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The complex structure and unique components of tumors form a special tumor microenvironment (TME), which plays a vital role in tumor occurrence, development, and metastasis
.
Moreover, it is easy to induce tumors to develop tolerance to various treatments, which often results in unsatisfactory treatment effects
.
Hypoxia is an important sign of the special microenvironment of tumors.
Tumor cells in a hypoxic state will undergo adaptive proteomics and genomics changes to help malignant tumors survive under hypoxic and hypotrophic conditions, such as upregulating angiogenesis Factors and other factors promote tumor angiogenesis to alleviate the state of hypoxia
.
However, over-expression of angiogenesis factors can lead to the formation of malformed and immature vascular structures, which make it more difficult to meet the oxygen demand of tumor tissues, thus forming a vicious circle of hypoxic microenvironment, random angiogenesis, and tumor deterioration.
This makes it more difficult to deliver and penetrate all kinds of therapeutic drugs in this malignant system
.
In response to the above problems, the National Biomedical Materials Engineering Technology Research Center/School of Biomedical Engineering Professor Nie Yu’s research group and Professor Shuai Xintao of Sun Yat-sen University based on the pre-tumor immune microenvironment remodeling (Nanoscale, 2020, 19; 12:22615) and drugs The research of carrier-integrated gene delivery system (Nanoscale Adv.
, 2019, 1:498-507), designed a siHIF-1α lipopeptide with branched arginine as the hydrophilic part and candesartan prodrug as the hydrophobic part The delivery system (RSCD) is used to synergistically inhibit the angiotensin Ang II and the HIF-1α gene that changes in tumor cells in response to hypoxia
.
It is planned to simultaneously weaken the stress feedback of tumor cells and new blood vessels to the hypoxic microenvironment to block all links in the vicious cycle, and then reshape the tumor microenvironment to improve the effect of tumor treatment
.
The results showed that siHIF-1α was down-regulated by 70%, which alleviated the tumor's stress response to hypoxia; candesartan relieves vascular tension, and cooperates with siHIF-1α to down-regulate the secretion of VEGF and inhibit the formation of a cascade of angiogenesis
.
After the administration, the coverage of vascular endothelial cells and pericytes can be increased, the blood vessels of the tumor tend to be normalized, the hypoxia condition in the tumor is obviously improved, and it has a certain inhibitory effect on the tumor growth of the tumor-bearing mice
.
Further combined with chemotherapy drugs doxorubicin or Ce6 liposome photodynamic therapy, it is found that after reshaping the tumor microenvironment, it can increase the enrichment of therapeutic drugs at the tumor site, increase the proportion of tumor tissue apoptosis, and significantly improve chemotherapy and photodynamics The efficacy of treatment
.
The work was jointly completed by Chen Xiaobing, a PhD student in the research group of Professor Nie Yu, and Jin Rongrong, an associate researcher
.
Related work was funded by the National Key Research and Development Program of the Ministry of Science and Technology, the National Natural Science Foundation of China, and Sino-German cooperative research projects
.
Paper information: Delivery of siHIF-1α to Reconstruct Tumor Normoxic Microenvironment for Effective Chemotherapeutic and Photodynamic Anticancer TreatmentsXiaobing Chen, Rongrong Jin, Qian Jiang, Qunjie Bi, Ting He, Xu Song, Matthias Barz, Hua Ai, Xintao Shuai*, Yu Nie* SmallDOI: 10.
1002/smll.
202100609 Click "Read the original text" in the lower left corner to view the original text of the paper
.
The Small Journal introduces "Micron or Nano: No material can be underestimated"
.
Adhering to this philosophy, since its inception in 2005, Small magazine under Wiley has been committed to publishing and disseminating research results involving micro- and nano-materials, whether theoretical or experimental, whether focused or integrated
.
In recent years, the influence and reputation of Small magazine has increased year by year, and the latest impact factor has reached 11.
459
.
The content of the manuscript and reader groups have covered many fields such as physics, chemistry, biology, and engineering
.
WILEYAdvancedScienceNewsWiley’s official WeChat platform for scientific research information long press the QR code to follow us to share cutting-edge information｜Focus on scientific research trends to publish scientific research news or apply for information sharing, please contact: ASNChina@Wiley.
com
.
Moreover, it is easy to induce tumors to develop tolerance to various treatments, which often results in unsatisfactory treatment effects
.
Hypoxia is an important sign of the special microenvironment of tumors.
Tumor cells in a hypoxic state will undergo adaptive proteomics and genomics changes to help malignant tumors survive under hypoxic and hypotrophic conditions, such as upregulating angiogenesis Factors and other factors promote tumor angiogenesis to alleviate the state of hypoxia
.
However, over-expression of angiogenesis factors can lead to the formation of malformed and immature vascular structures, which make it more difficult to meet the oxygen demand of tumor tissues, thus forming a vicious circle of hypoxic microenvironment, random angiogenesis, and tumor deterioration.
This makes it more difficult to deliver and penetrate all kinds of therapeutic drugs in this malignant system
.
In response to the above problems, the National Biomedical Materials Engineering Technology Research Center/School of Biomedical Engineering Professor Nie Yu’s research group and Professor Shuai Xintao of Sun Yat-sen University based on the pre-tumor immune microenvironment remodeling (Nanoscale, 2020, 19; 12:22615) and drugs The research of carrier-integrated gene delivery system (Nanoscale Adv.
, 2019, 1:498-507), designed a siHIF-1α lipopeptide with branched arginine as the hydrophilic part and candesartan prodrug as the hydrophobic part The delivery system (RSCD) is used to synergistically inhibit the angiotensin Ang II and the HIF-1α gene that changes in tumor cells in response to hypoxia
.
It is planned to simultaneously weaken the stress feedback of tumor cells and new blood vessels to the hypoxic microenvironment to block all links in the vicious cycle, and then reshape the tumor microenvironment to improve the effect of tumor treatment
.
The results showed that siHIF-1α was down-regulated by 70%, which alleviated the tumor's stress response to hypoxia; candesartan relieves vascular tension, and cooperates with siHIF-1α to down-regulate the secretion of VEGF and inhibit the formation of a cascade of angiogenesis
.
After the administration, the coverage of vascular endothelial cells and pericytes can be increased, the blood vessels of the tumor tend to be normalized, the hypoxia condition in the tumor is obviously improved, and it has a certain inhibitory effect on the tumor growth of the tumor-bearing mice
.
Further combined with chemotherapy drugs doxorubicin or Ce6 liposome photodynamic therapy, it is found that after reshaping the tumor microenvironment, it can increase the enrichment of therapeutic drugs at the tumor site, increase the proportion of tumor tissue apoptosis, and significantly improve chemotherapy and photodynamics The efficacy of treatment
.
The work was jointly completed by Chen Xiaobing, a PhD student in the research group of Professor Nie Yu, and Jin Rongrong, an associate researcher
.
Related work was funded by the National Key Research and Development Program of the Ministry of Science and Technology, the National Natural Science Foundation of China, and Sino-German cooperative research projects
.
Paper information: Delivery of siHIF-1α to Reconstruct Tumor Normoxic Microenvironment for Effective Chemotherapeutic and Photodynamic Anticancer TreatmentsXiaobing Chen, Rongrong Jin, Qian Jiang, Qunjie Bi, Ting He, Xu Song, Matthias Barz, Hua Ai, Xintao Shuai*, Yu Nie* SmallDOI: 10.
1002/smll.
202100609 Click "Read the original text" in the lower left corner to view the original text of the paper
.
The Small Journal introduces "Micron or Nano: No material can be underestimated"
.
Adhering to this philosophy, since its inception in 2005, Small magazine under Wiley has been committed to publishing and disseminating research results involving micro- and nano-materials, whether theoretical or experimental, whether focused or integrated
.
In recent years, the influence and reputation of Small magazine has increased year by year, and the latest impact factor has reached 11.
459
.
The content of the manuscript and reader groups have covered many fields such as physics, chemistry, biology, and engineering
.
WILEYAdvancedScienceNewsWiley’s official WeChat platform for scientific research information long press the QR code to follow us to share cutting-edge information｜Focus on scientific research trends to publish scientific research news or apply for information sharing, please contact: ASNChina@Wiley.
com
