Calcium Phosphate-Reinforced Photosensitizer-Loaded Polymer Nanoparticles for Photodynamic Therapy

Calcium phosphate-reinforced photosensitizer-loaded polymer nanoparticles have been developed for photodynamic therapy. Chlorine6 (Ce6)-loaded core-shell-corona polymer micelles of poly(ethylene glycol)-b-poly(L-aspartic acid)-b-poly(L-phenylalanine) (PEG-PAsp-PPhe) were employed as template nanoparticles for mineralization with calcium phosphate (CaP). CaP deposition was performed by the electrostatic localization of calcium ions at the anionic PAsp middle shells and the subsequent addition of phosphate anions. CaP-reinforced nanoparticles exhibited enhanced stability. The CaP mineral layer effectively inhibited Ce6 release from the Ce6-loaded mineralized nanoparticles (Ce6-NP-CaP) at physiological pH value. At an acidic endosomal pH value of 5.0, Ce6 release was enhanced, owing to rapid dissolution of the CaP minerals. Upon irradiation of Ce6-NP-CaP-treated MCF-7 breast-tumor cells, the cell viability dramatically decreased with increasing irradiation time. The phototoxicity of Ce6-NP-CaP was much higher than that of free Ce6. Non-invasive optical-imaging results indicated that Ce6-NP-CaP exhibited enhanced tumor specificity compared with free Ce6 and Ce6-loaded non-mineralized polymer nanoparticles (Ce6-NP).