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Mehanizmi vstopa nanodelcev v celice in njihov vpliv na dostavljanje učinkovin
Teskač, Karmen (Author), Kocbek, Petra (Author), Erdani-Kreft, Mateja (Author), Kristl, Julijana (Author)

URLURL - Presentation file, Visit http://vestnik.szd.si/index.php/vestnik/article/view/765/681 This link opens in a new window

Abstract
Nanodelci (ND) so dostavni nosilni sistemi nanometerskih velikosti. V zadnjih letih so se izkazali kot pomembna novost v sodobni medicini, tako na področju diagnosticiranja kot tudi zdravljenja. Ker so mehanizmi privzema ND v celice različni, pot pa je odvisna od njihovih lastnosti, je za doseganje optimalnih učinkov zdravljenja ključnega pomena, da poznamo medsebojne povezave med privzemom in lastnostmi ND. V članku predstavljamo mehanizme prehoda ND v celice in znotrajcelično dogajanje. ND lahko vstopajo v celice po fagocitozni poti ali po nefagocitoznih poteh (z endocitozo, posredovano s klatrini oz. s kaveolini, z makropinocitozo, po drugih endocitoznih poteh). Pot privzema ND vcelice narekuje mesto sproščanja učinkovine, ki se lahko odvija v kislem in zencimi bogatem okolju lizosomov ali pa ga ND obidejo in sprostijo učinkovino v citosolu ali drugem organelu. To lahko dosežemo s skrbno načrtovano izbiro sestavin za ND in ob upoštevanju njihovih fizikalno-kemijskih lastnosti (velikost, oblika, površinske lastnosti). Fagocitoza je pogosto neželen pojav,saj je njen glavni namen odstranitev tujkov iz telesa, zato je tako privzeta učinkovina največkrat izgubljena. Temu se lahko izognemo z izdelavo čim manjših delcev s hidrofilno ovojnico, najuspešnejše pa je, da na površino pripnemo ligande, ki usmerijo privzem po nefagocitozni poti. Vedenje o načinu privzema ND v celice je torej bistvenega pomena za načrtovanje dostave učinkovin na želeno mesto v celicah, kar lahko znatno izboljša stabilnost ND in ohrani biološko aktivnost predvsem zelo občutljivih učinkovin

Language:Slovenian
Keywords:nanodelci, nanozdravila, endocitoza, fagocitoza, ciljana dostava, protitumorsko zdravljenje
Work type:Not categorized (r6)
Tipology:1.02 - Review Article
Organization:FFA - Faculty of Pharmacy
Year:2012
Publisher:Slovensko zdravniško društvo
Number of pages:str. 225-235
Numbering:Letn. 81, št. 3
UDC:576.3:620.3
ISSN on article:1318-0347
COBISS.SI-ID:3220849 Link is opened in a new window
Views:637
Downloads:113
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Record is a part of a journal

Title:Zdravniški vestnik
Publisher:Slovensko zdravniško društvo
ISSN:1318-0347
COBISS.SI-ID:32893696 This link opens in a new window

Secondary language

Language:English
Title:Mechanisms of cellular uptake of nanoparticles and their effect on drug delivery
Abstract:
In the field of diagnosis and treatment in contemporary medicine, nanoparticles (NPs) are an important novelty. They are drug delivery systems on the nanometer scale, whose uptake mechanisms and routes of internalization differ, depending on their properties. For successful treatment, it is crucially important to understand the interplay between uptake mechanisms and NP properties. In this article mechanisms of NP uptake and the subsequent intracellular events are presented. NPs can enter cells via phagocytotic or non-phagocytotic pathways (clathrin-mediated endocytosis, caveolae- mediated endocytosis, macropinocytosis, other endocytotic pathways). The route of internalization determines the site of drug release, which can be in the acidic and enzyme rich environment of lysosomes, or NPs avoid this compartmentand release drug in the cytosol or another organelle. This process can be controlled by a careful selection of NP ingredients and precise design of their physico-chemical properties (size, shape, surface properties). Phagocytosis is generally undesirable, since its main purpose is the elimination of foreign materials from the body, and therefore the drug taken up in this way is usually lost. To avoid this internalization mechanism, the particles should be small showing a hydrophilic surface. However, the most successful approach is to attach ligands to the NP surface, which governs the uptake through non-phagocytotic mechanisms. Knowledge about cellular uptake mechanisms is crucial for predicting drug delivery to the target site in the cell, since it can lead to better stability of NPs and preserved biological activity of labile drugs


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