Dual fluorescent N-(2-hydroxypropyl) methacrylamide-based conjugates for passive tumor targeting with reduction-sensitive drug release: proof of the concept, tumor accumulation, and biodistribution

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F16%3A00460351" target="_blank" >RIV/61389013:_____/16:00460351 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1177/0883911515618975" target="_blank" >http://dx.doi.org/10.1177/0883911515618975</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1177/0883911515618975" target="_blank" >10.1177/0883911515618975</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Dual fluorescent N-(2-hydroxypropyl) methacrylamide-based conjugates for passive tumor targeting with reduction-sensitive drug release: proof of the concept, tumor accumulation, and biodistribution

Popis výsledku v původním jazyce

In the field of drug delivery, many different carrier systems have been described to date, including nanoparticles, micelles, liposomes, and water-soluble polymer conjugates, where the active compound could be either incorporated non-covalently or linked to its carrier by a degradable chemical bond. In this study, we synthesized, characterized, and investigated the in vivo fate of N-(2-hydroxypropyl)methacrylamide-based polymer conjugates with a drug model bound via a disulfide bond, which is frequently cited in the literature as being completely stable in the bloodstream but readily cleaved after cell internalization. The concept was based on a “dual labeling of N-(2-hydroxypropyl)methacrylamide copolymers with two different fluorescent dyes, where the first dye was linked via a disulfide bond, thus representing a model drug, while the second dye was attached as an amide and served as a label for the polymer carrier. Two conjugates, differing in their molecular weights (30 and 104 kDa), were examined using a multispectral optical imaging technique in athymic nude mice inoculated with HT-29 and DLD-1 human colon carcinoma xenografts. Additionally, necropsied organs and tumors were examined ex vivo to obtain more detailed information about polymer and model drug biodistribution. In vivo results confirmed preferential tumor accumulation for both conjugates. Moreover, different fluorescence patterns for the polymer and drug model were observed in both mice and necropsied tumors, indicating tumor-specific “drug release.

Název v anglickém jazyce

Dual fluorescent N-(2-hydroxypropyl) methacrylamide-based conjugates for passive tumor targeting with reduction-sensitive drug release: proof of the concept, tumor accumulation, and biodistribution

Popis výsledku anglicky

In the field of drug delivery, many different carrier systems have been described to date, including nanoparticles, micelles, liposomes, and water-soluble polymer conjugates, where the active compound could be either incorporated non-covalently or linked to its carrier by a degradable chemical bond. In this study, we synthesized, characterized, and investigated the in vivo fate of N-(2-hydroxypropyl)methacrylamide-based polymer conjugates with a drug model bound via a disulfide bond, which is frequently cited in the literature as being completely stable in the bloodstream but readily cleaved after cell internalization. The concept was based on a “dual labeling of N-(2-hydroxypropyl)methacrylamide copolymers with two different fluorescent dyes, where the first dye was linked via a disulfide bond, thus representing a model drug, while the second dye was attached as an amide and served as a label for the polymer carrier. Two conjugates, differing in their molecular weights (30 and 104 kDa), were examined using a multispectral optical imaging technique in athymic nude mice inoculated with HT-29 and DLD-1 human colon carcinoma xenografts. Additionally, necropsied organs and tumors were examined ex vivo to obtain more detailed information about polymer and model drug biodistribution. In vivo results confirmed preferential tumor accumulation for both conjugates. Moreover, different fluorescence patterns for the polymer and drug model were observed in both mice and necropsied tumors, indicating tumor-specific “drug release.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CD - Makromolekulární chemie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Bioactive and Compatible Polymers

ISSN

0883-9115

e-ISSN

—

Svazek periodika

31

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

13

Strana od-do

348-360

Kód UT WoS článku

000379513200003

EID výsledku v databázi Scopus

2-s2.0-84975730954