Abstract
Photodynamic therapy has been increasingly applied in clinical cancer treatments. However, native hypoxic tumoural microenvironment and lacking oxygen supply are the major barriers hindering photodynamic reactions. To solve this problem, we have developed biomimetic artificial red cells by loading complexes of oxygen-carrier (hemoglobin) and photosensitizer (indocyanine green) for boosted photodynamic strategy. Such nanosystem provides a coupling structure with stable self-oxygen supply and acting as an ideal fluorescent/photoacoustic imaging probe, dynamically monitoring the nanoparticle biodistribution and the treatment of PDT. Upon exposure to near-infrared laser, the remote-triggered photosensitizer generates massive cytotoxic reactive oxygen species (ROS) with sufficient oxygen supply. Importantly, hemoglobin is simultaneously oxidized into the more active and resident ferryl-hemoglobin leading to persistent cytotoxicity. ROS and ferryl-hemoglobin synergistically trigger the oxidative damage of xenograft tumour resulting in complete suppression. The artificial red cells with self-monitoring and boosted photodynamic efficacy could serve as a versatile theranostic platform.
Highlights
In past decades, photodynamic therapy (PDT) has emerged as a promising interventional treatment for cancer therapy
When Indocyanine green (ICG) was introduced to clinics, it was reported that more than 98% of ICG bound to proteins in blood, leading to rapid aggregation and clearance from the body[20,21]
Consistent with previous report, the result of native-PAGE electrophoresis and FL detection revealed the co-localization of ICG and Hb, which evidenced the formation of ICG/Hb complexes (Fig. S1b)[20]
Summary
Photodynamic therapy (PDT) has emerged as a promising interventional treatment for cancer therapy. The consumption of oxygen during PDT aggravates tumour hypoxia[6,7], which potentially dampens the therapeutic effect of oxygen-dependent PDT To overcome this hypoxia limitation, various strategies have been explored, including combination with other photodynamic mechanisms, or catalyzing intracellular H2O2 to O2 8,9. We developed a biomimetic lipid-polymer nanoparticle, loading complexes of photosensitizer (indocyanine green, ICG) and oxygen-carrier (Hb), acting as nano-sized artificial red cells to incorporate oxygen supply and monitor the treatment of photodynamic process. These ICG-loaded artificial red cells (I-ARCs), consisted of a lipid layer of lecithin and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-maleimide (polyethylene glycol 2000) (DSPE-PEG) and a core of poly(lactic-co-glycolic acid) (PLGA) encapsulating Hb/ICG complex (Fig. 1a). The fluorescence (FL) of ICG and photoacoustic (PA) response of ICG, HbO2 and Hb would dynamically self-monitor the biodistribution and metabolism of components in I-ARCs during PDT
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