Encapsulation of cisplatin in a pegylated calcium phosphate nanoparticle (CPNP) for enhanced cytotoxicity to cancerous cells.

HYPOTHESIS: Exchange of the chloride ion (Cl-) ligands of cisplatin with carboxylates is widely used in fabricating cisplatin loaded nanoparticles for improved cancer therapy. However, the dynamic exchange may cause premature cisplatin release and even disintegration of the nanoparticles in Cl--containing medium such as in plasma. Molecules bearing carboxylates are capable of mediating the mineralization process of calcium phosphate; therefore, it is possible to overcome the disadvantage by sequestering cisplatin in a calcium phosphate nanoparticle (CPNP). EXPERIMENTS: With the hypothesis, precipitation reaction of calcium nitrate and disodium hydrogen phosphate was performed in a solution of poly(ethylene glycol)-poly(acrylic acid) block copolymers with their carboxylates partly conjugated with cisplatin. Then, structure, physicochemical properties, and bioactivity of the product were carefully investigated with multiple characterization methods. FINDINGS: It was revealed a pegylated, cisplatin encapsulated CPNP was prepared; and with appropriate mole ratio of cisplatin to carboxylates, the nanoparticle encapsulated cisplatin efficiently (>90%), was stable and almost entirely prevented the cisplatin release in Cl--containing medium at pH 7.4 but released them in an acidic condition, and showed moderately and greatly enhanced cytotoxicities to the lung cancer cell line A549 and its cisplatin resistance form A549R respectively in comparison with the free cisplatin.

A Method to Encapsulate Small Organic Molecules in Calcium Phosphate Nanoparticles Based on the Supramolecular Chemistry of Cyclodextrin.

Calcium phosphate nanoparticles (CPNPs) encapsulating small organic molecules, such as imaging agents and drugs, are considered to be ideal devices for cancer diagnosis or therapy. However, it is generally difficult to encapsulate small organic molecules in CPNPs because of the lack of solubility in water or binding affinity to calcium phosphate. To solve these issues, we utilized the carboxymethyl ß-cyclodextrin (CM-ß-CD) to increase the solubility and binding affinity to small organic molecules for the encapsulation into CPNPs in this work. The results indicated that the model molecules, hydrophilic rhodamine B (RB) and hydrophobic docetaxel (Dtxl), are successfully encapsulated into CPNPs with the assistance of CM-ß-CD. We also demonstrated the CPNPs could be remarkably internalized into A549 cells, resulting in the efficient inhibition of tumor cells' growth.