NIR photoregulated theranostic system based on hexagonal-phase
upconverting nanoparticles for tumor-targeted photodynamic therapy and
fluorescence imaging
Abstract
Although photodynamic therapy (PDT) is an effective, minimally-invasive
therapeutic modality with advantages in highly localized and specific
tumor treatments, large and deep-seated cancers within the body cannot
be successfully treated due to low transparency to visible light. To
improve the therapeutic efficiency of tumor treatment in deep tissue and
reduce the side effects in normal tissue, this study developed a
near-infrared (NIR)-triggered upconversion nanoparticle (UCNP)-based
photosensitizer (PS) carrier as a novel theranostics system. The
NaYF4:Yb/Er UCNPs were synthesized by a hydrothermal method, producing
uniformly small size (≈20 nm) nanoparticles and crystalline morphology
of the hexagonal phase. These UCNPs were modified with folic
acid-conjugated biocompatible block copolymers through a bidentate
dihydrolipoic acid linker. The polymer modified hexagonal phase UCNPs
(FA-PEAH-UCNPs) showed an improved dispersibility in the aqueous
solution and strong NIR-to-vis upconversion fluorescence. The
hydrophobic PS, pheophorbide a (Pha), was then conjugated to the stable
vectors through a pH-sensitive linkage. Moreover, these UCNP-based Pha
carriers containing tumor targeting folic acid ligands exhibited the
significantly enhanced cellular uptake efficiency as well as PDT
treatment efficiency. These results suggested that this system could
extend the excitation wavelength of PDT to the NIR region and
effectively improve therapeutic efficiency of PSs.