Multifunctional nanoparticle PEG-Ce6-Gd for MRI-guided photodynamic therapy

Abstract

Gliomas are one of the most common types of primary brain tumors. Despite recent advances in the combination of surgery, radiotherapy, systemic therapy (chemotherapy, targeted therapy) and supportive therapy in the multimodal treatment of gliomas, the overall prognosis remains poor and the long-term survival rate is low. Thus, it is crucial to develop a novel glioma management method. Due to its relatively non-invasive, selective and repeatable characteristics, photodynamic therapy (PDT) has been investigated for glioma therapy in the past decade, exhibiting higher selectivity and lower side effects compared with those of conventional therapy. However, most of the photosensitizers (PSs) are highly hydrophobic, leading to poor water solubility, rapid degradation with clearance in blood circulation and ultimately, low bioavailability. In the present study, hydrophilic polyethylene glycol (PEG)-chlorin e6 (Ce6) chelated gadolinium ion (Gd ³⁺) nanoparticles (PEG-Ce6-Gd NPs) were synthesized via a chelation and self-assembly process. Initially, the cell cytotoxicity of PEG-Ce6-Gd NPs was evaluated with or without laser irradiation. The in vitro study demonstrated the lack of toxicity of PEG-Ce6-Gd NPs to tumor cells in the absence of laser irradiation. However, its toxicity was enhanced under laser irradiation. Moreover, the size and weight of brain tumors were significantly decreased in mice with glioma xenografts, which was further confirmed via histological analysis. Subsequently, the results indicated that the PEG-Ce6-Gd NPs had a favorable T ₁-weighted contrast performance (0.43 mg ml ⁻¹ s ⁻¹) and were observed to have significant contrast enhancement at the tumor site from 0.25 to 1 h post-injection in vivo. The favorable MRI, as well as the synergetic photodynamic antitumor effect and antineoplastic ability of PEG-Ce6-Gd NPs was identified. It was suggested that PEG-Ce6-Gd NPs had great potential in the diagnosis and PDT treatment of gliomas, and possibly other cancer types, with prospects of clinical application in the near future.