Synthesis Of PH Or Redox-sensitive Hyperbranched Polyphosphoester For Cancer Therapy

Polymer nanocomposites carrier as active compounds like small drug molecules,peptides or gene delivery carrier,has attracted wide attention of scientists.The nanometer carrier can significantly enhance not only some properties of drugs,such as water soluble,biocompatibility,and can increase the long cycle,and so on,and they can through reasonable chemical design,the characteristics of the organization,parts,or cells,through specific stimulating factor,intelligent drug delivery and release,this is also known as intelligent responsive drug delivery system.These specific stimulation factors including p H,temperature,enzyme,light and ultrasonic,etc.,can be divided into endogenous and exogenous,some of these reactions is naturally occurring in the body.Endogenous stimuli including,reductive environment,enzymes,etc;Exogenous stimuli including light,ultrasound,magnetic field,etc.The response of endogenous or exogenous nanometer carrier delivery drugs has very good application potential.But has yet to have a responsive nanometer carrier can be applied to clinical,causes include design complex,difficult to enlarge,part of the nanometer carrier biocompatibility remains to be improved.Development of promising responsiveness nanometer carrier become urgent needs.In this article,we mainly study intracellular micro nanometer carrier of environmental response.Combining the advantage of the hyperbranched poly phosphate nanometer carrier,such as phosphate biodegradable,branched properties of the hyperbranched nanodrugs are better able to load,and give its responsiveness,we will be introduced to the sensitive chemical bonds of polyethylene glycol modified hyperbranched poly phosphate system,and continuously modified to carrier.We mainly according to the following characteristics of the tumor microenvironment selective introduction of responsiveness chemical bonds.First,disulfide bond,can quickly be glutathione(GSH)fracture,or reducing the enzyme outside the cell oxidation conditions remain stable,can be used to realize reducing sensitivity.Intracellular drug release can be targeted by different concentration of GSH,known in the tumor tissue extracellular GSH concentration(~ 2-10 u M),cells(~ 2-10 m M).Secondly,due to the endosome,dissolving enzyme in vivo environment(~ 5.4),emerged a large number of anticancer drug delivery system.And photosensitizer treatment due to its selectivity of space-time and non-invasive,has good application prospect.There are some photosensitizer has to clinical.And high concentration of photosensitizer or ROS productivity of photosensitizer has better ability to suppress tumor growth,but avoid the produce light toxicity,we designed and synthesized acid response of hyperbranched nano materials,in the p H(5.4)particles under the condition of rapid disintegration,in vitro drug release good responsiveness of delivering drugs to verify the material,and through the package carrier photosensitizer Ce6 inspection of fluorescent material has good found the Ce6 fluorescence quenching characteristic,so we assume package load with high Ce6 and won't produce light toxicity to normal cells,the connotation of the tumor body acidity released,tumor site,fixed point light produce high concentrations of Ce6 efficient killing tumor cells.