Department of Chemistry, Shands Cancer Center, UF Genetics Institute, University of Florida, Gainesville, Florida 32611-7200, USA.
Chem Asian J. 2012 Jun;7(7):1630-6. doi: 10.1002/asia.201101060. Epub 2012 Apr 11.
Monovalent aptamers can deliver drugs to target cells by specific recognition. However, different cancer subtypes are distinguished by heterogeneous biomarkers and one single aptamer is unable to recognize all clinical samples from different patients with even the same type of cancers. To address heterogeneity among cancer subtypes for targeted drug delivery, as a model, we developed a drug carrier with a broader recognition range of cancer subtypes. This carrier, sgc8c-sgd5a (SD), was self-assembled from two modified monovalent aptamers. It showed bispecific recognition abilities to target cells in cell mixtures; thus broadening the recognition capabilities of its parent aptamers. The self-assembly of SD simultaneously formed multiple drug loading sites for the anticancer drug doxorubicin (Dox). The Dox-loaded SD (SD-Dox) also showed bispecific abilities for target cell binding and drug delivery. Most importantly, SD-Dox induced bispecific cytotoxicity in target cells in cell mixtures. Therefore, by broadening the otherwise limited recognition capabilities of monovalent aptamers, bispecific aptamer-based drug carriers would facilitate aptamer applications for clinically heterogeneous cancer subtypes that respond to the same cancer therapy.
单价适体可以通过特异性识别将药物递送到靶细胞。然而，不同的癌症亚型通过异质生物标志物区分，并且单一适体无法识别来自不同患者的所有临床样本，即使是相同类型的癌症。为了解决癌症亚型之间的异质性以进行靶向药物递送，我们以一种模型开发了一种具有更广泛的癌症亚型识别范围的药物载体。该载体 sgc8c-sgd5a（SD）由两个修饰的单价适体自组装而成。它显示出对细胞混合物中靶细胞的双特异性识别能力；从而拓宽了其亲本适体的识别能力。SD 的自组装同时为抗癌药物阿霉素（Dox）形成了多个药物装载点。载有 Dox 的 SD（SD-Dox）也显示出对靶细胞结合和药物递送的双特异性能力。最重要的是，SD-Dox 在细胞混合物中的靶细胞中诱导了双特异性细胞毒性。因此，通过拓宽单价适体原本有限的识别能力，基于双特异性适体的药物载体将促进适体在对相同癌症治疗有反应的临床异质癌症亚型中的应用。
