Robust Chemical Strategy for Stably Labeling Polyester-Based Nanoparticles with BODIPY Fluorophores.
Robust Chemical Strategy for Stably Labeling Polyester-Based Nanoparticles with BODIPY Fluorophores.
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用BODIPY荧光团稳定标记聚酯基纳米颗粒的稳健化学策略。
DOI：
10.1021/acsapm.1c01601
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发表时间：
2022-02-11
影响因子：
5
通讯作者：
Chorny, Michael
中科院分区：
文献类型：
--
作者：
Alferiev, Ivan S.;Fishbein, Ilia;Levy, Robert J.;Chorny, Michael
脂肪族聚酯是最广泛用于生产可生物降解的聚合物纳米颗粒的材料之一，目前正在开发作为递送载体和成像剂用于一系列生物医学应用。它们的临床转化需要强大的颗粒标记方法，以可靠地监测这些制剂在复杂生物环境中的命运。在本研究中，一个实用的和通用的合成策略，提供共轭物的聚（D，L-丙交酯）代表这类聚合物与BODIPY荧光团不同的官能团和激发/发射最大值进行了研究，作为一种工具，使可追溯的纳米粒子。聚合物-探针缀合通过以下方式完成：通过马来酰亚胺诱导的和4-（二甲基氨基）吡啶4-甲苯磺酸盐催化的聚合物末端羟基的酯化，直接与羧基官能化荧光团或与胺保护的氨基酸（Boc-甘氨酸或Boc-6-氨基己酸）酯化。在后一种情况下，氨基酸衍生的聚合物前体在除去保护基后与胺反应性BODIPY染料反应。与封装强疏水性BODIPY 505/515（logPo/w = 4.3）的纳米颗粒不同，用其羧基官能化类似物（BODIPY FL）共价标记的纳米颗粒在完美的下沉条件下表现出稳定的颗粒-示踪剂缔合。此外，与包封的染料从颗粒快速分配到细胞膜上但不稳定地被培养的细胞保留相反，共价连接的探针的内化是需要血清存在的不可逆过程，与通过内吞作用的活性纳米颗粒摄取一致。总之，颗粒形成聚合物与BODIPY荧光团的缀合提供了一种有效且可获得的标记策略，用于制备可追踪的基于聚酯的生物可降解纳米颗粒，并有望促进其作为治疗载体和诊断剂的开发和优化。
Aliphatic polyesters are among materials most extensively used for producing biodegradable polymeric nanoparticles currently in development as delivery carriers and imaging agents for a range of biomedical applications. Their clinical translation requires robust particle labeling methodologies that allow reliably monitoring the fate of these formulations in complex biological environments. In the present study, a practical and versatile synthetic strategy providing conjugates of poly(D,L-lactide) representative of this class of polymers with BODIPY fluorophores varying in functional groups and excitation/emission maxima was investigated as a tool for making traceable nanoparticles. Polymer-probe conjugation was accomplished by carbodiimide-induced and 4-(dimethylamino)pyridinium 4-toluenesulfonate-catalyzed esterification of the polymer’s terminal hydroxyl group, either directly with a carboxy-functionalized fluorophore or with amine-protected amino acids (Boc-glycine or Boc-6-aminohexanoic acid). In the latter case, the amino acid-derivatized polymeric precursors were reacted with amine-reactive BODIPY dyes after the removal of the protective group. Unlike nanoparticles encapsulating a strongly hydrophobic BODIPY505/515 (logPo/w = 4.3), nanoparticles labeled covalently with its carboxy-functionalized analogue (BODIPY FL) demonstrated stable particle-tracer association under perfect sink conditions. Furthermore, in contrast to the encapsulated dye rapidly partitioning from particles onto cell membranes but not stably retained by cultured cells, the internalization of the covalently attached probe was an irreversible process requiring the presence of serum, consistent with active nanoparticle uptake by endocytosis. In conclusion, the conjugation of particle-forming polymers with BODIPY fluorophores offers an effective and accessible labeling strategy for making traceable polyester-based biodegradable nanoparticles and is expected to facilitate their development and optimization as therapeutic carriers and diagnostic agents.
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影响因子：
3.7
作者：
Chorny, Michael;Alferiev, Ivan S.;Fishbein, Ilia;Tengood, Jillian E.;Folchman-Wagner, Zoe;Forbes, Scott P.;Levy, Robert J.
通讯作者：
Levy, Robert J.
DOI：
10.1016/j.jconrel.2015.12.025
发表时间：
2016-01-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Adamo RF;Fishbein I;Zhang K;Wen J;Levy RJ;Alferiev IS;Chorny M
通讯作者：
Chorny M
影响因子：
12.4
作者：
Chorny, Michael;Fishbein, Ilia;Levy, Robert J.
通讯作者：
Levy, Robert J.
影响因子：
3.4
作者：
Anh Minh Huynh;Mueller, Andreas;Jung, Gregor
通讯作者：
Jung, Gregor
影响因子：
4.9
作者：
Chorny M;Fishbein I;Alferiev I;Levy RJ
通讯作者：
Levy RJ