Release date: 2017-04-27
Cancer, a malignant tumor, is one of several major diseases that currently threaten human health. Despite decades of in-depth research into the mechanisms and treatments of cancer, the increasing number of cancer cases and the high mortality rates of cancers pose enormous challenges for cancer treatment. Therefore, the development of new cancer treatment methods to achieve safe and effective tumor treatment has become one of the hot issues in many disciplines. Recently, Professor Liu Zhuang from the University of Suzhou collaborated with Prof. Meimei Chen from the University of Macau and Professor Cai Weibo from the University of Wisconsin-Madison to activate the chemotherapy effect of bioreductive drugs by using photodynamic therapy to cause a large area of ​​hypoxia in tumors. Efficient synergistic inhibition of growth.
A large number of studies have shown that solid tumors have insufficient supply of internal oxygen due to rapid proliferation of tumor cells, incomplete vascular development, and uneven distribution, and eventually lead to the presence of hypoxic regions in the tumor. Further studies have found that tumor hypoxia will not only further induce tumor development and metastasis, but also seriously reduce the responsiveness of tumor tissue to conventional chemotherapy, radiotherapy, photodynamic therapy and other treatments, which is a major cause of tumor treatment failure. In addition to trying to improve the efficacy of tumor therapy by regulating the hypoxic condition of tumors, researchers have invented a class of bioreductive drugs that can be converted to toxic chemotherapy drugs under hypoxic conditions to achieve tumors. Selective killing of hypoxic cells. However, due to the heterogeneity of hypoxic conditions in different tumors, such bioreductive drugs cannot achieve radical cure in clinical trials.
Photodynamic therapy uses photoactive molecules to convert molecular oxygen into toxic singlet oxygen by laser irradiation at a suitable wavelength to achieve the killing of tumor cells, so that it can only kill tumor cells in the normoxic region of tumor tissues. It can not effectively kill hypoxic tumor cells; in addition, due to the photodynamic therapy, not only will consume a lot of oxygen but also destroy tumor blood vessels and block the further supply of oxygen at the tumor site. Therefore, the tumor tissue after photodynamic therapy will be more hypoxic, which will be beneficial to the bioreductive drugs. Based on this, in this study, the researchers carried a hydrophobic photoactive molecule (h Ce6) and a hydrophilic bioreductive drug (AQ4N) in the liposome to obtain a long-circulating AQ4N-h Ce6-liposome in vivo. Using the strong optical absorption and fluorescence of h Ce6 molecule in the red region and its ability to chelate the radioisotope (64Cu), the researchers used real-time fluorescence imaging, photoacoustic imaging, and positron emission tomography imaging techniques. Track the pharmacokinetic behavior of AQ4N-h Ce6-liposome in mice. By immunofluorescence staining, it was found that the vascular structure of the mouse tumor was significantly damaged after photodynamic therapy, and the hypoxic condition was more serious than that of the photodynamic treatment group. Further treatment results showed that AQ4N-h Ce6-liposome-mediated photodynamic therapy combined with chemotherapy can effectively inhibit tumor growth, while co-dynamic therapy or AQ4N-mediated chemotherapy alone can only partially inhibit tumor growth. . The strategy shows that by combining photodynamic therapy with bioreductive drugs, it can effectively overcome the effect of tumor hypoxia on the efficacy of photodynamic therapy and achieve safe and effective killing of tumors.
This achievement was recently published in "ACS Nano". The first author of the article is Dr. Feng Liangzhu from Suzhou University.
Http://pubs.acs.org/doi/abs/10.1021/acsnano.6b07525
Source: X-MOL
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