Magnetic chitosan/graphene oxide composite loaded with novel photosensitizer for enhanced photodynamic therapy

Abstract

Photodynamic therapy (PDT) is an increasingly recognized alternative to treat various cancers in clinical practice. Most second-generation photosensitizers (PS) are hydrophobic and have poor targeting selectivity, which limit their efficacy for PDT. In this paper, graphene oxide (GO) coupled with magnetic Fe₃O₄ nanoparticles and chitosan (CS) (MCGO) was prepared by a one-pot solvothermal method and used as a nanocarrier for loading the new photosensitizer HNPa (λ_max = 698 nm), which was first synthesized by our group, and was considered as a good water-soluble drug and an excellent tissue-penetrating agent due to its strong absorption at 698 nm (near-infrared region). The synthesized composite (MCGO–HNPa) showed high stability, good water solubility and biocompatibility, expected magnetic targetability, and good photostability for PDT even in low concentrations. Our research reveals that MCGO nanomaterials can promote the production and release of singlet oxygen (Φ_Δ = 62.9%) when compared with free HNPa. In addition, the in vitro cell uptake experiments suggested that the MCGO nanomaterials can accelerate the penetration of HNPa drugs into the tumor cell nucleus and that the drug release behavior is pH-sensitive. The MTT assay results against human hepatoma cell lines HepG-2 clearly show that the MCGO–HNPa composite can effectively result in cell damage and apoptotic cell death under light, and that the nanocomposite can improve the PDT antitumor effect of PS agents with negligible dark toxicity. Meanwhile, the research on the photoreaction mechanism reveals that Type I and Type II photodynamic reactions can occur simultaneously in this PDT process, and their relative contributions depend on the type and dose of the photosensitizer. Type II has a greater effect on PDT than Type I, especially for a higher HNPa photosensitizer dose. All the results reveal the promising application of the presented novel strategy.