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Abstract
Polymeric micelles of zinc protoporphyrin (ZnPP) with water soluble biocompatible and amphiphilic polymer, polyethylene glycol (PEG) demonstrated unique characteristics to target tumor tissues selectively based on the enhanced permeability and retention (EPR) effect. The micellar macromolecular drug of ZnPP (SMA–ZnPP and PEG–ZnPP) previously showed notable anticancer activity as a consequence of selective tumor targeting ability and its potent HO-1 inhibitory potential, resulting in suppressed biliverdin/bilirubin production in tumors thereby leading to oxystress induced tumor cell killing. Furthermore, recent findings also showed that ZnPP efficiently generated reactive singlet oxygen under illumination of visible light, laser, or xenon light source, which could augment its oxystress induced cell killing abilities. In the present paper, we report the synergistic effects of light induced photosensitizing capabilities and HO-1 inhibitory potentials of these unique micelles when tested in vitro and in vivo on tumor models under localized, mild illumination conditions using a tungsten–xenon light source. The results indicate that these water soluble polymeric micelles of ZnPP portend to be promising candidates for targeted chemotherapy as well as photodynamic therapy against superficial tumors as well as solid tumors located at light penetrable depths.
| Abbreviations | ||
| AUC | = | Area under the concentration-time curve |
| Cpm | = | counts per minute |
| DLS | = | Dynamic light scattering |
| DMBA | = | 7, 12-dimethy bezanthracene |
| DMSO | = | Dimethyl sulphoxide |
| EPR | = | Enhanced permeability and retention |
| ESR | = | Electron spin resonance spectroscopy |
| HO-1 | = | Heme oxygenase-1 |
| Hydroxy-TEMP | = | 4-hydroxy-2,2,6,6-tetramethyl piperidine |
| IC50 | = | The concentration which produce 50% tumor cell growth suppression |
| kDa | = | Kilo Dalton |
| Mw | = | Weight average molecular weight |
| PDI | = | Polydispersity index |
| PDT | = | Photodynamic therapy |
| PEG–ZnPP | = | polyethylene glycol conjugated zinc protoporphyrin |
| ROS | = | Reactive oxygen species |
| SEC | = | Size exclusion chromatography |
| SMA–ZnPP | = | Copoly(styrene–maleic acid)-zinc protoporphyrin micelle |
| ZnPP | = | zinc protoporphyrin |
| Abbreviations | ||
| AUC | = | Area under the concentration-time curve |
| Cpm | = | counts per minute |
| DLS | = | Dynamic light scattering |
| DMBA | = | 7, 12-dimethy bezanthracene |
| DMSO | = | Dimethyl sulphoxide |
| EPR | = | Enhanced permeability and retention |
| ESR | = | Electron spin resonance spectroscopy |
| HO-1 | = | Heme oxygenase-1 |
| Hydroxy-TEMP | = | 4-hydroxy-2,2,6,6-tetramethyl piperidine |
| IC50 | = | The concentration which produce 50% tumor cell growth suppression |
| kDa | = | Kilo Dalton |
| Mw | = | Weight average molecular weight |
| PDI | = | Polydispersity index |
| PDT | = | Photodynamic therapy |
| PEG–ZnPP | = | polyethylene glycol conjugated zinc protoporphyrin |
| ROS | = | Reactive oxygen species |
| SEC | = | Size exclusion chromatography |
| SMA–ZnPP | = | Copoly(styrene–maleic acid)-zinc protoporphyrin micelle |
| ZnPP | = | zinc protoporphyrin |