Cancer Cell Membrane-Biomimetic Oxygen Nanocarriers against Tumor Resistance
Malignant tumors greatly threaten human health and challenge current medication. A wealth of clinical evidence indicates that hypoxia is a common feature in most of the solid tumors, and hypoxia leads to drug resistance and poor chemotherapy outcomes. It is appealing to alter tumor hypoxia for improving the chemotherapy outcomes. Hyperbaric oxygen therapy is clinically applied, but it may bring severe side effects caused by high oxygen toxicity. Therefore, a strategy of tumor-specific oxygen delivery is very important for breaking hypoxia-induced chemoresistance with minimized side effects and greatly enhanced therapy efficacy.
Professor CAI Lintao and his colleagues from Shenzhen Institutes of Advanced Technology, Chinese Academy of Science (SIAT), employed nanotechnology to develop a cancer cell membrane-biomimetic oxygen nanocarrier to overcome chemoresistance induced by tumor hypoxia and realize robust oxygen-interference chemotherapy. Hemoglobin and Doxorubicin were co-encapsulated into a polymer as the core that was coated with the cancer cell membrane and PEGylated phospholipid, thus the homologous targeting nanoparticles (DHCNPs) were synthesized. These well-designed nanocarriers retained the cancer cell adhesion molecules on the surface of nanoparticles for homologous targeting and possessed the oxygen-carrying capacity of Hb for oxygen-interfered chemotherapy. Experimental results showed that the nanocarriers not only achieved higher tumor specificity and lowered toxicity by homologous targeting, but also significantly reduced the exocytosis of chemodrugs via suppressing the expressions of hypoxia-inducible factor-1α (HIF-1α), multidrug resistance gene 1 (MDR1) and P-glycoprotein (P-gp), thus resulting in a safe and high-efficient chemotherapy.
This novel design of oxygen nanocarriers is opening up a new pathway for targeted oxygen interference therapy by “fighting cancer with biomimetic cancer”, while providing a new horizon for effective treatment of solid tumors.
The paper titled “Cancer Cell Membrane-Biomimetic Oxygen Nanocarrier for Breaking Hypoxia-Induced Chemoresistance” was published in Advanced Functional Materials on August 18, 2017. This research is supported by the National Natural Science Foundation of China, Guangdong Natural Science Foundation of Research Team and Shenzhen Science and Technology Program.
Figure 1. Cellular functions of cancer cell-biomimetic oxygen nanocarriers (DHCNPs), including homologous targeting, downregulation of predictive markers (HIF-1α, MDR1, and P-gp), and inhibited DOX export. (Image by Prof. CAI Lintao)
Prof. CAI Lintao