Controlled delivery of a protein tyrosine phosphatase inhibitor, SHP099, using cyclodextrin-mediated host-guest interactions in polyelectrolyte multilayer films for cancer therapy.
Controlled delivery of a protein tyrosine phosphatase inhibitor, SHP099, using cyclodextrin-mediated host-guest interactions in polyelectrolyte multilayer films for cancer therapy.
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含Src同源2结构域的蛋白酪氨酸磷酸酶-2（SHP 2）是调节肿瘤生长信号传导途径中的关键酶，并且最近作为有前途的抗癌药物靶点而引起兴趣。许多SHP 2抑制剂目前正在开发中，包括SHP 099，其在低浓度下在体内显示出有效的抗癌活性。在这项工作中，我们开发了用于局部递送SHP 099的多层涂层，以改善目前的癌症治疗。采用层层自组装法制备了壳聚糖-聚羧甲基-β-环糊精（PβCD）复合膜，并将其用于SHP 099的缓释。SHP 099通过与PβCD的主客体相互作用成功地负载到多层膜中。核磁共振光谱通过鉴定特定末端SHP 099质子与CD质子的相互作用证实了这种超分子组装的发生。在96小时内检测到组装膜中的SHP 099释放，并发现其在体外抑制人乳腺癌细胞的集落形成。这些多层膜有可能用于一系列抗癌应用，并克服全身化疗给药的常见并发症，同时最大限度地提高SHP 099的疗效。高效抗癌药物SHP 099在超分子复合成多功能多层膜后的控制递送。
The Src homology 2 domain containing protein tyrosine phosphatase-2 (SHP2) is a key enzyme in pathways regulating tumor growth signaling, and recently gained interest as a promising anticancer drug target. Many SHP2 inhibitors are currently under development, including SHP099, which has shown potent anticancer activity at low concentrations in vivo. In this work, we developed multilayer coatings for localized delivery of SHP099 to improve upon current cancer therapies. Layer-by-layer self-assembly was used to develop films composed of chitosan and poly-carboxymethyl-β-cyclodextrin (PβCD) for the delivery of SHP099. SHP099 was successfully loaded into multilayer films via host–guest interactions with PβCD. Nuclear magnetic resonance spectroscopy confirmed the occurrence of this supramolecular assembly by identifying the interaction of specific terminal SHP099 protons with the protons of the CD. SHP099 release from assembled films was detected over 96 hours, and was found to inhibit colony formation of human breast adenocarcinoma cells in vitro. These multilayer films have the potential to be used in a range of anticancer applications and overcome common complications of systemic chemotherapeutic administration, while maximizing SHP099 efficacy. Controlled delivery of a potent anticancer drug, SHP099, after supramolecular complexation into a versatile multilayer film.
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影响因子：
14
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影响因子：
7.3
作者：
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LVOV, Y;DECHER, G;MOHWALD, H
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MOHWALD, H
影响因子：
9.5
作者：
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通讯作者：
Lyskawa, Joel
影响因子：
5.5
作者：
Dubas, ST;Schlenoff, JB
通讯作者：
Schlenoff, JB