The Study Of PH Responsive Biomimetic Nanocarriers For Enhanced Chemotherapeutics Anti-Tumor Activity

Biomimetic camouflage,i.e.,using natural cell membranes for drug delivery,has demonstrated attractive advantages over synthetic materials in both pharmacokinetics and biocompatibility,representing a promising solution for the development of safe nanomedicine,this is mainly based on the important role of various cellular components in the body in physiological and pathological processes.Modifying nanoparticle with the cell membrane of natural origin to endow the nanocarrier some unique advantages,such as biocompatibility,low immunogenicity,reducing the non-specific uptake of nanoparticles by the reticuloendothelial system and prolonging the circulation time of nanoparticles in blood system,most importantly,nanoparticles can be given the ability to actively target lesions.However,only a very limited effort has been dedicated to endowing these nanoparticles with additional functionalities,let alone stimulus-triggered abilities,which is of great importance for the pharmaceutical efficacy of nanomedicines,and it is also important for improving the efficiency of disease treatment in a short period of time.Tumor is an extremely complex complex,including tumor cells,stromal cells and various non-cellular components surrounding.The occurrence,development and metastasis of tumors largely depend on the tumor microenvironment,which is the growth environment of tumor cells.It interacts with tumor cells and causes abnormal metabolism of tumor tissues,which is manifested as hypoxia,high interstitial pressure,weak acidity,a large number of growth factors,proteolytic enzymes and high inflammatory reactions.In recent years,more and more studies have been conducted on using endogenous or exogenous conditions of tumor microenvironment,such as photothermal,magnetic effect and ultrasound,to realize the stimulation responsiveness of nanocarriers.Moreover,both in vivo and in vitro have been verified by the stimulation responsiveness of nanocarriers.However,there is little research in the biomimetic nano-delivery system,which gives the biomimetic membrane drug system a stimulating response.It helps the biomimetic carrier to quickly and efficiently release the chemotherapeutic drug contained in the nanocarrier within the tumor,which is especially important to improve the pharmacokinetic efficiency of biomimetic nano-delivery systems,and this may be the future trend of biomimetic nano drug delivery systems.Therefore,in this paper,we try to use the weak acidity of the tumor microenvironment(pH=6.5~6.8)to help the biomimetic system to achieve pH response and then select the platelets which play an important role in tumorigenesis,growth and metastasis as the main body of the biomimetic membrane.Based on the inherent tendency of platelets to accumulate at wounded sites as well as to interact with tumor cells,platelet membrane has already been utilized as a biomimetic material to endow nanoparticle tumor-targeting capability,We developed a platelet-membrane-infused liposomal drug delivery system through an easy-to-do fusion approach,decorating its shell with a pH-responsive material DSPE-PEOz to allow the product platesome to selectively release its encapsulated drug at designed pH.The biomimetic response drug-loading vehicle was injected into the tumor-bearing mice in the tail vein Once entering the slightly acidic tumor microenvironment and conditions of the enzyme(pH=~5.0),PEOz-platesome could efficiently release its hydrophilic cargoes to kill tumor cells.Our data showed that PEOz-platesome effectively response to acidic pH and could target tumor tissues with high efficiency.Compared with non-responsive platesomes,PEOz-platesome showed significantly higher in vivo anti-tumor activity in two different mouse models,a breast cancer and a colon cancer model respectively.This strategy has the potential to become a general approach to bestow the biomimetic nanoparticles with responsiveness to pH or other specific stimuli(e.g.redox potential,enzyme,hypoxia,ATP,temperature,etc.),with possible application not only in anti-tumor therapy but also for other diseases such as inflammation or cardiovascular disease.