With the development of nano biotechnology and nano medicine, the concept of in-situ supramolecular assembly of bioactive molecules has attracted more and more attention. It is of great significance for improving the biological effect and safety of materials in vivo to realize the controllable assembly and control of polymers.
However, due to the complex biological process of biomedical materials in vivo, how to realize the assembly and regulation of polymers under the physiological conditions of disease is a very challenging scientific problem in the field of medical polymers. The in-depth study of the basic problems of these chemical materials is very important to clarify the absorption, distribution, transport and metabolism of polymer materials in vivo.
Wang Hao research group of national nano science center of Chinese Academy of Sciences has been committed to the development of new biological nano materials for in-situ self-assembly in vivo, and has carried out systematic research on the assembly process and mechanism of biological nano materials, and explored their application in tumor imaging and treatment (adv. mater. 2015, 276125; NAT. Commun. 2017, 81276; adv. Mater. 20181804971; adv Mater. 2019， 1807175）。
How to realize the deep penetration and effective enrichment of nanodrugs in tumor is one of the key scientific problems to be solved in the current cancer treatment. Researchers Wang Hao and Qiao zengying have developed a temperature sensitive polypeptide polymer, which is in a single molecular state in the blood circulation. Because of its small size, it can penetrate deeply into the tumor.
By using the combination of temperature sensitive polymer and photothermal molecules, the in-situ self-assembly of polypeptide polymer in the tumor site is realized under near-infrared irradiation, effectively improving the permeation of nanodrugs in the tumor site Permeability and enrichment efficiency (nano lett. 2018, 186577-6584). Because the microenvironment of tumor is acidic, the self-assembled polypeptide polymer was designed and synthesized under the condition of weak acid.
The pH responsive polypeptide polymer can penetrate into the deep part of solid tumor in the form of single chain, and gather under the stimulation of weak acid in tumor microenvironment, so as to recover the higher ability of materials to enter into cells, thus realizing the efficient killing of internal cells of solid tumor (angelw. Chem. Int. ed. 2019, 584632-4637).
The assembly behavior in vivo is a very complex process, and people are facing a great challenge that how to design molecular units to precisely regulate the assembly process in vivo, so as to improve the pharmaceutical function. Wang Hao, Qiao zengying and Cheng Dongbing realized the effective enrichment of nanodrugs in tumor site by using the regulation strategy of in vivo recombination.
The nanoparticles connected with anticancer drugs are recombined in tumor site to form primary nanofibers, which can play the role of "seed", further promote the morphological transformation of nanoparticles, significantly accelerate the growth rate of nanofibers, so as to realize the accelerated accumulation of anticancer drugs in tumor site, and provide a new strategy for improving the enrichment of drugs in tumor site (j.am.chem.soc 2019， 141， 4406-4411）。
Based on the regulation of recombinant assembly, ROS responsive polypeptide polymers were further developed, which can be assembled into nanofibers in mitochondria. In the process of morphological transformation, therapeutic peptides can interact with mitochondrial membrane through multiple sites, which greatly enhances the destruction of mitochondrial membrane, thus effectively improving the therapeutic effect of tumor (j.am.chem.soc. 2019, DOI: 10.1021/jacs.1028b07727, cover chapter). This series of featured work has attracted wide attention and was invited to write an overview (acc. chem. Res. 2019, 52367-378).