Lysophosphatidic acid responsive photosensitive supramolecular organic frameworks for tumor imaging, drug loading, and photodynamic therapy

Supramolecular organic frameworks have been widely applied for biological detection and drug delivery. In this study, a supramolecular organic framework (SOF) is constructed through the self-assembly of a highly photosensitive triarylphosphine oxide guest molecule, OTPP-6-Methyl, with cucurbit [8] uril (CB [8]). The formation of the SOF gradually enhances the weak fluorescence of OTPP-6-Methyl owing to the restriction of the molecular folding motion. Although the high positive charge of OTPP-6-Methyl facilitates binding to various negatively charged substances, the SOF system only demonstrated an obvious fluorescence response to LPA, a biomarker of ovarian cancer, via the disassembly of SOF and subsequent binding of OTPP-6-Methyl with LPA. The fluorescence changes during the entire process are insufficient to allow the sensitive detection of LPA; thus, we further designed a FRET system by introducing Cy5, which can act as an energy receptor to achieve a ratiometric readout for LPA. The tumor-targeting cRGD group was introduced into the SOF system as part of another guest molecule, OTPP-5-M-1-cRGD, to improve the tumor-targeting ability of the SOF system. The SOF system further improves the photosensitivity of guest molecules, and is therefore used in the in vivo imaging of ovarian cancer subcutaneous tumors and as a DDS for loading DOX for the combined in vivo chemotherapy and photodynamic treatment of tumors.