Biodegradable Reduce Expenditure Bioreactor For Augmented Sonodynamic Therapy Via Regulating Tumor Hypoxia And Inducing Pro-Death Autophagy

Abstract

Backgrounds: Sonodynamic therapy (SDT) as an emerging reactive oxygen species (ROS)-mediated antitumor means is still hampered by the rapid depletion of oxygen, as well as hypoxic tumor microenvironment. Instead of the currently coping strategies through amplifying endogenous O2 level, herein, a biodegradable O2 economizer is described as a reduce expenditure bioreactor for augmenting SDT efficacy. Results: We have successfully fabricated the O2 economizer (HMME@HMONs-3BP-PEG, HHBP) by the conjugation of respiration inhibitor 3-bromopyruvate (3BP) with hollow mesoporous organosilica nanoparticles (HMONs), followed by the loading of organic sonosensitizers (HMME) and further surface modification of poly(ethylene glycol) (PEG). The engineered HHBP features controllable pH/GSH/US-sensitive drug release. The exposed 3BP could effectively inhibit cell respiration for restraining the oxygen consumption, which could alleviate the tumor hypoxia. More interestingly, it could exorbitantly elevate the autophagy level, which in turn induce excessive activation of autophagy for promoting the therapeutic efficacy. As a result, accompanied with suppressing O2-consumption and triggering pro-death autophagy strategy, the HHBP achieves remarkable antitumor activity, which has been systematically validated both in vivo and in vitro assays. Conclusion: This work not only provides a reduce expenditure strategy for enduring SDT, but also represents an inquisitive strategy for tumor treatments via inducing pro-death autophagy.

Correction: Biodegradable reduce expenditure bioreactor for augmented sonodynamic therapy via regulating tumor hypoxia and inducing pro‑death autophagy

“…org/ 10. 1186/ s12951-021-01166-y Following publication of the original article [1], the authors identified an error in Fig. 6d.…”