期刊
ADVANCED FUNCTIONAL MATERIALS
卷 31, 期 29, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.202102004
关键词
cascade drug release; dual‐ tumor targeting; hydrophilic; hydrophobic drugs; protein cage nanocarrier; synergistic chemotherapy
类别
资金
- Strategic Priority Research Program of CAS [XDB29040101]
- National Natural Science Foundation of China [31900981]
- CAS Interdisciplinary Innovation Team [JCTD-2020-08]
- Chinese Academy of Sciences [YJKYYQ20180048]
- Key Research Program of Frontier Sciences, CAS [QYZDY-SSW-SMC013]
- National Key Research and Development Program of China [2017YFA0205501]
- Youth Innovation Promotion Association of Chinese Academy of Sciences [2019093]
- China Postdoctoral Science Foundation [2019M660826]
The Am-PNCage is a novel protein nanocarrier with dual-targeting properties, allowing for effective drug loading and promoting drug penetration and accumulation in tumors in vivo.
A biocompatible and modifiable protein nanocarrier is a promising candidate for tumor targeted drug delivery. However, it is challenging to effectively load hydrophobic drugs, not to mention to upload both hydrophilic and hydrophobic drugs on one protein nanocarrier. Here, an amphiphilic multi-drug loading protein nanocage (Am-PNCage) is presented which is generated by replacing the fifth helix of human H-ferritin (HFn) subunit with a functional motif composed of hydrophobic-hydrophilic-RGD peptides. The Am-PNCage possesses a dual targeting property resulting from the intrinsic CD71 targeting ability of HFn and the integrin alpha v beta 3 targeting ability of displayed RGD peptides. Through the hydrophilic drug entry channel in the protein nanocage and hydrophobic peptides displayed on the outer surface, amphiphilic epirubicin (132)/camptothecin (50) are stereoscopically loaded into the inner cavity/outer protein shell, respectively, for one Am-PNCage, exhibiting cascade drug release pattern. The dual-targeted Am-PNCage promotes the loaded drugs penetrating various 3D tumor models in vitro, as well as traversing the brain blood barrier and accumulating in brain tumors in vivo. Moreover, the drug loaded Am-PNCage shows reduced side effects and significantly enhances synergistic efficacy against brain tumor, metastatic liver cancers, and drug resistant breast tumor. Thus, the Am-PNCage represents a novel promising protein nanocarrier for targeted combination chemotherapy.
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