期刊
ACTA BIOMATERIALIA
卷 164, 期 -, 页码 407-421出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2023.04.026
关键词
Nanomedicine; Supramolecular assembly; Hydrophilic drug delivery; Photodynamic therapy; Chemotherapy
We propose a supramolecular assembly strategy to enhance drug loading, tumor targeting, and delivery simplicity for hydrophilic drugs. By co-assembling with other drugs, we validate the effectiveness of this strategy and demonstrate its application in anti-tumor activities.
To improve the drug loading, tumor targeting, and delivery simplicity of hydrophilic drugs, we propose a supramolecular assembly strategy that potentially benefits a wide range of hydrophilic drug delivery. Firstly, we choose a hydrophilic drug (tirapazamine) as a model drug to directly co-assemble with chlorin e6 (Ce6) at different molar ratios, and systematically evaluate the resultant Ce6-tirapazamine nanoparti-cles (CT NPs) in aspects of size distribution, polydispersity, morphology, optical properties and molecular dynamics simulation. Based on the assembling facts between Ce6 and tirapazamine, we summarize a plausible rule of the supramolecular assembly for hydrophilic drugs. To validate our findings, more drugs with increasing hydrophilicity, such as temozolomide, gemcitabine hydrochloride and 5-azacytidine, suc-cessfully co-assemble with Ce6 into nanostructures by following similar assembling behaviors, demon-strating that our assembling rule may guide a wide range of hydrophilic drug delivery. Next, the combina-tion of Ce6 and tirapazamine was chosen as the representative to investigate the anti-tumor activities of the supramolecular assemblies. CT NPs showed synergistic anti-tumor efficacy, increased tumor accumu-lation and significant tumor progression and metastasis inhibition in tumor-bearing mice. We anticipate that the supramolecular assembly mechanism will provide broad guidance for developing easy-to-make but functional nanomedicines.Statement of Significance Although thousands of nanomedicines have been developed, only a few have been approved for clinical use. The manufacturing complexity significantly hinders the bench-to-bed translation of nanomedicines. Hence, we need to rethink how to conduct research on translational nanomedicines by avoiding more and more complex chemistry and complicated nanostructures. Here, we summarize a plausible rule according to multiple supramolecular assembly pairs and propose a supramolecular assembly strategy that can im-prove the drug loading, tumor targeting, and manufacturing simplicity of nanomedicine for hydrophilic drugs. The supramolecular assembly strategy would guide a broader range of drug delivery to provide a new paradigm for developing easy-to-make but multifunctional nanoformulations for synergistic cancer treatment.& COPY; 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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