In vivo high-efficiency targeted photodynamic therapy of ultra-small Fe3O4@polymer-NPO/PEG-Glc@Ce6 nanoprobes based on small size effect

Effectively prolonging the residence time of nanoprobes in the tumor region and reducing the accumulation of nanoprobes in the vital organs (for example, lung, liver and spleen) is crucial for high-efficiency photodynamic therapy (PDT) of cancer. Herein, we systematically report an ultra-small and highly stable nanoplatform with diameters of 4, 8 and 13 nm that exhibited excellent photodynamic therapeutic efficacy using Fe₃O₄@polymer-NPO/PEG-Glc@Ce6 nanoprobes. Based on the small size effect, the nanoprobes displayed lower cytotoxicity and excellent biocompatibility. Owing to the synergistic virtues of markedly active targeting and intrinsic small size effect, the Fe₃O₄@P-NPO/PEG-Glc@Ce6 nanoprobes can effectively prolong their residence time in the tumor region and reduce accumulation in the normal organs. Benefitting from the small size effect, the synthesized Fe₃O₄@P-NPO/PEG-Glc@Ce6 nanoprobes exhibited excellent tumor-targeting capability and photodynamic therapeutic efficacy by inhibiting the growth of tumors in mice under visible red light irradiation with a relatively lower power. The successful application of the small size effect in Fe₃O₄@P-NPO/PEG-Glc@Ce6 nanoprobes to significantly improve the PDT efficiency in our strategy suggests new building blocks for PDT of tumors and paves a new way for clinical therapies and translation in the near future.