247 research outputs found

    Silicon particles as trojan horses for potential cancer therapy

    Get PDF
    [EN] Background: Porous silicon particles (PSiPs) have been used extensively as drug delivery systems, loaded with chemical species for disease treatment. It is well known from silicon producers that silicon is characterized by a low reduction potential, which in the case of PSiPs promotes explosive oxidation reactions with energy yields exceeding that of trinitrotoluene (TNT). The functionalization of the silica layer with sugars prevents its solubilization, while further functionalization with an appropriate antibody enables increased bioaccumulation inside selected cells. Results: We present here an immunotherapy approach for potential cancer treatment. Our platform comprises the use of engineered silicon particles conjugated with a selective antibody. The conceptual advantage of our system is that after reaction, the particles are degraded into soluble and excretable biocomponents. Conclusions: In our study, we demonstrate in particular, specific targeting and destruction of cancer cells in vitro. The fact that the LD50 value of PSiPs-HER-2 for tumor cells was 15-fold lower than the LD50 value for control cells demonstrates very high in vitro specificity. This is the first important step on a long road towards the design and development of novel chemotherapeutic agents against cancer in general, and breast cancer in particular.The authors acknowledge financial support from the following projects FIS2009-07812, MAT2012-35040, PROMETEO/2010/043, CTQ2011-23167, CrossSERS, FP7 MC-IEF 329131, and HSFP (project RGP0052/2012) and Medcom Tech SA. Xiang Yu acknowledges support by the Chinese government (CSC, Nr. 2010691036).Fenollosa Esteve, R.; Garcia-Rico, E.; Alvarez, S.; Alvarez, R.; Yu, X.; Rodriguez, I.; Carregal-Romero, S.... (2014). Silicon particles as trojan horses for potential cancer therapy. Journal of Nanobiotechnology. 12:1-10. https://doi.org/10.1186/s12951-014-0035-7S11012Prasad PN: Introduction to Nanomedicine and Nanobioengineering. Wiley, New York, 2012.Randall CL, Leong TG, Bassik N, Gracias DH: 3D lithographically fabricated nanoliter containers for drug delivery. Adv Drug Del Rev. 2007, 59: 1547-1561. 10.1016/j.addr.2007.08.024.Reibetanz U, Chen MHA, Mutukumaraswamy S, Liaw ZY, Oh BHL, Venkatraman S, Donath E, Neu BR: Colloidal DNA carriers for direct localization in cell compartments by pH sensoring. Biogeosciences. 2010, 11: 1779-1784.Tasciotti E, Liu X, Bhavane R, Plant K, Leonard AD, Price BK, Cheng MM-C, Decuzzi P, Tour JM, Robertson F, Ferrari M: Mesoporous silicon particles as a multistage delivery system for imaging and therapeutic applications. Nat Nano. 2008, 3: 151-157. 10.1038/nnano.2008.34.Park J-H, Gu L, von Maltzahn G, Ruoslahti E, Bhatia SN, Sailor MJ: Biodegradable luminescent porous silicon nanoparticles for in vivo applications. Nat Mater. 2009, 8: 331-336. 10.1038/nmat2398.Hong C, Lee J, Son M, Hong SS, Lee C: In-vivo cancer cell destruction using porous silicon nanoparticles. Anti-Cancer Drugs. 2011, 22: 971-977. 910.1097/CAD.1090b1013e32834b32859cCanham LT: Device Comprising Resorbable Silicon for Boron Capture Neutron Therapy. UK Patent Nr. 0302283.7. Book Device Comprising Resorbable Silicon for Boron Capture Neutron Therapy. UK Patent Nr. 0302283.7 (Editor ed.^eds.). 2003, UK Patent Nr. 0302283.7, CityXiao L, Gu L, Howell SB, Sailor MJ: Porous silicon nanoparticle photosensitizers for singlet oxygen and their phototoxicity against cancer cells. ACS Nano. 2011, 5: 3651-3659. 10.1021/nn1035262.Gil PR, Parak WJ: Composite nanoparticles take Aim at cancer. ACS Nano. 2008, 2: 2200-2205. 10.1021/nn800716j.Gomella LG: Is interstitial hyperthermia a safe and efficacious adjunct to radiotherapy for localized prostate cancer?. Nat Clin Pract Urol. 2004, 1: 72-73. 10.1038/ncpuro0041.Maier-Hauff K, Ulrich F, Nestler D, Niehoff H, Wust P, Thiesen B, Orawa H, Budach V, Jordan A: Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme. J Neuro-Oncol. 2011, 103: 317-324. 10.1007/s11060-010-0389-0.Lal S, Clare SE, Halas NJ: Nanoshell-enabled photothermal cancer therapy: Impending clinical impact. Acc Chem Res. 2008, 41: 1842-1851. 10.1021/ar800150g.Lee C, Kim H, Hong C, Kim M, Hong SS, Lee DH, Lee WI: Porous silicon as an agent for cancer thermotherapy based on near-infrared light irradiation. J Mater Chem. 2008, 18: 4790-4795. 10.1039/b808500e.Osminkina LA, Gongalsky MB, Motuzuk AV, Timoshenko VY, Kudryavtsev AA: Silicon nanocrystals as photo- and sono-sensitizers for biomedical applications. Appl Phys B. 2011, 105: 665-668. 10.1007/s00340-011-4562-8.Jain PK, Huang X, El-Sayed IH, El-Sayed MA: Noble metals on the nanoscale: optical and photothermal properties and some applications in imaging, sensing, biology, and medicine. Acc Chem Res. 2008, 41: 1578-1586. 10.1021/ar7002804.Serda RE, Godin B, Blanco E, Chiappini C, Ferrari M: Multi-stage delivery nano-particle systems for therapeutic applications. Biochim Biophys Acta. 1810, 2011: 317-329.Xu R, Huang Y, Mai J, Zhang G, Guo X, Xia X, Koay EJ, Qin G, Erm DR, Li Q, Liu X, Ferrari M, Shen H: Multistage vectored siRNA targeting ataxia-telangiectasia mutated for breast cancer therapy. Small. 2013, 9: 1799-1808. 10.1002/smll.201201510.Park JS, Kinsella JM, Jandial DD, Howell SB, Sailor MJ: Cisplatin-loaded porous Si microparticles capped by electroless deposition of platinum. Small. 2011, 7: 2061-2069. 10.1002/smll.201100438.Xue M, Zhong X, Shaposhnik Z, Qu Y, Tamanoi F, Duan X, Zink JI: pH-operated mechanized porous silicon nanoparticles. J Am Chem Soc. 2011, 133: 8798-8801. 10.1021/ja201252e.Canham LT: Bioactive silicon structure fabrication through nanoetching techniques. Adv Mater. 1995, 7: 1033-1037. 10.1002/adma.19950071215.Popplewell JF, King SJ, Day JP, Ackrill P, Fifield LK, Cresswell RG, Di Tada ML, Liu K: Kinetics of uptake and elimination of silicic acid by a human subject: a novel application of 32Si and accelerator mass spectrometry. J Inorganic Biochem. 1998, 69: 177-180. 10.1016/S0162-0134(97)10016-2.Shabir Q, Pokale A, Loni A, Johnson DR, Canham LT, Fenollosa R, Tymczenko M, Rodr guez I, Meseguer F, Cros A, Cantarero A: Medically biodegradable hydrogenated amorphous silicon microspheres. Silicon. 2011, 3: 173-176. 10.1007/s12633-011-9097-4.Chen Y, Wan Y, Wang Y, Zhang H, Jiao Z: Anticancer efficacy enhancement and attenuation of side effects of doxorubicin with titanium dioxide nanoparticles. Int J Nanomed. 2011, 6: 2321-2326.Mackowiak SA, Schmidt A, Weiss V, Argyo C, von Schirnding C, Bein T, Bräuchle C: Targeted drug delivery in cancer cells with Red-light photoactivated mesoporous silica nanoparticles. Nano Lett. 2013, 13: 2576-2583. 10.1021/nl400681f.Li Z, Barnes JC, Bosoy A, Stoddart JF, Zink JI: Mesoporous silica nanoparticles in biomedical applications. Chem Soc Rev. 2012, 41: 2590-2605. 10.1039/c1cs15246g.O Mara WC, Herring B, Hunt P: Handbook of Semiconductor Silicon Technology. Noyes Publication, New Jersey, 1990.Mikulec FV, Kirtland JD, Sailor MJ: Explosive nanocrystalline porous silicon and its Use in atomic emission spectroscopy. Adv Mater. 2002, 14: 38-41. 10.1002/1521-4095(20020104)14:13.0.CO;2-Z.Clement D, Diener J, Gross E, Kunzner N, Timoshenko VY, Kovalev D: Highly explosive nanosilicon-based composite materials. Phys Stat Sol A. 2005, 202: 1357-1359. 10.1002/pssa.200461102.Canham LT: Silicon quantum wire array fabrication by electrochemical and chemical dissolution of wafers. Appl Phys Lett. 1990, 57: 1046-1049. 10.1063/1.103561.Canham LT: Properties of Porous Silicon. INSPEC, United Kindom, 1997.Heinrich JL, Curtis CL, Credo GM, Sailor MJ, Kavanagh KL: Luminescent colloidal silicon suspensions from porous silicon. Science. 1992, 255: 66-68. 10.1126/science.255.5040.66.Littau KA, Szajowski PJ, Muller AJ, Kortan AR, Brus LE: A luminescent silicon nanocrystal colloid via a high-temperature aerosol reaction. J Phys Chem. 1993, 97: 1224-1230. 10.1021/j100108a019.Menz WJ, Shekar S, Brownbridge GPE, Mosbach S, Kōrmer R, Peukert W, Kraft M: Synthesis of silicon nanoparticles with a narrow size distribution: a theoretical study. J Aerosol Sci. 2012, 44: 46-61. 10.1016/j.jaerosci.2011.10.005.Swihart MT, Girshick SL: Thermochemistry and kinetics of silicon hydride cluster formation during thermal decomposition of silane. J Phys Chem B. 1998, 103: 64-76. 10.1021/jp983358e.Fenollosa R, Ramiro-Manzano F, Tymczenko M, Meseguer F: Porous silicon microspheres: synthesis, characterization and application to photonic microcavities. J Mater Chem. 2010, 20: 5210-5214. 10.1039/c0jm00079e.Ramiro-Manzano F, Fenollosa R, Xifré-Pérez E, Garín M, Meseguer F: Porous silicon microcavities based photonic barcodes. Adv Mater. 2011, 23: 3022-3025. 10.1002/adma.201100986.Kastl L, Sasse D, Wulf V, Hartmann R, Mircheski J, Ranke C, Carregal-Romero S, Martínez-López JA, Fernández-Chacón R, Parak WJ, Elsasser HP, Rivera-Gil P: Multiple internalization pathways of polyelectrolyte multilayer capsules into mammalian cells. ACS Nano. 2013, 7: 6605-6618. 10.1021/nn306032k.Schweiger C, Hartmann R, Zhang F, Parak W, Kissel T, Rivera_Gil P: Quantification of the internalization patterns of superparamagnetic iron oxide nanoparticles with opposite charge. J Nanobiotech. 2012, 10: 28-10.1186/1477-3155-10-28.Sanles-Sobrido M, Exner W, Rodr guez-Lorenzo L, Rodríguez-Gonzílez B, Correa-Duarte MA, Álvarez-Puebla RA, Liz-Marzán LM: Design of SERS-encoded, submicron, hollow particles through confined growth of encapsulated metal nanoparticles. J Am Chem Soc. 2009, 131: 2699-2705. 10.1021/ja8088444.Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J: Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011, 365: 1273-1283. 10.1056/NEJMoa0910383.Agus DB, Gordon MS, Taylor C, Natale RB, Karlan B, Mendelson DS, Press MF, Allison DE, Sliwkowski MX, Lieberman G, Kelsey SM, Fyfe G: Phase I clinical study of pertuzumab, a novel HER dimerization inhibitor, in patients with advanced cancer. J Clin Oncol. 2005, 23: 2534-2543. 10.1200/JCO.2005.03.184.Colombo M, Mazzucchelli S, Montenegro JM, Galbiati E, Corsi F, Parak WJ, Prosperi D: Protein oriented ligation on nanoparticles exploiting O6-alkylguanine-DNA transferase (SNAP) genetically encoded fusion. Small. 2012, 8: 1492-1497. 10.1002/smll.201102284.Franklin MC, Carey KD, Vajdos FF, Leahy DJ, de Vos AM, Sliwkowski MX: Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell. 2004, 5: 317-328. 10.1016/S1535-6108(04)00083-2.Paris L, Cecchetti S, Spadaro F, Abalsamo L, Lugini L, Pisanu ME, Lorio E, Natali PG, Ramoni C, Podo F: Inhibition of phosphatidylcholine-specific phospholipase C downregulates HER2 overexpression on plasma membrane of breast cancer cells. Breast Cancer Res. 2010, 12: R27-10.1186/bcr2575.Fenollosa R, Meseguer F, Tymczenko M: Silicon colloids: from microcavities to photonic sponges. Adv Mater. 2008, 20: 95-98. 10.1002/adma.200701589.Jasinski JM, Gates SM: Silicon chemical vapor deposition one step at a time: fundamental studies of silicon hydride chemistry. Acc Chem Res. 1991, 24: 9-15. 10.1021/ar00001a002.Xiao Q, Liu Y, Qiu Y, Zhou G, Mao C, Li Z, Yao Z-J, Jiang S: Potent antitumor mimetics of annonaceous acetogenins embedded with an aromatic moiety in the left hydrocarbon chain part. J Med Chem. 2010, 54: 525-533. 10.1021/jm101053k.Allman SA, Jensen HH, Vijayakrishnan B, Garnett JA, Leon E, Liu Y, Anthony DC, Sibson NR, Feizi T, Matthews S, Davis BG: Potent fluoro-oligosaccharide probes of adhesion in toxoplasmosis. ChemBioChem. 2009, 10: 2522-2529. 10.1002/cbic.200900425.Chambers DJ, Evans GR, Fairbanks AJ: Elimination reactions of glycosyl selenoxides. Tetrahedron. 2004, 60: 8411-8419. 10.1016/j.tet.2004.07.005.Tomabechi Y, Suzuki R, Haneda K, Inazu T: Chemo-enzymatic synthesis of glycosylated insulin using a GlcNAc tag. Bioorg Med Chem. 2010, 18: 1259-1264. 10.1016/j.bmc.2009.12.031.Pastoriza-Santos I, Gomez D, Perez-Juste J, Liz-Marzan LM, Mulvaney P: Optical properties of metal nanoparticle coated silica spheres: a simple effective medium approach. Phys Chem Chem Phys. 2004, 6: 5056-5060. 10.1039/b405157b

    The Mayer-Rokitansky-Küster-Hauser syndrome (congenital absence of uterus and vagina) – phenotypic manifestations and genetic approaches

    Get PDF
    The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome affects at least 1 out of 4500 women and has for a long time been considered as a sporadic anomaly. Congenital absence of upper vagina and uterus is the prime feature of the disease which, in addition, is often found associated with unilateral renal agenesis or adysplasia as well as skeletal malformations (MURCS association). The phenotypic manifestations of MRKH overlap various other syndromes or associations and thus require accurate delineation. Since MRKH manifests itself in males, the term GRES syndrome (Genital, Renal, Ear, Skeletal) might be more appropriate when applied to both sexes. The MRKH syndrome, when described in familial aggregates, seems to be transmitted as an autosomal dominant trait with an incomplete degree of penetrance and variable expressivity. This suggests the involvement of either mutations in a major developmental gene or a limited chromosomal deletion. Until recently progress in understanding the genetics of MRKH syndrome has been slow, however, now HOX genes have been shown to play key roles in body patterning and organogenesis, and in particular during genital tract development. Expression and/or function defects of one or several HOX genes may account for this syndrome
    corecore