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Cancer Nanotheranostics - What Have We Learnd So Far?
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Condeetal. Biofunctionalizationandsurfacechemistryof inorganicnanoparticles FIGURE2|Polyvalent PEGylated gold nanoparticles. (A) Bioconjugation of the surface-modified gold nanoparticles with different thiol-PEG layer composition (SH-EG(7)-CH2-COOH and SH-(CH2)3-CONH-EG(6)-CH2-N3), TAT peptide and thiol-dsRNA oligonucleotide. (B) Mechanism for the enhancement of the dsRNA loading on AuNPs functionalized with PEG chains and TAT peptide. The azide group has a resonant structure with a positively polarized behavior that can attach the negatively charged thiolated oligonucleotide to the gold surface. The azide-containing chain also encloses an amide group near the gold surface that could play a role in approaching the thiol group of the oligonucleotide to the gold surface. This amide group could form a hydrogen bond with one of the hydroxyl groups of the ribose group near the thiol group on the oligonucleotide. (C) Determination of the number of TAT chains bound to AuNPs by the EDC reaction as a function of the initial peptide concentration in the reaction mixture. Blue bars AuNP@COOH/N3 and red bars AuNP@COOH. (D) Loading of thiolated oligonucleotide (HS-dsRNA) on AuNPs functionalized with TAT peptide and with both PEG-azide and PEG-COOH and only with PEG-COOH. Blue bars AuNP@COOH/N3 and red bars AuNP@COOH (Sanz et al., 2012). Reproduced with permission from Sanz et al. (2012), Copyright 2013. stimulus-sensitive detachablePEG is a possible solution toover- come these drawbacks, so that cargoes can be released or other ligands unveiled in response tomicroenvironmental conditions. For instance,Harris et al. functionalizedMNPswithaPEGteth- eredbyanMMP-2cleavable substrate (Harris et al., 2008),being MMP-2 a protease upregulated in angiogenesis andmetastasis. OnceNPs reached the tumor, the polymer was cleaved, unveil- ing the cell penetratingpeptide, resulting in increaseduptakeby cellswhencomparedtonon-cleavablePEG. Fluorescentdyes Several studies report on themodulation of fluorophores at the vicinity of nanoparticles (Kang et al., 2011; Rosa et al., 2011), which has found application in a variety of systems to detect biologically relevant targets. Severalmethodsbasedon thequenchingoffluorescencehave been proposed for DNA detection consisting of fluorophore- labeled ssDNAelectrostatically adsorbedontoAuNPs (Rayet al., 2006), where the presence of a complementary target triggers desorption of the newly formed dsDNA from the nanostruc- tures due to the electrostatic variation between ssDNA and dsDNA,andfluorescenceemission is restored.Also,fluorescence quenching of fluorophores close to gold nanocarriers function- alized with thiol-modified oligonucleotides has been explored in different conformations (Wu et al., 2006; Tang et al., 2008). Tang et al. proposed amethod to probe hydroxyl radicals using an AuNP-oligonucleotide-FAM systemwhere the hydroxyl rad- ical promotes strand breakage and consequent release of FAM, restoring the previously quenched fluorescence (see Figure3) (Tang et al., 2008). The same quenching mechanism was used to detect specific DNA strands using two probes (one with an AuNP label and another labeledwithTAMRA) that hybridize to twoDNA sequences near each other (Wuet al., 2006), bringing thefluorophore andAuNPclose enough toquenchfluorescence emission. Proteins have also been probed through nanoparticle fluorescence-mediated systems, especially for protein detection via quenching, through the interaction with fluorescent AuNPs (Mayilo et al., 2009; He et al., 2010; Lacerda et al., 2010). Due to their efficient proximity-dependent fluorescence quenching they can be used per se or as part ofmore elaborate conjugates (i.e., withQDs) (Pons et al., 2007).One example is thework of De et al. where the interaction between AuNPs and the green fluorescent protein (GFP) was employed to detect proteins in www.frontiersin.org July2014 |Volume2 |Article48 | 12
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Cancer Nanotheranostics What Have We Learnd So Far?
Title
Cancer Nanotheranostics
Subtitle
What Have We Learnd So Far?
Authors
João Conde
Pedro Viana Baptista
Jesús M. De La Fuente
Furong Tian
Editor
Frontiers in Chemistry
Date
2016
Language
English
License
CC BY 4.0
ISBN
978-2-88919-776-7
Size
21.0 x 27.7 cm
Pages
132
Keywords
Nanomedicine, Nanoparticles, nanomaterials, Cancer, heranostics, Immunotherapy, bioimaging, Drug delivery, Gene Therapy, Phototherapy
Categories
Naturwissenschaften Chemie
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