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基于聚丙烯酸纳米凝胶的靶向放射性同位素载体的合成与性质

Synthesis and Properties of Targeted Radioisotope Carriers Based on Poly(Acrylic Acid) Nanogels.

作者信息

Matusiak Małgorzata, Rurarz Beata P, Kadłubowski Sławomir, Wolszczak Marian, Karczmarczyk Urszula, Maurin Michał, Kolesińska Beata, Ulański Piotr

机构信息

Institute of Applied Radiation Chemistry, Faculty of Chemistry, Lodz University of Technology, Wróblewskiego 15, 93-590 Lodz, Poland.

National Centre for Nuclear Research, Radioisotope Centre POLATOM, Andrzeja Sołtana 7, 05-400 Otwock, Poland.

出版信息

Pharmaceutics. 2021 Aug 11;13(8):1240. doi: 10.3390/pharmaceutics13081240.

DOI:10.3390/pharmaceutics13081240
PMID:34452201
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8400054/
Abstract

Radiation crosslinking was employed to obtain nanocarriers based on poly(acrylic acid)-PAA-for targeted delivery of radioactive isotopes. These nanocarriers are internally crosslinked hydrophilic macromolecules-nanogels-bearing carboxylic groups to facilitate functionalization. PAA nanogels were conjugated with an engineered bombesin-derivative-oligopeptide combined with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate chelating moiety, aimed to provide selective radioligand transport. 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium (DMTMM) toluene-4-sulfonate was used as the coupling agent. After tests on a model amine-p-toluidine-both commercial and home-synthesized DOTA-bombesin were successfully coupled to the nanogels and the obtained products were characterized. The radiolabeling efficiency of nanocarriers with Lu, was chromatographically tested. The results provide a proof of concept for the synthesis of radiation-synthesized nanogel-based radioisotope nanocarriers for theranostic applications.

摘要

采用辐射交联法制备了基于聚（丙烯酸）-PAA-的纳米载体，用于放射性同位素的靶向递送。这些纳米载体是内部交联的亲水性大分子——纳米凝胶，带有羧基以促进功能化。PAA纳米凝胶与一种工程化的铃蟾肽衍生物寡肽结合，该寡肽与1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸螯合部分结合，旨在提供选择性放射性配体转运。4-(4,6-二甲氧基-1,3,5-三嗪-2-基)-4-甲基吗啉鎓（DMTMM）对甲苯磺酸盐用作偶联剂。在对模型胺对甲苯胺进行测试后，商业合成和自制的DOTA-铃蟾肽均成功偶联到纳米凝胶上，并对所得产物进行了表征。通过色谱法测试了纳米载体与镥的放射性标记效率。这些结果为合成用于治疗诊断应用的基于辐射合成纳米凝胶的放射性同位素纳米载体提供了概念验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b581/8400054/a53ff6740ba4/pharmaceutics-13-01240-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b581/8400054/83655a1ec16b/pharmaceutics-13-01240-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b581/8400054/3e8234ee95ff/pharmaceutics-13-01240-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b581/8400054/6f4cd3a78b8f/pharmaceutics-13-01240-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b581/8400054/f134d91f90d1/pharmaceutics-13-01240-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b581/8400054/f611d0f56293/pharmaceutics-13-01240-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b581/8400054/a214891c7ffd/pharmaceutics-13-01240-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b581/8400054/c00c3cbbe1e4/pharmaceutics-13-01240-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b581/8400054/b4ed06a48c3f/pharmaceutics-13-01240-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b581/8400054/b97a25f00a29/pharmaceutics-13-01240-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b581/8400054/a53ff6740ba4/pharmaceutics-13-01240-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b581/8400054/83655a1ec16b/pharmaceutics-13-01240-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b581/8400054/3e8234ee95ff/pharmaceutics-13-01240-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b581/8400054/6f4cd3a78b8f/pharmaceutics-13-01240-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b581/8400054/f134d91f90d1/pharmaceutics-13-01240-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b581/8400054/f611d0f56293/pharmaceutics-13-01240-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b581/8400054/a214891c7ffd/pharmaceutics-13-01240-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b581/8400054/c00c3cbbe1e4/pharmaceutics-13-01240-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b581/8400054/b4ed06a48c3f/pharmaceutics-13-01240-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b581/8400054/b97a25f00a29/pharmaceutics-13-01240-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b581/8400054/a53ff6740ba4/pharmaceutics-13-01240-g009.jpg

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