Mimetic sea cucumber-shaped nanoscale metal-organic frameworks composite for enhanced photodynamic therapy

Abstract Therapeutic resistance caused by hypoxia tumor microenvironment (TME) is one of the main challenges for the development of nanoscale delivery systems, particular for the photodynamic agents. In this work, porphyrin-based metal-organic frameworks composite ACF@PCN-222@MnO2-PEG (APM) with the mimetic sea cucumber morphology was post-synthesized for using in photodynamic therapy (PDT) against hypoxia. Besides the good colloidal stability, as-synthesized APM nanoparticles also exhibited the well biocompatibility and H2O2-triggered drug releasing. After being reacted with endogenous H2O2, the amorphous MnO2 layer on the APM outersurface could quickly decompose to produce abundant oxygen, self-compensating for the consumption of photodynamic process. Meanwhile, the highly loaded hypoxia inhibitors acriflavine (ACF) of 18.7 wt% in APM was released to down-regulate the expression level of hypoxia-inducible factors (HIF). Combining with the self-generating oxygen and ACF inhibitors, the tumor hypoxia could be greatly relieved and the better tumor suppression effect by PDT have been demonstrated in vivo. This self-suppling oxygen nanosystem triggered by endogenous tumor markers proves a feasible way for remodeling the hypoxia TME and to achieve better therapeutic performances.