期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：48
页码：13720-13725
DOI：10.1073/pnas.1616836113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceBecause of severe side effects, poor specificity, and lack of any ability to track the process of translocation, clinic applications of platinum anticancer drugs are limited. New motifs that combine a targeting ability, diagnostic capabilities, and therapeutic functions are urgently needed. Herein, we use a highly emissive metallacage as a component of theranostic supramolecular nanoparticles. In vitro and in vivo investigations demonstrate the metallacage-loaded nanoparticles (MNPs) are more active and show low systemic activity while also possessing emissive properties that allow for fluorescence imaging. This metallacage provides an excellent nanoplatform on which to develop theranostic anticancer agents, providing a blueprint for the next generation of nanomedicines and the development of noble metal-based-targeted drug delivery systems. A theranostic agent combines diagnostic reporter with therapeutic activity in a single entity, an approach that seeks to increase the efficacy of cancer treatment. Herein, we describe the synthesis of a highly emissive tetraphenylethene-based metallacage using multicomponent coordination-driven self-assembly that exhibits a coordination-triggered aggregation-induced emission (AIE) enhancement. The formation of metallacage-loaded nanoparticles (MNPs) occurs when the assembly is treated with two variants of a 1,2-distearoyl-phosphatidylethanolamine (DSPE)/polyethylene glycol (PEG) conjugate, mPEG-DSPE, and biotin-PEG-DSPE. This combination endows the resultant MNPs with excellent stability and targeting ability, specifically enabling selective delivery of the metallacages to cancer cells that overexpress biotin receptors via receptor-mediated endocytosis. Although the mechanism of activity is based on existing Pt(II) anticancer drugs such as oxaliplatin, carboplatin, and cisplatin, in vitro and in vivo studies indicate that the MNPs are more active and show low systemic activity while also possessing emissive properties that allow for fluorescence-based imaging. This pioneering example of a metallacage that combines biologically active components with AIE imaging establishes supramolecular coordination complexes imbedded within nanoparticles as a promising potential theranostic platform for cancer treatment.
