Synthesis of new biodegradable nanocarriers for SN38 delivery and synergistic phototherapy

Objective (s): SN38 is the prominent and effective anticancer drug for treating various types of human cancers such as colorectal, ovarian and lung cancers. SN38 is highly toxic, and due to its poor solubility in aqueous media, and low stability and hydrolysis at physiological pH, it has not been used as an anti-cancer drug. To overcome these problems, SN38 was conjugated with new nanocarriers in order to efficiently deliver it into cancer cells. Materials and Methods: We report the synthesis of nanocarriers based on covalent attachment of graphene oxide with β-cyclodextrin and coordinated with superparamagnetic iron oxide (SPION) nanoparticles for SN38 loading and delivery. Using SPION-functionalized graphene oxide provides magnetic properties and local hyperthermia due to laser irradiation at 808 nm. Structures were characterized by using FT-IR spectroscopy and the size and morphology of the nanoparticles were determined using Malvern Zetasizer and FE-SEM, respectively. Results: The prepared nanoplatform was not significantly toxic to HT-29 cells. However, the developed graphene oxide-based nanocarrier containing SPION and SN38 was used to improve the chemotherapy through photothermal and photodynamic therapy. The optimal laser wavelength (808 nm) for PTT is consistent with that of IR-808 for PDT and the β-CD-GO-EDTA-Fe3O4-SN38 indicated synergistic effects of both drugs and SPION. Conclusion: Biocompatible nanocarrier based on functionalized graphene oxide (β-CD-GO-EDTA-Fe3O4- SN38) demonstrated strong synergistic cytotoxic activity. The new formulation has a great potential as chemo-photothermal-photodynamic therapy agents in synergistic phototherapy