Theranostic supramolecular polymers formed by self-assembly of a metal-chelating prodrug
2020
Therapeutic constructs with imaging modalities hold great promise for improving the treatment efficacy for cancer and many other diseases. We report here on the design and synthesis of a self-assembling prodrug (SAPD) by direct linkage of camptothecin (CPT), an anticancer drug, to a metal-chelating agent, DOTA. We found that under the physiological condition the DOTA-conjugated CPT prodrug can self-assemble into tubular supramolecular polymers (SPs) of several micrometers in length. Our studies also suggest that the resultant assemblies were stable in biological environments and exhibited a fast drug release rate in the presence of intracellular glutathione. Furthermore, the SAPD exerted remarkable in vitro efficacy against various cancer cell lines and can effectively inhibit the growth of tumor spheroids. We believe the design and optimization of self-assembling theranostic conjugates could provide a robust yet simple platform for the development of new imaging-guided drug delivery systems.
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