Oxygen-generating hybrid nanoparticles to enhance fluorescent/photoacoustic/ultrasound imaging guided tumor photodynamic therapy

Abstract

Photodynamic therapy (PDT) is a promising tumor treatment modality that can convert oxygen into cytotoxic singlet oxygen (SO) via photosensitizer to ablate tumor growth. However, the uncontrolled cancer cell proliferation during tumor development and the oxygen consumption during PDT always result in an insufficient oxygen level in tumors, which can adversely affect the PDT efficiency in turn. We designed an oxygen-generating PDT nanocomplex by encapsulating a manganese dioxide nanoparticle (MnO₂ NP) in an indocyanine green (ICG) modified hyaluronic acid nanoparticle (HANP) to overcome this limitation. Because of the excellent fluorescent and photoacoustic properties, the tumor accumulation of the ICG-HANP/MnO₂ (IHM) nanocomplex was monitored by fluorescent imaging and photoacoustic imaging after intravenous administration into the SCC7 tumor-bearing mouse model. Both high fluorescent and photoacoustic signals were detected and found peak at 6 h post-injection (tumor-muscle ratio: 4.03 ± 0.36 for fluorescent imaging and 2.93 ± 0.13 for photoacoustic imaging). In addition, due to the high reactivity of MnO₂ NP to H₂O₂, an unfavorable tumor cell metabolic, the oxygen content in the tumor is elevated 2.25 ± 0.07 times compared to that without IHM treatment as ultrasound imaging confirmed. After laser irradiation, significant tumor growth inhibition was observed in the IHM-treated group compared to the ICG-HANP-treated group, attributed to the beneficial oxygen-generating property of IHM for PDT. It is expected that the design of IHM will provide an alternative way of improving clinical PDT efficacy and will be widely applied in cancer theranostics.

Keywords: Hyaluronic acid particles; Hypoxia; Image-guided therapy; Manganese dioxide nanoparticles; Oxygen generating; Photodynamic therapy.