Hypoxia, the typical and conspicuous characteristic of most solid tumors, worsens the tumor invasiveness and metastasis. Here, we engineered a sequential ultrasound (US)/hypoxia-sensitive sonochemotherapeutic nanoprodrug by initially synthesizing the hypoxia-activated azo bond-containing camptothecin (CPT) prodrug (CPT2-Azo) and then immobilizing it into the mesopores of sonosensitizer-integrated metal organic frameworks (MOF NPs). Upon entering the hypoxic tumor microenvironment (TME), the structure of CPT2-Azo immobilized MOFs (denoted as MCA) was ruptured and the loaded nontoxic CPT2-Azo prodrug was released from the MOF NPs. Under US actuation, this sonochemotherapeutic nanoprodrug not only promoted sonosensitizer-mediated sonodynamic therapy (SDT) via the conversion of oxygen into cytotoxic reactive oxygen species (ROS) but also aggravated hypoxia in the TME by elevating oxygen consumption. The exacerbated hypoxia in turn served as a positive amplifier to boost the activation of CPT2-Azo, and the controllable release of toxic chemotherapeutic drug (CPT), and compensated the insufficient treatment efficacy of SDT. In vitro and in vivo evaluations confirmed that sequential SDT and tumor hypoxia-activated sonochemotherapy promoted the utmost of tumor hypoxia and thereby contributed to the augmented antitumor efficacy, resulting in conspicuous apoptotic cell death and noteworthy tumor suppression in vivo. Our work provides a distinctive insight into the exploitation of the hypoxia-activated sonochemotherapeutic nanoprodrug that utilizes the hypoxic condition in TME, a side effect of SDT, to initiate chemotherapy, thus causing a significantly augmented treatment outcome compared to conventional SDT.
The governance of state-owned enterprises (SOEs) is hybrid in nature as it combines mechanisms of public administration, informal political interference, and standard corporate governance. While researchers often consider social enterprises as hybrid organizations and offer a favorable evaluation of these hybrid characteristics, the similar characteristics in SOEs are oftentimes viewed as their vulnerability. Prior discussions about SOE governance tend to focus on standard corporate governance mechanisms and treat the distinct SOE governance practices as “deviations” from these standard governance mechanisms. By considering SOE governance as hybrid, we bring attention to the existence of alternative governance mechanisms that the state can rely on, such as governance through performance contracts, intermediate ownership structures, and informal influence by politicians. We examine governance hybridity from a variety of theoretical perspectives used in prior research on SOE governance. We also discuss how hybrid governance arrangements in SOEs vary within and across countries. We conclude the chapter with directions for future research on the hybrid governance of SOEs.
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