Molecular superglue-mediated higher-order assembly of TRAIL variants with superior apoptosis induction and antitumor activity

Yang, Hao; Li, Heng; Yang, Fen; Tao, Ze; Shi, Qiuxiao; She, Tianshan; Feng, Yanru; Zhao, Li; Chen, Jie; Zhong, Yi; Su, Tan; Zeng, Wengjuan; Zhang, Yong; Wang, Shisheng; Li, Lan; Long, Tingting; Liang, De; Cheng, Jun; Zhu, Hong; Lu, Xiaofeng

doi:10.1016/j.biomaterials.2023.121994

Cited by 2 publications

(1 citation statement)

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“…In addition, the conjugation of chemical drugs to ABD‐Tri was also confirmed by measuring the molecular weight of the conjugate by native mass spectrometry (MS) performed on a Waters Synapt G2‐Si Q‐TOF mass spectrometer equipped with an ESI source and ultra‐performance liquid chromatography (Waters , MA) according to previous descriptions. [ 43 ] The conjugate of ABD‐Tri and vcMMAE was designated ABD‐Tri‐MMAE. Accordingly, the conjugate of ABD‐Tri and CL2‐SN38 was designated ABD‐Tri‐SN38.…”

Section: Methodsmentioning

confidence: 99%

A Versatile Platform to Generate Prodrugs with Rapid and Precise Albumin Hitchhiking and High Cargo Loading for Tumor‐Targeted Chemotherapy

Li,

Xing,

Chen

et al. 2023

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Due to its tumor homing and long serum half‐life, albumin is an ideal drug carrier for chemotherapy. For endogenous albumin hitchhiking with high cargo loading, a trimeric albumin‐binding domain (ABD), i.e., ABD‐Tri is designed by fusing an ABD with high specificity and affinity for albumin to a self‐trimerizing domain (Tri) with an additional cysteine residue. ABD‐Tri is highly (40 mg L−1) expressed as soluble and trimeric proteins in Escherichia coli (E. coli). Once mixed together, ABD‐Tri rapidly and specifically forms a stable complex with albumin under physiological conditions without obviously changing its receptor‐ and cell‐binding and tumor‐homing properties. Maleimide‐modified prodrugs are highly effectively conjugated to ABD‐Tri to produce homogenous ABD‐Tri‐prodrugs with triple cargo loading under physiological conditions by thiol–maleimide click chemistry. Unlike the maleimide moiety, which can only mediate time‐ and concentration‐dependent albumin binding, ABD‐Tri mediated fast (within several minutes) albumin binding of drugs even at extremely low concentrations (µg mL−1). Compared to maleimide‐modified prodrugs, ABD‐Tri‐prodrugs exhibit better tumor homing and greater in vivo antitumor effect, indicating that conjugation of chemical drug to ABD‐Tri outperforms maleimide modification for endogenous albumin hitchhiking. The results demonstrate that ABD‐Tri may serve as a novel platform to produce albumin‐binding prodrugs with high cargo‐loading capacity for tumor‐targeted chemotherapy.

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Section: Methodsmentioning

confidence: 99%