Multifunctional nano-MOFs based on tumor microenvironment modulation for detecting singlet oxygen and enhancing photodynamic therapy

Abstract

Photodynamic therapy (PDT) has been extensively used in tumor therapy due to its excellent selectivity, minimal toxicity, and tolerability. However, several indicators in the tumor microenvironment (TME) are abnormal. The therapeutic impact of PDT is compromised due to ¹O₂ depletion caused by the overexpression of glutathione (GSH). Additionally, the concentration of ¹O₂ during the treatment is still undefined. Insufficient or excessive therapeutic effects could occur, making it impossible to achieve precise treatment. Accordingly, we designed a multifunctional nanosystem (DPA-MOF@MnO₂-Ce6@PEG) that integrates a TME regulatory unit, ¹O₂ generation unit, and ¹O₂ detection probe to address the above problems. Upon laser radiation, the modification of MnO₂ altered the amount of GSH in the TME, which reduced the depletion of ¹O₂ mediated by the photosensitizer Ce6, with the aim of augmenting the effectiveness of PDT. Concurrently, DPA-MOF captured the generated ¹O₂, and the fluorescence quenching of the probe provided feedback on the ¹O₂ level during PDT. A coating of polyethylene glycol (PEG) was used to enhance the dispersity of the nanoparticles and prevent the leakage of the photosensitizer. As expected, the designed multifunctional nanoparticles exhibited good detection capability towards ¹O₂, GSH depletion capacity, and potent antitumor activity in 4T1 and MCF-7 tumor cells. This work provided an insight into the precise treatment of PDT and a solution for the depletion of over-expressed GSH in TME to enhance PDT.