An Effective Intracellular Delivery System Of Monoclonal Antibody For Treatment Of Tumor:Erythrocyte Membrane-coated Self-associated Antibody Nanoparticles

Antibody-based drugs have attracted more and more attention for their high selectivity,biocompatibility,biodegradability,non-toxicity and non-immunogenicity.They have been widely used in treatment of tumor,autoimmune diseases,virus infection,osteoporosis and respiratory diseases,among which the tumor accounts for the biggest part of the antibody drug.However,currently,the targets of almost all antibody-based drugs so far are biomarkers expressed on cell membrane instead of which inside tumor cells.Due to the lack of effective intracellular delivery strategies for antibodies,a large number of intracellular biomarkers of cancers cannot become effective therapeutic targets of antibodies.Most of the antibody-based anti-tumor drugs will be tarried outside tumor cells after being imported into patients’ body.On the other hand,the short half-life is another problem of antibody-based drugs.Antibody are proteins tend to be degraded by protease.So far there is still no effective solution to stabilize free antibody in the physical environment and prolong the half-life.These two problems cause the development of the antibodies that are specific to intracellular antigens(targets)become difficult.Human telomerase reverse transcriptase(hTERT)is one of biomarkers for tumor which at the same time is an indispensable part for cell immortalization.Tumor can be effectively suppressed by inhibiting hTERT,which,however,is expressed only inside tumor cells instead of on the cell membrane.Currently the methods reported to use for intracellular targeting are intrabody gene expressing and siRNA delivery technology ect..These methods usually have some shortages such as small accessing area,non-efficient gene delivery technology and short half-time.Making anti-hTERT antibody enter the tumor cells efficiently,bind to the intracellular targets specifically and then suppress the tumor activity effectively is a reasonable strategy to target the hTERT biomarker that are inside the cancer cells.The technology in this project here is an intracellular antibody delivery platform technology,which could apply to any antibodies that target the intracellular therapeutic biomarkers of any cells.It is also a good idea to make other antigens express inside tumor cells to become effective targets if we use this technology more widely.Therefore,in this project,the anti-hTERT blocking monoclonal antibody will be prepared into antibody nanoparticles,followed by the encapsulation of erythrocyte membrane(EM)to form the anti-hTERT antibody nanoparticles delivery system.The advantages of this technology is that the EM encapsulation can increase the stability of antibody,and prolong the half-life of nanoparticles.Besides,due to the change of intracellular delivery pathway,EM encapsulated antibody nanoparticles can be delivered intracellularly,and release antibody into the cells effectively.It also has some other advantages like increasing antibody retention inside tumor tissue.This research will provide an effective method for the delivery of antibody into cells and make it possible to be a potential and effective antibody drug for targeting intracellular therapeutic biomarkers.