On October 24, 2019, Nature Communication published the latest work of Prof. Yuliang Zhao's and Prof. Hao Wang's group in the field of nanomedicine research, titled with " A tumour-selective cascade activatable self-detained system for drug delivery and cancer imaging ". A new tumour targeting mechanism based on in vivo self-assembly was reported for the first time by uniting the advantages of small molecules and nanoscience, which showed a great clinical translation potential of nanomedicine.
Traditional molecular chemotherapy and imaging agents have exhibited relatively low effective utilization due to their rapid metabolic clearance. Nanomaterial systems with targeting motifs and size ranges optimized for accumulation greatly enhanced the molecular utilization efficiency. However, the therapeutic efficacy and safety of conventional nanomedicine are hardly to be balanced in clinic. Thus, new strategies with increased accumulation and decreased toxicity are urgently to be developed.
Prof. Hao Wang's group has focused on the development of nanomaterials based on in vivo self-assembly, systematic research on the process and mechanism of in vivo self-assembly of biomaterials, and their application for tumour imaging and therapy. In our previous work, we have proposed the aggregation/assembly induced retention (AIR) effect which can improve the diagnosis and treatment of tumour (Adv. Mater. 2015, 27, 6125, Adv. Mater. 2016, 2, 254, Nano Letters, 2018, 18, 6229, Adv. Mater. 2019, 31, 1807175, Angew. Chem. Int. Ed. Engl. 2019, 131, 15431).
Based on our previous work, we construct a new tumour-selective cascade activatable self-detained system (TCASS) for tumour imaging and therapy. For TCASS, the recognition motif specifically recognized the X-linked inhibitor of apoptosis protein (XIAP), which was overexpressed in cancer cells. Then the recognition motif activated down-stream caspase-3/7, which triggered the self-assembly process. And the fibrous superstructures obtained in cancer cells significantly improved solid tumour accumulation and retention. Meanwhile, the organ competition behavior of the system was comparable to that of small molecules, which were rapidly excreted from the liver and kidneys with decreased toxicity. This work revealed the mechanisms that make this delivery system efficient for accumulation and retention and analyzed the pharmacokinetics of the system (Nat. Commun. 2019, 10, 4861). Besides, as a drug delivery system, TCASS can enhance the therapeutic effects of traditional chemotherapy drugs and reduce their side effects. Finally, this system combined with a NIR probe showed high specificity and sensitivity for detecting bladder cancer in the isolated patient intact bladders, which provided a new tumour targeting mechanism and showed a great clinical translation potential.
Dr. Hong-wei An is the first author of this work, Prof. Yuliang Zhao, Prof. Hao Wang and Prof. Wanhai Xu supervised the entire project as corresponding authors. This work was financially supported by the National Natural Science Foundation of China and Key Project of Chinese Academy of Sciences in Cooperation with Foreign Enterprises.
Article link: https: //www.nature.com/articles/s41467-019-12848-5
On October 24, 2019, Nature Communication published the latest work of Prof. Yuliang Zhao's and Prof. Hao Wang's group in the field of nanomedicine research, titled with " A tumour-selective cascade activatable self-detained system for drug delivery and cancer imaging ". A new tumour targeting mechanism based on in vivo self-assembly was reported for the first time by uniting the advantages of small molecules and nanoscience, which showed a great clinical translation potential of nanomedicine.
Traditional molecular chemotherapy and imaging agents have exhibited relatively low effective utilization due to their rapid metabolic clearance. Nanomaterial systems with targeting motifs and size ranges optimized for accumulation greatly enhanced the molecular utilization efficiency. However, the therapeutic efficacy and safety of conventional nanomedicine are hardly to be balanced in clinic. Thus, new strategies with increased accumulation and decreased toxicity are urgently to be developed.
Prof. Hao Wang's group has focused on the development of nanomaterials based on in vivo self-assembly, systematic research on the process and mechanism of in vivo self-assembly of biomaterials, and their application for tumour imaging and therapy. In our previous work, we have proposed the aggregation/assembly induced retention (AIR) effect which can improve the diagnosis and treatment of tumour (Adv. Mater. 2015, 27, 6125, Adv. Mater. 2016, 2, 254, Nano Letters, 2018, 18, 6229, Adv. Mater. 2019, 31, 1807175, Angew. Chem. Int. Ed. Engl. 2019, 131, 15431).
Based on our previous work, we construct a new tumour-selective cascade activatable self-detained system (TCASS) for tumour imaging and therapy. For TCASS, the recognition motif specifically recognized the X-linked inhibitor of apoptosis protein (XIAP), which was overexpressed in cancer cells. Then the recognition motif activated down-stream caspase-3/7, which triggered the self-assembly process. And the fibrous superstructures obtained in cancer cells significantly improved solid tumour accumulation and retention. Meanwhile, the organ competition behavior of the system was comparable to that of small molecules, which were rapidly excreted from the liver and kidneys with decreased toxicity. This work revealed the mechanisms that make this delivery system efficient for accumulation and retention and analyzed the pharmacokinetics of the system (Nat. Commun. 2019, 10, 4861). Besides, as a drug delivery system, TCASS can enhance the therapeutic effects of traditional chemotherapy drugs and reduce their side effects. Finally, this system combined with a NIR probe showed high specificity and sensitivity for detecting bladder cancer in the isolated patient intact bladders, which provided a new tumour targeting mechanism and showed a great clinical translation potential.
Dr. Hong-wei An is the first author of this work, Prof. Yuliang Zhao, Prof. Hao Wang and Prof. Wanhai Xu supervised the entire project as corresponding authors. This work was financially supported by the National Natural Science Foundation of China and Key Project of Chinese Academy of Sciences in Cooperation with Foreign Enterprises.
Article link: https: //www.nature.com/articles/s41467-019-12848-5
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