ABSTRACT
@#Drug transportation is impeded by various barriers in the hypoxic solid tumor, resulting in compromised anticancer efficacy. Herein, a solid lipid monostearin (MS)-coated CaO2/MnO2 nanocarrier was designed to optimize doxorubicin (DOX) transportation comprehensively for chemotherapy enhancement. The MS shell of nanoparticles could be destroyed selectively by highly-expressed lipase within cancer cells, exposing water-sensitive cores to release DOX and produce O2. After the cancer cell death, the core-exposed nanoparticles could be further liberated and continue to react with water in the tumor extracellular matrix (ECM) and thoroughly release O2 and DOX, which exhibited cytotoxicity to neighboring cells. Small DOX molecules could readily diffuse through ECM, in which the collagen deposition was decreased by O2-mediated hypoxia-inducible factor-1 inhibition, leading to synergistically improved drug penetration. Concurrently, DOX-efflux-associated P-glycoprotein was also inhibited by O2, prolonging drug retention in cancer cells. Overall, the DOX transporting processes from nanoparticles to deep tumor cells including drug release, penetration, and retention were optimized comprehensively, which significantly boosted antitumor benefits.
ABSTRACT
Hypoxia, a salient feature of most solid tumors, confers invasiveness and resistance to the tumor cells. Oxygen-consumption photodynamic therapy (PDT) suffers from the undesirable impediment of local hypoxia in tumors. Moreover, PDT could further worsen hypoxia. Therefore, developing effective strategies for manipulating hypoxia and improving the effectiveness of PDT has been a focus on antitumor treatment. In this review, the mechanism and relationship of tumor hypoxia and PDT are discussed. Moreover, we highlight recent trends in the field of nanomedicines to modulate hypoxia for enhancing PDT, such as oxygen supply systems, down-regulation of oxygen consumption and hypoxia utilization. Finally, the opportunities and challenges are put forward to facilitate the development and clinical transformation of PDT.
ABSTRACT
The routine management of head injury includes hyperventilation to produce hypocapnis with arterial CO2 tension 25~30 torr. But a decrease in cerebral blood flow with hypocapnia may result in cerebral ischemia. Our study was to evaluate the change of cerebral blood flow during hyperventilation in halthane anesthesia. The jugular venous oxygen saturation(SjvO2), arterio-venous oxygen content difference(CaO2-CjvO2), and oxygen extraction ratio(O2ER) were used as criteria of cerebral ischemia with reduced cerebral blood flow. The results are as follows: 1) SjvO2 was lower in group 2(PaCO2=22.8torr) than group 1(PaCO2=30.3 torr). 2) CaO2-CjvO2 and O2ER were higher in Group 2 than group 1. 3) No more increased possibility of cerebral ischemia with reduced cerebral blood flow was observed Group 2 than group 1.