Redox-Responsive Tetraphenylethylene-Buried Cross-Linked Vesicles for Enhanced Drug Loading and Efficient Drug Delivery Monitoring
Liposomes have been applied extensively as nanocarriers in clinic, e.g. to deliver anticancer drugs, due to its biocompatibility and cavity structure inside. However, the low drug-loading capacity (< 10%) and uncontrolled release significantly reduced its efficiency in cancer treatment. In order to improve the drug loading capacity and monitor real-time release of drugs in cells, stimuli-responsive vesicles are urgently needed to be developed. Here, we present various amphiphilic tetraphenylethylene (TPE)-containing compounds that are designed to self-assemble into liposome-like vesicles, which can load both hydrophilic and hydrophobic drugs. The highest drug loading content for doxorubicin (DOX) can be up to 26% for the vesicles (diameter 105 nm) by encapsulating hydrophilic DOX in the interior water pool and hydrophobic DOX via π-π stacking interaction between DOX and TPE moiety. The stable vesicles can quickly respond to over-expressed glutathione in tumor microenvironment to release loaded DOX for cancer therapy. The vesicles modified by active targeting groups show more efficient tumor therapeutic treatment compared to unmodified ones and free DOX, as shown by both in vitro and in vivo. Simultaneously, we observed spatiotemporally the sub-cellular location of the delivery system and release process of DOX. Our work provides a novel nano-engineering technology to integrate the desired properties for anticancer theranostics, including high loading capacity, stability, stimuli-response to cancer environment, drug delivery monitoring, active targeting and compression of tumor growth. The novel vesicles have great potential to be applied as multifunctional drug delivery systems for cancer therapy.