A novel supramolecular dendrimeric nanosystem carrying the anticancer drug doxorubicin was developed in this study. We demonstrated this nanosystem markedly overcoming the heterogeneity of drug response and resistance of primary cultured tumor cells derived from 35 PDAC patients. This simple and convenient dendrimer nanodrug holds great promise as a potential candidate to treat the deadly PDAC.
Abstract:
Biological applications of nanomaterials as delivery carriers have been embedded in traditional biomedical research for decades. Despite lagging behind, recent significant breakthroughs in the use of nanocarriers as tools for plant biotechnology have created great interest. In this Perspective, we review the outstanding recenPancreatic ductal adenocarcinoma (PDAC) is a deadly cancer with no efficacious treatment. The application of nanomedicine is expected to bring new hope to PDAC treatment. In this study, we report a novel supramolecular dendrimeric nanosystem carrying the anticancer drug doxorubicin, which demonstrated potent anticancer activity, markedly overcoming the heterogeneity of drug response and resistance of primary cultured tumor cells derived from PDAC patients. This dendrimer nanodrug was constructed with a fluorinated amphiphilic dendrimer, which self-assembled into micelles nanostructure and encapsulated doxorubicin with high loading. Because of the fine nanosize, stable formulation and acid-promoted drug release, this dendrimeric nanosystem effectively accumulated in tumor, with deep penetration in tumor tissue and rapid drug uptake/release profile in cells, ultimately resulting in potent anticancer activity and complete suppression of tumor growth in patient-derived xenografts. Most importantly, this dendrimer nanodrug generated uniform and effective response when treating 35 primary pancreatic cancer cell lines issued from patient samples as a robust platform for preclinical drug efficacy testing. In addition, this dendrimer nanodrug formulation was devoid of adverse effects and showed excellent tolerability. Given all these uniquely advantageous features, this simple and convenient dendrimer nanodrug holds great promise as a potential candidate to treat the deadly PDAC.
Author list:
Juan Liu, Chao Chen, Tuo Wei, Odile Gayet, Céline Loncle, Laurence Borge, Nelson Dusetti, Xiaowei Ma, Domenico Marson, Erik Laurini, Sabrina Pricl, Zhongwei Gu, Juan Iovanna, Ling Peng*, Xing-Jie Liang*
How to cite:
J. Liu, C. Chen, T. Wei, O. Gayet, C. Loncle, L. Borge, N. Dusetti, X. Ma, D. Marson, E. Laurini, S. Pricl, Z. Gu, J. Iovanna, L. Peng, X.-J. Liang, Exploration 2021, 1, 21-34.
https://doi.org/10.1002/EXP.20210003