Silver nanoparticles for cancer research
Kuupäev
2017-10-17
Autorid
Ajakirja pealkiri
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Abstrakt
Vähktõve efektiivse ravi tagamine on kaasaegsele meditsiinile jätkuvalt suureks väljakutseks. Kuigi nanoravimitega on viimase 20 aasta jooksul saavutatud mõningast edu vähiravi kõrvaltoimete vähendamisel, ei ole see ravimiklass osutunud loodetud imerohuks ega suurendanud patsientide elumust. Praegu kliinilises kasutuses olevad nanoravimid akumuleeruvad kasvajalistes kudedes passiivselt. Vähirakke selektiivselt ära tundvaid nanoosakesi testitakse arvukates prekliinilistes ja kliinilistes uuringutes. Vähirakke ära tundvate moodulite lisamine terapeutilistele nanoosakestele võimaldab parandada akumulatsiooni vähikoes ning seeläbi võimaldada efektiivsemat ravi ning vähendada kõrvaltoimeid. Üks võimalus nanoosakeste suunamiseks on kasutada in vivo faagidisplei meetodi abil avastatud kullerpeptiidide. Selliste peptiidide avastamiseks süstitakse vähi-hiiri bakteriofaagi kattevalgul kuvatud peptiidi-raamatukogudega. Kasvajakoes üle-esindatud peptiidi-faagide sekveneerimine aitab seejärel tuvastada koeselektiivsed kullerpeptiidid. Kullerpeptiidide ja teiste nanoosakeste pinnamodifikatsioonide mõju hindamiseks oleks palju abi mudel-nanoosakeste platvormist, mida on lihtne kasutada, mikroskoopiliselt uurida ja kvantifitseerida. Kuna enamik ravimeid peavad ravitoime avaldumiseks sisenema rakku, võiks üks nanoosakeste platvormi kasulik omadus olla võimalus eristada intra- ja ekstratsellulaarseid osakesi. Hõbeda nanoosakestel (AgNP) on olemas kõik eelpool soovitud omadused. AgNP võimendavad neile kinnitatud värvainete fluorestsentsi, neil on optilisel tuvastamisel kõrge ekstinktsioonikoefitsient ning nendega on võimalik siduda lühikesi peptiide. Veelgi enam, AgNP lahustuvad kiiresti ja täielikult mittetoksilises metalse hõbeda söövituslahustis; see võimaldab rakuväliste osakeste lahustamist, mõjutamata rakusiseseid osakesi. AgNP on võimalik valmistada hõbeda puhastest isotoopidest, võimaldamaks osakeste isotoopset tuvastamist ja kvantifitseerimist massispektromeetria abil.
Cancer continues to be a challenge to modern medicine. While nanotherapeutics have had some success in the past 20 years at reducing side effects and improving patient tolerance of treatment, they have not been the silver bullet that was hoped for and have not increased overall survival in patients. Clinical nanotherapeutics so far only target tumors through passive accumulation from blood circulation. Nanoparticles (NPs) targeted to tumors have yet to be approved although some are in clinical trials. It is hoped that with added targeting groups on therapeutic nanoparticles more effective treatment is possible. One way to target NPs is through the use of homing peptides, discovered by phage display, conjugated to their surface. Phage display uses massively diverse libraries of peptides that are displayed on a bacteriophage coat protein. The library can be injected systemically and then the peptide-phages that have homed to a tumor can be recovered and sequenced in order to identify homing peptides. These peptides are well suited to being synthesized and conjugated to a nanoparticle, which mimics the bacteriophage, itself a biological nanoparticle. Peptides targeting various cancers have already been discovered through phage display and some have been used successfully on nanoparticles in the pre-clinical setting. In order to validate these peptides a nanoparticle platform is necessary which is similar to the phage, but easier to use, identify microscopically, and quantify. Another useful feature of a nanoparticle platform would be to make it possible to identify intra- and extracellular particles, since most therapeutics must be delivered inside a cell in order to work. Silver nanoparticles (AgNPs) are able to provide all of the above tools. They enhance conjugated dyes, effectively scatter light for optical detection, and enable simple peptide conjugation. A biocompatible solution was developed, to dissolve the AgNPs, to make it possible to distinguish between particles taken in by cells and those that remain outside. The AgNPs were developed further to evaluate accessible target molecules on the surface of cancer cells. This would facilitate classifying different cancers to guide the selection of an appropriate treatment. Additionally, the particle composition was altered so as to enable detection and quantification of AgNPs from cells or tissues by mass spectrometry.
Cancer continues to be a challenge to modern medicine. While nanotherapeutics have had some success in the past 20 years at reducing side effects and improving patient tolerance of treatment, they have not been the silver bullet that was hoped for and have not increased overall survival in patients. Clinical nanotherapeutics so far only target tumors through passive accumulation from blood circulation. Nanoparticles (NPs) targeted to tumors have yet to be approved although some are in clinical trials. It is hoped that with added targeting groups on therapeutic nanoparticles more effective treatment is possible. One way to target NPs is through the use of homing peptides, discovered by phage display, conjugated to their surface. Phage display uses massively diverse libraries of peptides that are displayed on a bacteriophage coat protein. The library can be injected systemically and then the peptide-phages that have homed to a tumor can be recovered and sequenced in order to identify homing peptides. These peptides are well suited to being synthesized and conjugated to a nanoparticle, which mimics the bacteriophage, itself a biological nanoparticle. Peptides targeting various cancers have already been discovered through phage display and some have been used successfully on nanoparticles in the pre-clinical setting. In order to validate these peptides a nanoparticle platform is necessary which is similar to the phage, but easier to use, identify microscopically, and quantify. Another useful feature of a nanoparticle platform would be to make it possible to identify intra- and extracellular particles, since most therapeutics must be delivered inside a cell in order to work. Silver nanoparticles (AgNPs) are able to provide all of the above tools. They enhance conjugated dyes, effectively scatter light for optical detection, and enable simple peptide conjugation. A biocompatible solution was developed, to dissolve the AgNPs, to make it possible to distinguish between particles taken in by cells and those that remain outside. The AgNPs were developed further to evaluate accessible target molecules on the surface of cancer cells. This would facilitate classifying different cancers to guide the selection of an appropriate treatment. Additionally, the particle composition was altered so as to enable detection and quantification of AgNPs from cells or tissues by mass spectrometry.
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Märksõnad
nanomeditsiin, vähk (med.), meditsiiniuuringud, farmakoteraapia, nanoosakesed, hõbe, ravimikandjad, ravimite transport organismis, rakku sisenevad peptiidid, nanomedicine, cancer (medicine), medical research, pharmacotherapy, nanoparticles, silver, drug carriers, drug transport, cell-penetrating peptides