| Photodynamic therapy (PDT) in tumors is a relatively new treatment, which involves the activation of the molecular oxygen under irradiation by light in the presence of certain photodrugs (photosensitizers) that have been selectively accumulated in the target tissue. In comparison with surgery, chemotherapy, radiation and other conventional treatment methods, PDT is considered to be a clinical treatment with high safety, few side effects, reliable repeatability, and relatively low cost. PDT relies on the application of a photosensitizer which is activated by light. The activated sensitizer reacts with the oxygen present in the tissue, which forms highly toxic radicals and then induces tissue necrosis/apoptosis. Thus photosensitizer is one of the main factors in determining the efficiency of PDT. Despite progressive development in photosensitizer, a few problems still exist, such as relatively weak absorption in the red region of visible light, poor water-solubility, and high dark toxicity. The absorption range of most photosensitizers is below 650 nm, which seriously hinders their clinical application.Benefiting from the strong absorption band in the red light region, Chlorin e6 (Ce6) emerges as a prospective photosensitizer for PDT. Ce6 exhibits a strong absorption peak at a wavelength of 663 nm, low cytotoxicity, and almost no side effect to skin. Furthermore, it can reach deeper penetration of tissue and produce higher reactive oxygen species (ROS). For an efficient PDT, photosensitizer must travel through the blood stream with high water-stability. However, Ce6 is a hydrophobic drug and insoluble in water, which greatly reduces its PDT effects. To overcome this problem, hydrophilic macromolecules such as poly(vinyl pyrrolidone) (PVP), poly(ethylene glycol) (PEG) and various polypeptides were frequently used to improve the solubility of Ce6. Unfortunately, the drug loading content (DLC) of these approaches was lower than 15%. Furthermore, the cancer-killing effect of these complexes was usually lower than that of free Ce6. Therefore, an ideal Ce6 delivery system with good water-solubility and high DLC is still required.In this study, an efficient Ce6 delivery system with 128% DLC was developed based on the noncovalent interactions between Ce6 and single wall carbon nanotubes (SWCNTs). Owing to nanoscale diameters, SWCNTs show a very large specific surface area, which provides the opportunity for the construction of excellent drug delivery systems with satisfied drug loading capacities. Considering the existence of large aromatic conjugation structures of Ce6 and SWCNTs, Ce6 was adsorbed onto SWCNTs by strong noncovalentπ-πinteractions with a high efficiency. Chitosan molecules chains contain a lot of amino (-NH2) and hydroxyl (-OH) groups, which can increase the water-solubility of SWCNTs. Therefor, the low molecular weight chitosan was chosen to wrap the Ce6-SWCNT complexes by noncovalentπ-πinteractions to gain water-soluble drug delivery system. The biological evaluation showed that chitosan-wrapped Ce6-SWCNT complexes (Chitosan-Ce6-SWCNTs) exhibited better cell uptake and a higher anticancer effect against HeLa cells than free Ce6. |
PDF Full Text Request