期刊
BIOMATERIALS
卷 278, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2021.121139
关键词
Self-assembly nanocluster; Peptide drug conjugate; Cell membrane penetration; Targeted therapy
资金
- National Natural Science Foundation of China [51725302, 52003270]
PDC drugs offer advantages of improved drug targetability and reduced adverse effects compared to traditional chemotherapy, but their poor permeability to tumor cells needs to be addressed. The designed PDC drug molecule forms nanoclusters upon binding cellular receptor, enhancing treatment efficacy. This strategy leverages assembly principles to promote peptide penetration into cells and increase intracellular drug bioavailability.
Peptide drug conjugate (PDC) has emerged as one of the new generations of targeted therapeutics for cancer, which owns the advantages of improved drug targetability and reduced adverse effects compared with traditional chemotherapy. However, the poor permeability of PDC drugs regarding tumor cells is an urgent problem to be solved. Herein, we design a PDC drug molecule, which is composed of three modules: targeting motif (RGD target), assembly motif (GNNNQNY) and cytotoxic payload (CPT molecule). This PDC in situ forms nanoclusters upon binding cellular receptor, resulting in improved PDC cell-entry efficiency and treatment efficacy. In addition, the PDC shows increased therapeutic efficacy and raises the maximum tolerance dose of the drug in breast and bladder xenografted mice models. This strategy leverages the assembly principle to promote penetration of peptide molecules into cells and increase intracellular drug bioavailability, which is of great significance for the development of PDC drugs in the future.
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