Rationally designed bioconjugates of photosensitizers have been shown to enhance the photochemical effect of photodynamic therapy (PDT) via altering the sub-cellular localization of the photosensitizers or modulating the function of ATP-binding cassette (ABC) transporters. P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) are the two key members that contribute to chemoresistance and PDT resistance in cancer. Here, we introduce a porphyrin-based phospholipid conjugation strategy to circumvent and inhibit the efflux function of ABC drug transporters. Our results show the porphyrin-phospholipid conjugate enhances the photosensitizer accumulation and modulates the enzymatic activity and protein integrity of ABCB1 and ABCG2.
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