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

0460351 - ÚMCH 2017 RIV GB eng J - Článek v odborném periodiku
Studenovský, Martin - Heinrich, A. K. - Lucas, H. - Mueller, T. - Mäder, K. - Etrych, Tomáš
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.
Journal of Bioactive and Compatible Polymers. Roč. 31, č. 4 (2016), s. 348-360. ISSN 0883-9115. E-ISSN 1530-8030
Grant CEP: GA ČR(CZ) GCP207/12/J030; GA ČR(CZ) GA14-12742S; GA MŠMT(CZ) ED1.1.00/02.0109
Institucionální podpora: RVO:61389013
Klíčová slova: HPMA copolymers * reduction-responsive drug release * tumor accumulation
Kód oboru RIV: CD - Makromolekulární chemie
Impakt faktor: 1.310, rok: 2016

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 104kDa), 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.
Trvalý link: http://hdl.handle.net/11104/0260476