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Multifunctional nanoparticle PEG‑Ce6‑Gd for MRI‑guided photodynamic therapy
Dan Xu1, Aju Baidya1, Kai Deng2
1Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei 430071, P.R. China.
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 (Gd3+) 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 T1‑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.
Insights
Novel hydrophilic nanoparticles combining polyethylene glycol (PEG)‑chlorin e6 (Ce6) and gadolinium (Gd3+) show promise for glioma treatment. These PEG‑Ce6‑Gd nanoparticles are non-toxic without laser but effective against tumors with laser, offering potential for improved brain tumor management.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Gliomas are aggressive primary brain tumors with poor prognosis despite multimodal treatments.
- Photodynamic therapy (PDT) offers a selective, non-invasive approach for glioma treatment, but photosensitizer limitations hinder efficacy.
- Hydrophobic photosensitizers lead to poor solubility, rapid clearance, and low bioavailability, necessitating improved delivery systems.
Purpose of the Study:
- To synthesize and evaluate novel hydrophilic polyethylene glycol (PEG)‑chlorin e6 (Ce6) chelated gadolinium ion (Gd3+) nanoparticles (PEG‑Ce6‑Gd NPs) for glioma diagnosis and therapy.
- To assess the in vitro cytotoxicity and in vivo therapeutic efficacy of PEG‑Ce6‑Gd NPs in a mouse glioma model.
- To investigate the magnetic resonance imaging (MRI) properties and combined diagnostic and therapeutic potential of the developed nanoparticles.
Main Methods:
- Synthesis of hydrophilic PEG‑Ce6‑Gd NPs via chelation and self-assembly.
- In vitro cytotoxicity assays of PEG‑Ce6‑Gd NPs with and without laser irradiation.
- In vivo studies in mice with glioma xenografts, including tumor size/weight assessment, histological analysis, and MRI.
- Evaluation of T1-weighted contrast performance and in vivo contrast enhancement.
Main Results:
- PEG‑Ce6‑Gd NPs exhibited no significant toxicity to tumor cells without laser irradiation but showed enhanced cytotoxicity upon laser activation.
- Significant reduction in brain tumor size and weight was observed in mice treated with PEG‑Ce6‑Gd NPs and laser.
- The nanoparticles demonstrated favorable T1-weighted MRI contrast performance and significant tumor-site enhancement post-injection.
- Synergistic photodynamic antitumor effects and antineoplastic capabilities were identified.
Conclusions:
- Hydrophilic PEG‑Ce6‑Gd NPs are effective and selective for glioma treatment via photodynamic therapy.
- The nanoparticles possess excellent MRI contrast properties, enabling combined diagnosis and therapy.
- PEG‑Ce6‑Gd NPs show significant potential for clinical application in glioma management and other cancers.
