个人简介
Pursuing cutting-edge research in the areas of pharmaceutical nanomedicine / nanobiotechnology / chemical biology / medicinal chemistry / targeted drug delivery / cancer therapy / infectious diseases detection / translational medicine / systems biology / toxicology / synthetic biopolymer chemistry / hyperbranched polymers and dendrimers / organic synthesis.
2013 - Present Assistant Professor. Department of Chemistry and KPRC, Pittsburg State University, Pittsburg, Kansas, U.S.A.
2010 - 2012 Research Assistant Professor. Nanoscience Technology Center, University of Central Florida, Orlando, Florida, U.S.A.
2007 - 2009 Postdoctoral Research Associate. Nanoscience Technology Center, University of Central Florida, Orlando, Florida, U.S.A.
Ph.D., Synthetic polymer chemistry and organic chemistry, Indian Institute of Technology-Bombay (IIT-Bombay), Mumbai, India, 2006
M.Sc., Organic Chemistry, Banaras Hindu University (BHU), Varanasi, India, 2000
B.Sc., Chemistry, Ramakrishna Mission College-Narendrapur. University of Calcutta, India, 1998
研究领域
PROJECT 1: Polymeric nanotheranostics for the targeted imaging and treatment of cancers.
A. FACILE, ONE-STEP, SELECTIVE N-ALKYLATION OF AMINO ACIDS: Novel polymeric drug delivery system for the treatment of cancer. Published in Biomacromolecules 2011, 12, 3917.
Novel one-step methodology for selective mono and di- N-alkylation of various amino acids, without using conventional multi-step protection and deprotection methods. The newly developed one-step synthetic strategy was used for the one-step synthesis of amino acid-based small molecules, biopolymers and theranostic polymeric nanoagents. The fabricated theranostic nano-vehicle was efficient in encapsulating and delivering therapeutic drugs and dyes to the tumors. The results successfully proven the ability to target and killing of lung (A549 cells) and prostate cancers (LNCaP and PC-3 cells).
In vivo experiments showed the accumulation of glutamated- and folate-decorated DiR dye encapsulating polymeric nanoparticles in PSMA positive PC-3 tumor in mice. Increased uptake is observed for all time points in the PSMA-positive PC3-PSMA tumor.
B. Step-wise organic synthesis of biocompatible hyperbranched polymers and therapeutic drug encapsulating nanoparticles and nanocomposites for the treatment of CANCER. Published in Molecular Pharmaceutics 2012, 9, 2080, Langmuir 2010, 26, 5364, Chemical Communications 2004, 2126.
Novel functional hyperbranched polymers were synthesized using simple organic chemistry and utilized for the synthesis of a biocompatible HBPE polymer. The polymer’s globular structure with functional surface carboxylic groups and hydrophobic cavities residing in the polymer’s interior allows for the formation of multifunctional polymeric nanoparticles, which are able to encapsulate a diversity of hydrophobic cargos. Solvent diffusion method and click chemistry has been followed for the synthesis of targetable functional nanoparticles and nanocomposites. These polymeric nanocomposites showed excellent magnetic, fluorescent, MRI imaging, x-ray contrast and catalytic activity when conjugated with dye encapsulating HBPE nanoparticles, iron oxide and cerium oxide nanoparticles. This offers the possibility to create novel multifunctional materials composed of hyperbranched polymeric nanoparticles with unique properties that can be tailored by the nature of their cargo, their surface functionality and the formation of supramolecular assemblies. Specifically, we examined the cytotoxic properties of a novel peptide, CT20p, derived from the C-terminal, alpha-9 helix of Bax, an amphipathic domain with putative membrane binding properties. The amphipathic nature of CT20p allowed it to be encapsulated in polymeric nanoparticles (NPs) that have the capacity to harbor targeting molecules, dyes or drugs. The resulting CT20p-NPs proved an effective killer, in vitro, of colon and breast cancer cells, and in vivo, using a murine breast cancer tumor model.
C. Novel Bifunctional System for targeted delivery of therapeutic membrane-impermeable proteins and peptides to tumors and imaging of cancer therapy. Published in Molecular Pharmaceutics 2011, 7, 1209.
A water-soluble hydrophilic hyperbranched polymer has been designed for the encapsulation of water-soluble drugs doxorubicin, cytochrome C and other proteins inside the polymers’ amphiphilic nanocavities (HBPH-NPs), for the effective detection and treatment of cancer. We formulated theranostic polymeric nanoparticles for the simultaneous encapsulation of a apoptosis-initiating protein Cytochrome c and a near infrared dye ICG to folate-expressing cancer cell cells. The potential therapeutic property of these nanoparticles was demonstrated by the induction of apoptosis upon intracellular delivery. Considering that these theranostic nanoparticles can carry an endogenous cellular apoptotic initiator (Cytochrome c) and a fluorescent tag (ICG) commonly used in the clinic, their use and potential translation into the clinic is anticipated, facilitating the monitoring of tumor regression.
D. Multi-step organic synthesis of biodegradable dendrimers, capable of encapsulating therapeutic drugs: A new frontier in the synthetic dendrimer-based drug delivery system for ovarian cancer treatment.
Facile synthesis of 3rd generation polyurethane dendrimer involves more than 10 steps organic synthesis with several air and moisture sensitive reactions. The O-alkylation of Bis-MPA was performed for the first time without forming the cyclic bi-products. Convergent growth approach used to synthesize the dendrimer. The use of acyl azide approach has many salient features such as a) quantitative in situ thermal deprotection of the acyl azide to generate the reactive isocyanate functionality; b) the side product for the thermal deprotection step is the gaseous nitrogen and c) tolerance to allyl surface functional groups making it easier to synthesize various dendrimers with different surface functionality. The synthesized water-dispersed dendrimer nanoparticles were found to be non-toxic when treated with human ovarian cancer cells. The nanoparticles were capable of encapsulating therapeutic anti-cancer drugs; doxorubicin, benomyl, BEZ235 inhibitor and paclitaxel and optical dyes; DiI, DiR for the targeted detection and treatment of ovarian cancers. Surface functional groups were easily available to create a library of targetable theranostic dendrimer-based drug delivery systems, to prevent killing healthy tissues.
PROJECT 2: Novel activatable theranostic probes for the targeted optical detection, MR imaging and treatment of ovarian, lung and cervical cancer.
A. Small molecule-based activatable prodrugs for the detection and treatment of lung cancer. Published in JACS 2011, 133, 16680.
Design and synthesis of a glutathione activatable fluorescent prodrug for dual targeted imaging and treatment of Lung Cancer. The synthesized new probe consists of the therapeutic drug Doxorubicin and receptor targeting ligand Folate. We discovered that the cytotoxicity and fluorescence property of Doxo are quenched (OFF state) when connected with Folic acid. The probe with the disulfide linker (Figure 1A and 1C, Doxo-S-S-Fol) gets activated (ON state) by the intracellular glutathione (GSH), leading to fluorescence emission (optical imaging) and target-specific cytotoxicity (cancer treatment). In contrast, the non-cleavable probe Doxo-C-C-Fol remains quenched showing no migration to the nucleus and therefore no toxicity to the cancer cells. Results also confirmed that the sustained cytotoxicity of the released Doxo-SH derivative is compared to free Doxo. In our novel design, the folic acid acted as both a targeting ligand for the folate receptor as well as a quencher for doxorubicin’s fluorescence. Finally, the excellent plasma stability of the disulfide linker would make our activatable Doxo-S-S-Fol probe suitable in clinical settings.
B. Activatable magnetic nanoprobes for the targeted MR Imaging and treatment of cervical cancer. Published ACS Nano 2012, 6, 7281.
I have applied my organic synthesis expertise to develop a novel gadolinium-encapsulating iron oxide nanoparticle-based activatable NMR/MRI nanoprobe for the targeted detection and treatment of acidic tumors. Developed a magnetic nanoprobe, where the Gd’s T1 magnetic relaxation is quenched by iron oxide core, a strong T2 agent. After receptor-mediated internalization, the probe becomes MRI active due to the release of Gd-DTPA complex and subsequently, the released drug used for the treatment of cancer. Our results also demonstrated that the folate-receptor mediated internalization and the subsequent lysosomal acidic pH-induced intracellular release of Gd-DTPA complex resulted in an enhanced 1/T1 MR signal. This new activatable technology will bring sophisticated tools for the in vivo MR Imaging of acidic tumors while visualizing the drug’s homing. Confocal images showed the internalization (A) and killing (B) of human cervical cancers.
C. Environment-responsive nanophores for therapy and treatment monitoring via molecular MRI quenching. Published in Nature Communications, 2014.
The effective delivery of therapeutics to disease sites significantly contributes to drug efficacy, toxicity and clearance. Here, we used the clinically approved iron oxide nanoparticles (Ferumoxytol) that can be utilized to carry one or multiple drugs. These so called ‘nanophores’ retain their cargo within their polymeric coating through weak electrostatic interactions and release it in slightly acidic conditions (pH 6.8 and below).
The loading of drugs increases the nanophores’ transverse T2 and longitudinal T1 nuclear magnetic resonance (NMR) proton relaxation times, which is proportional to amount of carried cargo. Chemotherapy with translational nanophores is more effective than the free drug in vitro and in vivo, without subjecting the drugs or the carrier nanoparticle to any chemical modification. Evaluation of cargo incorporation and payload levels in vitro and in vivo can be assessed via benchtop magnetic relaxometers, common NMR instruments or magnetic resonance imaging scanners.
D. THERANOSTIC IRON OXIDE NANOPARTICLES AS DRUG DELIVERY SYSTEM. Targeted detection, MR Imaging and treatment of cancer. Published in Small 2009, 5, 1862.
A biocompatible, multimodal and theranostic functional IONPs was synthesized using a novel water-based method and exerted excellent properties for targeted cancer therapy, optical and magnetic resonance imaging (MRI). For the first time, a facile, modified solvent diffusion method is used for the co-encapsulation of both an anti-cancer drug and near infrared dyes. The resulting folate-decorated theranostic nanoparticles could allow for targeted optical/MR-imaging and targeted killing of folate-expressing cancer cells. We anticipate that this multimodal (magnetic and fluorescent) and multifunctional (imaging and therapeutic) IONPs will open many exciting opportunities for the targeted delivery of therapeutic agents to tumors. In addition, the dual optical and magnetic properties of the synthesized nanoparticles will allow for the dual fluorescence- and MR-based imaging and monitoring of drug efficacy. All these positive attributes make our IONPs a promising drug delivery vehicle for further in vivo evaluation.
近期论文
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C. Kaittanis, T. M. Shaffer, A. Ogirala, S. Santra, J. M. Perez, G. Chiosis, Y. Li, L. Josephson, J. Grimm. “Environment-responsive nanophores for therapy and treatment monitoring via molecular MRI quenching” Nature Communications 2014, 5:3384 doi: 10.1038/ncomms4384 (online). (I.F. 10.01)
Santra, S. Jativa, D. J. Kaittanis, C. Normand, G. Grimm, J. Perez, J. M. “Gadolinium-Encapsulating Iron Oxide Nanoprobes as Activatable NMR/MRI Contrast Agent” ACS Nano 2012, 6, 7281. (I.F. 12.06)
Boohaker, R. Zhang, G. Lee, M. Nemec, K. Santra, S. Perez, J. Manuel; Khaled, A. "Rational Development of a Cytotoxic Peptide to Trigger Cell Death" Molecular Pharmaceutics 2012, 9, 2080-2093. (I.F. 4.57)
C. Kaittanis, H. Boukhriss, S. Santra, J. F. Valentine, S. A. Naser, J M. Perez. “Hybridizing magnetic relaxation nanosensors facilitate the rapid and sensitive detection of an intracellular pathogen in human peripheral leukocytes” PLoS One, 2012, 7, e35326. (I.F. 4.4)
*Featured in Genetic Engineering and Biotechnology NewsMagazine. *Featured in www.nano.gov website of National Nanotechnology Initiative group. *Posted on National Institute of General Medical Science (NIH) website. *Posted on Sciencedaily.com website. *Posted on Europapress.com website. *Posted on Eurekalert.com website. *Posted on today.ucf.com website. * Interviewed on FOX 35 news channel.
C. Kaittanis, S. Santra, A. Asati, J. M. Perez. “A Cerium Oxide Nanoparticle-based Device for the Detection of Chronic Inflammation via Optical and Magnetic Resonance Imaging” Nanoscale 2012, 4, 2117-2123. (I.F. 6.23)
S. Santra, C. Kaittanis, O. J. Santiesteban, J. M. Perez “Cell-Specific, Activatable and Theranostic Prodrug for Dual Targeted Cancer Imaging and Therapy” J. Am. Chem. Soc. 2011, 133, 16680-16688. (I.F. 10.67)
S. Santra, C. Kaittanis, O. J. Santiesteban, J. M. Perez “Trifunctional Targeting” ACS Chem. Biol. (Spotlight), 2011, 6, 1143-1143. (I.F. 6.44)
S. Santra,* J. M. Perez “Facile, One-Step, Selective N-Alkylation of Amino Acids: Novel Polyamino Acid-Based Theranostic Nanoagents for Targeted Cancer Therapy” Biomacromolecules 2011, 12, 3917-3927 (I.F. 5.47). * Corresponding Author.
C. Kaittanis, S. Santra, O. J. Santiesteban, T. Henderson, J. M. Perez “The Assembly State between Magnetic Nanosensors and their Targets Orchestrates their Magnetic Relaxation Response” J. Am. Chem. Soc. 2011, 133, 3668-3676. (I.F. 10.67)
A. Asati, C. Kaittanis, S. Santra, J. M. Perez. “pH-Tunable Oxidase-Like Activity of Cerium Oxide Nanoparticles Achieving Sensitive Fluorigenic Detection of Cancer Biomarkers at Neutral pH” Anal. Chem. 2011, 83, 2547-2553. (I.F. 5.69)
C. Kaittanis, T. Banerjee, S. Santra, O. J. Santiesteban, K. Teter, J. M. Perez. “Identification of Molecular-Mimicry-Based Ligands for Cholera Diagnostics using Magnetic Relaxation” Bioconjugate Chemistry, 2011, 22, 307-314. (I.F. 5.37)
A. Asati, S. Santra, C. Kaittanis, J. M. Perez. “Surface chemistry-dependent cell localization and cytotoxicity of cerium oxide nanoparticles” ACS Nano, 2010, 4, 5321-5331. (I.F. 12.06)
S. Santra, C. Kaittanis, J. M. Perez. “Cytochrome c Encapsulating Theranostic Nanoparticles: A Novel Bifunctional System for targeted delivery of therapeutic membrane-impermeable proteins to tumors and imaging of cancer therapy” Molecular Pharmaceutics, 2010, 7, 1209-1222. (I.F. 4.57)
Kaittanis, C., Santra, S., Perez, J. M. Emerging nanotechnology-based strategies for the identification of microbial Adv. Drug Deliv. Rev. 2010, 62, 408. (I.F. 12.88)
Santra, S., Kaittanis, C., Perez, J. M. Aliphatic Hyperbranched Polyester: A New Building Block in the Construction of Multifunctional Nanoparticles and Nanocomposites. Langmuir 2010, 26, 5364. (I.F. 4.18)
Santra, S., Kaittanis C., Grimm J. and Perez J. M. Drug/Dye-Loaded, Multifunctional Iron Oxide Nanoparticles for Combined Targeted Cancer Therapy and Dual Optical/MR-Imaging, Small 2009, 5, 1862. (I.F. 8.34) *Posted on National Institute of General Medical Science (NIH) website *Invited for an interview in TV media coverage. *Posted on Sciencedaily.com website.
Asati, A., Santra, S., Kaittanis, C., Nath, S., Perez, J. M. Oxidase-like activity of polymer-coated cerium oxide nanoparticles. Angew. Chem. Int. Ed. Engl. 2009, 48, 2308. (I.F. 13.45)
* Featured as very important paper *Selected for cover picture of the journal *Featured in ACS Chemical & Engineering News Magazine *Invited by ACS Communication office for Media coverage *Posted on National Institute of General Medical Science (NIH) website.
Kaittanis, C., Santra. S., Perez, J. M. Role of nanoparticle valency in the nondestructive magnetic-relaxation-mediated detection and magnetic isolation of cells in complex media. J. Am. Chem. Soc. 2009, 131, 12780. (I.F. 10.67)
S. Santra and A. Kumar. “Facile synthesis of aliphatic hyperbranched polyesters based on diethylmalonate and their irreversible molecular encapsulation” Chem. Comm. 2004, 2126. (I.F. 6.37)
A. Kumar, A. Q. Contractor, A. V. Ambade, T. Ranganathan, K. Krishnamoorthy, S. P. Mishra, U. P. Ojha, S. Santra, M. Kanungo “Novel approaches for novel materials” Int. J. Plast. Tech. 2003, 6, 73.
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