Self-Assembled Lenalidomide/AIE Prodrug Nanobomb for Tumor Imaging and Cancer Therapy
Zhijian Mai (South China Normal University)
Nengjie Cao (South China Normal University)
Erzhuo Cheng (The First Affiliated Hospital of Guangzhou Medical University)
Zhiwen Zeng (South China Normal University)
Yancong Feng (South China Normal University)
Yao Wang (South China Normal University)
Paddy J. French (TU Delft - Bio-Electronics)
Yi Kuen Lee (The Hong Kong University of Science and Technology)
Haihong Yang (The First Affiliated Hospital of Guangzhou Medical University)
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Abstract
To develop multifunctional small-molecule prodrugs is highly desirable for cancer treatment but remains challenging in intrinsic traceability. As an acid-cleavable linkage, a Schiff bases benefiting from its distinctive fluorescence quenching ability was selected to prepare a small-molecule prodrug with cancer-targeted and self-indicating. In this study, we designed and developed a multifunctional self-assembled nanobomb of amphiphilic TPE-Lenalidomide prodrug, which comprises a hydrophobic aggregation-induced emission (AIE) probe 4-(1,2,2-triphenylvinyl)benzaldehyde (TPE-CHO) and a hydrophilic anticancer drug Lenalidomide via a Schiff base linkage. We investigated the synergistic effect of d-PET and C═N isomerization which would keep the fluorescence of TPE-Lenalidomide in the “always off” state by density functional theory (DFT) calculation. Once reaching the pathological site, such a vesicular nanobomb of TPE-Lenalidomide will be acidolyzed to release the AIE probe and Lenalidomide molecules simultaneously, consequently realizing high-efficiency effects of tumor imaging and cancer therapy (cell viability: normal cell L929, ∼79.49%; cancer cell 4T1, ∼27.08%; p = 0.000118). This work may pave an avenue to prepare small-molecule prodrugs for tumor-targeted diagnosis and cancer therapy.