Research On Anti-cancer Nano-drugs In Response To Tumor Microenvironment

Nanotechnology has begun to play an important role in several of scientific and technological fields.In biomedical applications,nanoparticles open up new horizons,especially for biosensing,targeting delivery therapy and so on.In drug delivery systems(DDS),the design of smart nanocarriers based on tumor microenvironment has been explored.Recently,the development in materials chemistry and drug delivery have made it possible to design stimuli-responsive drug delivery systems.Indeally,the drug delivery systems must overcome multiple biobarriers in the body and achieve long circulation in blood and low toxic side effects in the normal organs.The main content of this paper can be divided into the following two parts:The first part is using the intelligent enzyme-sensitive nanocarriers,the TPGS3350-Pep-DOX&TPGS-Folate enzyme-sensitive micelles containing doxorubicin were developed.The polymer material is divided into three layers.The first is TPGS3350 mainly made of Polyethylene glycol(PEG),which is decorated on the surface of nanocarriers in order to prolong the circulation of nanoparticles in blood;the polypeptide PVGLIG material specifically recognized by the matrix metalloproteinase is linked to TPGS3350 including long-chain PEG3350.Next,the terminal of TPGS3350-Pep can beconjugated with a hydrophobic chemotherapeutic drug(DOX).Furthermore,TPGS-Folate was mixed with TPGS3350-Pep-DOX to form micelle with the film hydration method.Once the polymer material enters the tumor tissue,the long-chain PEG3350 is cleaved by MMPs,and the targetedligand of folic acid is exposed on the surface of micelle.Thus the micelles enter the cell via the folate receptor-mediated endocytosis pathway.The micelle designed in this work poss various functions such as have active targeting,long circulation in the body,easy entry into cells,enhanced anti-tumor effecicay and reduced toxic side effects in normal tissues.The second part we designed intracellular reduction-sensitive TPGS3350-SS-DTX&TPGS3350-FOL nanoparticles,which can respond to the high concentration of GSH inside the tumor cells and cut off the disulfide bond to release the anticancer drug of docetaxel in cells.The nanoparticle significantly improve the anticancer effect of docetaxel and reduce its toxic side effects.The nanoparticles have many multiple functions such as active targeting,long circulation in the body,and rapid release drugs in tumor cells.In the future,such multifunctional intelligent nanoparticles will become promising for cancer therapy.