Self-Assembled Lenalidomide/AIE Prodrug Nanobomb for Tumor Imaging and Cancer Therapy

Zhijian Mai; Nengjie Cao; Erzhuo Cheng; Zhiwen Zeng; Yancong Feng; Yao Wang; Paddy J. French; Yi Kuen Lee; Haihong Yang; null More Authors

doi:10.1021/acsanm.3c03611

Self-Assembled Lenalidomide/AIE Prodrug Nanobomb for Tumor Imaging and Cancer Therapy

Zhijian Mai, Nengjie Cao, Erzhuo Cheng, Zhiwen Zeng, Yancong Feng, Yao Wang^*, Paddy J. French, Yi Kuen Lee, Haihong Yang, More Authors

^*Corresponding author for this work

Bio-Electronics

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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.

Original language	English
Pages (from-to)	19807-19817
Number of pages	11
Journal	ACS Applied Nano Materials
Volume	6
Issue number	21
DOIs	https://doi.org/10.1021/acsanm.3c03611
Publication status	Published - 2023

Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 51973070, 51903062), Science and Technology Program of Guangzhou (No. 2019050001 and 202102020757), Guangdong Basic and Applied Basic Research Foundation (No. 2022A1515010577, 2021A1515012420, 2021A1515010596), Innovative Team Project of Education Bureau of Guangdong Province (2018KCXTD009), Guangdong Science and Technology Project-International Cooperation (2022A0505050069), Startup Foundation from SCNU, Guangdong Provincial Key Laboratory of Optical Information Materials and Technology (No. 2017B030301007), MOE International Laboratory for Optical Information Technologies, the 111 Project, Science and Technology Innovation Strategy Special Foundation of Guangdong (No. pdjh2023b0144). The calculation of this work was performed on Bianshui Riverside Supercomputing Center (BRSC).

Keywords

aggregation-induced emission
Schiff base linkage
self-assembly
small-molecule prodrug
tumor-targeted diagnosis and therapy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/acsanm.3c03611

mai-et-al-2023-self-assembled-lenalidomide-aie-prodrug-nanobomb-for-tumor-imaging-and-cancer-therapyFinal published version, 11.6 MB

Cite this

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title = "Self-Assembled Lenalidomide/AIE Prodrug Nanobomb for Tumor Imaging and Cancer Therapy",

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.",

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AU - Mai, Zhijian

AU - Cao, Nengjie

AU - Cheng, Erzhuo

AU - Zeng, Zhiwen

AU - Feng, Yancong

AU - Wang, Yao

AU - French, Paddy J.

AU - Lee, Yi Kuen

AU - Yang, Haihong

AU - More Authors, null

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AB - 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.

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Self-Assembled Lenalidomide/AIE Prodrug Nanobomb for Tumor Imaging and Cancer Therapy

Abstract

Funding

Keywords

UN SDGs

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