Preparation And Properties In Vitro Of Pt(?) Polymeric Prodrug Nano-calcium Phosphate

Platinum drugs are very effective anti-cancer agents commonly used in clinical practice.And chemotherapy regimens in nearly 50% of cancer patients include platinum drugs.Of them,cisplatin is currently the most widely used platinum drug and is the parent drug for other platinum drugs.It has been shown to treat cancers including lung cancer,ovarian cancer,head and neck cancer,bladder cancer and testicular cancer in clinic.However,its severe toxic and side effects including nephrotoxicity,hematological toxicity,ototoxicity,neurotoxicity,gastrointestinal toxicity,and myelosuppression have severely hin dered its clinical application.After that,researchers have developed Pt???prodrugs by oxidation of Pt???drugs.Studies have shown that these Pt???prodrugs are chemically inert and can reduce the toxic side effects of drugs.However,these Pt???prodrugs still have defects such as high diffusion coefficient and weak load capacity because they are small molecule drugs.Based on this,recently scientists and researchers have developed a novel macromolecular Pt???polymerization prodrug,which has a high and constant drug loading and other advantages.In addition,since calcium phosphate is an important part of the human body,calcium phosphate nanoparticles have been shown to have excellent biocompatibility and biosafety advantages.Therefore,calcium phosphate nanoparticles are often used to encapsulate biological macromolecules such as si RNA and DNA and show advantages in gene therapy effects.Thus,we developed Pt???polymerization prodrug nano-calcium phosphate and studied its in vitro properties.Specifically,we used cisplatin to synthesize Pt???polymerized prodrug PDA and hydrophilic block copolymer PEG_5k-PAA,then reusing PDA's properties similar to biological macromolecules?with numerous negative charges?adsorbed on nano-calcium phosphate by electrostatic adsorption,after that modifying it with PEG_5k-PAA?enhance its solubility under physiological conditions?to prepare Pt???polymerization prodrug nano-calcium phosphate.Finally,we studied the properties of the nano-calcium phosphate particles,such as particle size,stability,drug release,and cytotoxicity in vitro.