Preparation And Research Of Antitumor Property Of Calcium Phosphate Nanoparticles Embedded Platinum Drugs

Platinum-based anticancer drugs are widely used in the clinic for the treatment of a broad spectrum of human malignancies. However, their non-selective reactions with various biomolecules such as proteins and phospholipids and non-specific interactions with both healthy and cancerous tissue will reduce the anticancer efficacy and cause severe adverse side effects. In addition, resistance of cancerous cells to cisplatin, mainly owing to insufficient drug accumulation in tumor cells, frequently occurs after several cycles of treatment, greatly increasing the possibility of the failure of cisplatin in the clinic.In recent years, nano-drug delivery system has shown great potential in cancer therapy. A nano-drug delivery system may effectively improve the tissue distribution and metabolic processes of its loaded drug in the body, leading to reduced side effects, enhanced the efficacy and possibility to overcome the drug resistance. Aming to prepare nanocarriers with the desired physicochemical properties for improved cispaltin therapy, in this paper, we presents a strtegy to prepare cisplatin encapsulated calcium phosphate nanoparticles with the assitance of carboxylated polyme, composing of the following two parts:1. Carboxyl anion （COO-） is able to bind Ca²⁺ and coordinate with cisplatin. We synthesized poly（ethylene glycol）-poly（acrylic acid） （PEG-PAA） to act three roles in prepare cisplatin loaded nanoparticles, including conjugating with cisplatin using a portion of carboxylates of the PAA segment, arresting Ca²⁺ with the residual ones for mineralization of calcium phosphate and providing stability of the formed calcium phosphate nanoparticles by PEG blocks. It was found the calcium phosphate nanoparticles had dimeters about 100 nm and were of core-shell structure with cispatin encapsulated calcium phosphate as the core and PEG as the shell. Further investigations indicated they had good stability in serum-containing solution and were able to release the cisplatin with the trigger of pH. In vitro anticancer experiments showed the calcium phosphate nanoparticle had significant anticancer effects not only to normal but also to cisplatin resistance cancerous cells.2. A platinum（IV）-polymer drugs bearing carboxylates on the backbone were prepared. Then calcium phosphate nanoparticles were prepared by prepcipitation reaction of Ca（NO3）2 and Na2HPO4 in the solution of PEG-PAA and the polymer-platinum drugs. As the polymer-platinum drug does not consume carboxyl group, it was more feasible for regulating the characteristics of the final calcium phosphate nanoparticles comparing with the method previously described. The results showed that the diameters of the calcium phosphate nanoparticles was able to be regulated from 30 nm to 200 nm through varying the Ca²⁺/AA ratio and length of PEG segment. In vitro studies also showed that nanomedicine had improved therapeutic effect on tumor cells.