for the controlled delivery of both hydrophilic (for example, 5-FU) and hydrophobic (<I>e.g.</I>IBU) drugs under an intracellular environment. The biocompatibility of the synthesised materials was also evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cellular uptake was monitored by confocal laser scanning microscopy (CLSM). These results show that the synthesised materials have potential use as efficient carriers for drug delivery applications.</P>

Chitosan oligosaccharide coated mesoporous silica nanoparticles for pH-stimuli responsive drug delivery applications

Moorthy, Madhappan Santha,Hoang, Giang,Manivasagan, Panchanathan,Mondal, Sudip,Vy Phan, Thi Tuong,Kim, Hyehyun,Oh, Junghwan Springer-Verlag 2019 Journal of porous materials Vol.26 No.1

A modified mesoporous silica optical nanosensor for selective monitoring of multiple analytes in water

Moorthy, Madhappan Santha,Cho, Hun-Jeong,Yu, Eun-Jeong,Jung, Young-Sik,Ha, Chang-Sik The Royal Society of Chemistry 2013 Chemical communications Vol.49 No.78

<P>A new modified mesoporous silica nanosensor was synthesized by the co-condensation method. Under basic conditions, the obtained mesoporous silica nanosensor responds selectively to Fe<SUP>2+</SUP> (pH = 8) and Cu<SUP>2+</SUP> (pH = 12) with a distinguishable colour change perceivable by the naked eye and a detection limit of approximately 50 ppb.</P> <P>Graphic Abstract</P><P>A modified mesoporous silica nanosensor has been synthesized for colorimetric selective detection of both Fe<SUP>2+</SUP> and Cu<SUP>2+</SUP> simultaneously using a single entity with an obvious color change under basic conditions (pH = 8 or 12, respectively). <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c3cc42513d'> </P>

Periodic mesoporous organosilica (PMO) for catalytic applications

박성수,하창식,Madhappan Santha Moorthy 한국화학공학회 2014 Korean Journal of Chemical Engineering Vol.31 No.10

Surfactant-templated binuclear alkoxysilane precursors or cyclic silsesquioxane precursors have led to anew class of nanocomposites with bridging organic groups (R) inside the channel walls, known as periodic mesoporousorganosilica (PMO). These PMO materials facilitate chemistry of the channels and provide new opportunities for con-trolling the chemical, physical, mechanical, and dielectric properties of the materials. This review provides an overviewof recent papers on the synthesis of PMOs and their applications as catalysts published after the year 2000.

Periodic mesoporous organosilicas for advanced applications

Park, Sung Soo,Santha Moorthy, Madhappan,Ha, Chang-Sik Nature Publishing Group 2014 NPG Asia Materials Vol.6 No.-

Photo-based PDT/PTT dual model killing and imaging of cancer cells using phycocyanin-polypyrrole nanoparticles

Bharathiraja, Subramaniyan,Manivasagan, Panchanathan,Santha Moorthy, Madhappan,Bui, Nhat Quang,Jang, Bian,Phan, Thi Tuong Vy,Jung, Won-Kyo,Kim, Young-Mok,Lee, Kang Dae,Oh, Junghwan Elsevier 2018 EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEU Vol.123 No.-

<P><B>Abstract</B></P> <P>Photodynamic therapy (PDT) and photothermal therapy (PTT) using nanoparticles have gained significant attention for its therapeutic effect for cancer treatment. In the present study, we fabricated polypyrrole nanoparticles by employing bovine serum albumin-phycocyanin complex and the formulated particles were stable in various physiological solutions like water, phosphate buffered saline and culture media. The formulated nanoparticles did not cause any noticeable toxicity to MDA-MB-231 and HEK-293 cells. The obtained nanoparticles effectively killed MDA-MB-231 cells in a dual way upon laser illumination, one is through phycocyanin propagated reactive oxygen species (PDT) upon laser illumination and in another way it eradicated the treated cells by converting optical energy into heat energy (PTT). Additionally, the nanoparticles generated good amplitude of ultrasound signals under photoacoustic imaging (PAT) system that facilitates imaging of treated cells. In conclusion, the fabricated particles could be used as a multimodal therapeutic agent for treatment of cancer in the biomedical field.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Phycocyanin-BSA stabilized polypyrrole nanoparticles (Ppy@BSA-Pc) formulated. </LI> <LI> Ppy@BSA-Pc can be applied to PDT and PTT treatment. </LI> <LI> Ppy@BSA-Pc facilitates imaging of treated cells under PAI system. </LI> <LI> Ppy@BSA-Pc can act as a theranostic agent in biomedical field. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Anti-EGFR Antibody Conjugation of Fucoidan-Coated Gold Nanorods as Novel Photothermal Ablation Agents for Cancer Therapy

Manivasagan, Panchanathan,Bharathiraja, Subramaniyan,Santha Moorthy, Madhappan,Oh, Yun-Ok,Song, Kyeongeun,Seo, Hansu,Oh, Junghwan American Chemical Society 2017 ACS APPLIED MATERIALS & INTERFACES Vol.9 No.17

<P>The development of novel photothermal ablation agents as cancer nanotheranostics has received a great deal of attention in-recent decades. Biocompatible fucoidan (Fu) is used as the coating material for gold nanorods (AuNRs) and subsequently conjugated with monoclonal antibodies against epidermal growth factor receptor (anti-EGFR) novel photothermal ablation agents for,cancer nanotheranostics because of their excellent biocompatibility, biodegradability, nontoxicity, water solubility, photostability, ease of Surface modification, strongly enhanced absorption in near-infrared (NIR) regions, target specificity, minimal invasiveness, fast recovery, and prevention. of damage to normal tissues: Anti-EGFRFu-AuNRs have an average particle size of 96.37 +/- 3.73 nm. Under 808 nm NIR laser at 2 W/cm(2) for 5 min, the ternperathre of the solution containing anti-EGFR Fu-AuNRs,(30 mu g/mL) increased by 52.1 degrees C. The anti-EGFR Fu-AuNRs exhibited high efficiency for the ablation of MDA-MB-231 cells in vitro. In viva- photothermal ablation exhibited that tumor tissues fully recovered without recurrence and finally were reconstructed with normal-tissues by-the 808 nm NIER. laser irradiatiOn after injection of anti-EGFR Fu-AuNRs. These results suggest that the anti-BUR Fu-AuNRs would be novel photoablation agents for future cancer nanotheranostics:</P>