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Acid-triggered synergistic chemo-photodynamic therapy systems based on metal-coordinated supramolecular interaction.

To enhance anticancer efficacy and decrease side effects, the synergistic multi-agent therapy has now increasingly gotten great attention. Herein, the flexible polycaprolactone had been modified by histidine and formed assembles with PEGylated metallo-porphyrin via metal-coordinated supramolecular interaction. This supramolecular assembles showed excellent acid sensitivity. At neutral environment, the hydrophobic anticancer drug could be effectively co-encapsulated with photosensitizer Fe-TPP to improve the water solubility. While at the intracellular microenvironment, the changed acid environment would trigger the drug and Fe-TPP release due to the reduction of metal-coordinated interaction between histidine and metallo-porphyrin leading to the disintegration of assembles. The in vivo anticancer experiments toward HeLa and MCF-7 cells disclosed that this co-delivery system of anticancer drug and photosensitizer showed enhanced anticancer efficacy, implying that the synergistic chemo-photodynamic therapy could improve cellular proliferation inhibition. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2955-2962, 2018.