Self-Targeted, Shape-Assisted, and Controlled-Release Self-Delivery Nanodrug for Synergistic Targeting/Anticancer Effect of Cytoplasm and Nucleus of Cancer Cells.

Abstract

We constructed 10-hydroxycamptothecin (CPT) "nanodrugs" with functionalization of lipid-PEG-methotrexate (MTX) to prepare high-drug-loaded, and sustained/controlled-release MTX-PEG-CPT nanorods (NRs), in which MTX drug itself can serve as a specific "targeting ligand". The self-targeted nanodrug can codeliver both CPT and MTX drugs with distinct anticancer mechanisms. Furthermore, MTX-PEG-CPT NRs significantly reduced burst release, improved blood circulation and tumor accumulation, enhanced cellular uptake, and synergistically increased anticancer effect against tumor cells compared with MTX-PEG-CPT nanospheres (NSs) and either both free drugs or individual free drug. Therefore, the synergistic targeting/therapeuticy nano-multi-drug codelivery assisted by shape design may advantageously offer a promising new strategy for nanomedicine.

• Authors: Yang Li, Jinyan Lin, Yu Huang, Yanxiu Li, Xiangrui Yang, Hongjie Wu, Shichao Wu, Liya Xie, Lizong Dai, Zhenqing Hou
• Journal: ACS applied materials & interfaces (ACS Appl Mater Interfaces) Vol. 7 Issue 46 Pg. 25553-9 (Nov 25 2015) ISSN: 1944-8252 [Electronic] United States
• PMID: 26529185 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Delayed-Action Preparations
• 10-hydroxycamptothecin
• Camptothecin
• Methotrexate

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Camptothecin (analogs & derivatives, pharmacology)
• Cell Line, Tumor
• Cell Nucleus (drug effects, metabolism)
• Cell Survival (drug effects)
• Delayed-Action Preparations
• Drug Synergism
• Endocytosis (drug effects)
• Fluorescence
• Methotrexate (pharmacology)
• Mice, Inbred BALB C
• Mice, Nude
• Nanospheres (chemistry, ultrastructure)
• Nanotubes (chemistry, ultrastructure)
• Particle Size
• Rats, Sprague-Dawley