Research Of Enzyme-Responsive Nanoparticles For Extracellular Delivery Of Monoclonal Antibodies

With the rise of immunotherapy,the continuous development of tumor therapy in the combination of traditional treatment and the emerging immunotherapy must become the inevitable trend for the future cancer treatment.From the earliest development of tumor antigen vaccine to the CAR-T nowadays,only the monoclonal antibody therapy is a more effective and safe method which has been widely used in clinical treatment.However,due to the off-target effect,low enrichment efficiency and potential toxicity,the immunostimulatory and low bioavailability couldn't be ignored.By use of nano-carrier to transport the monoclonal antibody to the tumor can effectively avoid the above problems.It is worth noting that the monoclonal target is located outside the cell membrane.Under certain conditions,2-Methacryloyloxyethyl phosphorylcholine(MPC)with good biocompatibility can reduce cell adhesion.In this paper,bovine serum albumin(BSA)was firstly used as model to prepare nanocapsules containing pMPC with free radical polymerization.The results showed that the pMPC nanocapsules could inhibit endocytosis,and the higher the surface pMPC content was,the stronger the ability to inhibit the endocytosis.At the same time,enzyme sensitive cross-linker on the surface of nanocapsules could be degraded and release the BSA in the tumor microenvironment of matrix metalloproteinase-2(MMP-2)overexpression.Secondly,the nituzumab was selected as a model.And it was proved that the monoclonal antibody encapsulated by nanocapsules could be retained after being released in the tumor microenvironment.The EGFR locus could be targeted and the expression of downstream proteins was effectively regulated.And this system had a good therapeutic effect on PC 9 type lung adenocarcinoma bearing mice.