Controlled Delivery of BET-PROTACs: In Vitro Evaluation of MZ1-Loaded Polymeric Antibody Conjugated Nanoparticles in Breast Cancer.
Controlled Delivery of BET-PROTACs: In Vitro Evaluation of MZ1-Loaded Polymeric Antibody Conjugated Nanoparticles in Breast Cancer.
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BET-Protacs的受控递送：在乳腺癌中对MZ1负载的聚合物抗体共轭纳米颗粒的体外评估。
DOI：
10.3390/pharmaceutics12100986
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发表时间：
2020-10-19
期刊：
影响因子：
5.4
通讯作者：
Ocaña A
中科院分区：
文献类型：
--
作者：
Cimas FJ;Niza E;Juan A;Noblejas-López MDM;Bravo I;Lara-Sanchez A;Alonso-Moreno C;Ocaña A
溴和末端外结构域（BET）催化剂-蛋白水解Targeting嵌合体（BETi-PROTAC）是一种新的化合物家族，其通过标记至BET抑制剂溴结构域蛋白BRD 2和BRD的泛素化来诱导蛋白酶体降解。BET-PROTAC通过其与抗体（如曲妥珠单抗）的载体化的包封和控制释放可以促进其药代动力学和功效特征。尚未设计和评价使用PROTAC的抗体缀合纳米颗粒（ACNP）。在这种先驱方法中，商业MZ 1 PROTAC被封装到FDA批准的聚合物纳米颗粒中。将纳米颗粒与曲妥珠单抗缀合，以引导MZ 1递送至过表达HER 2的乳腺肿瘤细胞。这些ACNP的特征在于通过大小，多分散指数，和Z-电位。纳米颗粒的形态，沿着稳定性和释放研究，完成了表征。MZ 1负载的ACNP显示出显著的细胞毒性作用，维持其作用机制并改善其治疗特性。
Bromo and extraterminal domain (BET) inhibitors-PROteolysis TArgeting Chimera (BETi-PROTAC) is a new family of compounds that induce proteasomal degradation through the ubiquitination of the tagged to BET inhibitors Bromodomain proteins, BRD2 and BRD. The encapsulation and controlled release of BET-PROTACs through their vectorization with antibodies, like trastuzumab, could facilitate their pharmacokinetic and efficacy profile. Antibody conjugated nanoparticles (ACNPs) using PROTACs have not been designed and evaluated. In this pioneer approach, the commercial MZ1 PROTAC was encapsulated into the FDA-approved polymeric nanoparticles. The nanoparticles were conjugated with trastuzumab to guide the delivery of MZ1 to breast tumoral cells that overexpress HER2. These ACNPs were characterized by means of size, polydispersity index, and Z-potential. Morphology of the nanoparticles, along with stability and release studies, completed the characterization. MZ1-loaded ACNPs showed a significant cytotoxic effect maintaining its mechanism of action and improving its therapeutic properties.
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影响因子：
62.1
作者：
Kamaly N;Yameen B;Wu J;Farokhzad OC
通讯作者：
Farokhzad OC
影响因子：
8.8
作者：
Pawar, Aishwarya;Gollavilli, Paradesi Naidu;Asangani, Irfan A.
通讯作者：
Asangani, Irfan A.
影响因子：
5.3
作者：
Niza, Enrique;del Mar Noblejas-Lopez, Maria;Alonso-Moreno, Carlos
通讯作者：
Alonso-Moreno, Carlos
影响因子：
2.9
作者：
Sun, Xiuyun;Rao, Yu
通讯作者：
Rao, Yu
发现具有细胞效力的新型小分子诱导溴结构域和末端外 (BET) 溴结构域蛋白 BRD4 和 BRD2 的选择性降解
影响因子：
3.5
作者：
Jiang, Fei;Wei, Qingyun;Chen, Yadong
通讯作者：
Chen, Yadong