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Despite advances in drug delivery systems (DDSs), the stimuli-responsive controlled release DDSs with high spatial/temperal resolution are still the best choice.Herein, a novel type of envelope-type mesoporous titanium dioxide nanoparticle (MTN) was developed for one-demand drug delivery platform.Docetaxel (DTX) was loaded in the pores of MTN with a high drug loading efficiency (~26%), after that, β-Cyclodextrin (β-CD) was attached to the outer surface and acted as a bulky gatekeeper to block the pores via a reactive oxygen species (ROS) sensitive linker (MTN@DTX-CD).MTN@DTX-CD could entrap the DTX in the pores and allow the rapid release until a focused ultrasound (US) emerged.A large number of ROS were generated by MTN under US radiation, leading to the cleavage of the ROS sensitive linker, thus, DTX could be released rapidly since the gatekeepers (β-CD) were detached.Besides, the generation of ROS could also be used for tumour-specific son dynamic therapy (SDT).Studies have shown the feasibility of MTN@DTX-CD for US-triggered DTX release and son dynamic-chemotherapy.In the in vitro and in vivo studies, by integrating SDT and chemotherapy into one system, MTN@DTX-CD showed excellent antitumor efficacy.More importantly, this novel DDS significantly decreased the side effects of DTX by avoiding the spleen and hematologic toxicity to tumour-bearing mice.