Albumin-binding photosensitizer capable of targeting glioma via the SPARC pathway
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Published on: March 1, 2024
Xingshu Li1, Jae Sang Oh2,3, Yoonji Lee4
1Fujian Provincial Key Laboratory for Cancer Metastasis Chemoprevention and Chemotherapy, College of Chemistry, Fuzhou University, Fuzhou, China.
Background:
Malignant glioma is among the most lethal and frequently occurring brain tumors, and the average survival period is 15 months. Existing chemotherapy has low tolerance and low blood-brain barrier (BBB) permeability; therefore, the required drug dose cannot be accurately delivered to the tumor site, resulting in an insufficient drug effect.
Methods:
Herein, we demonstrate a precision photodynamic tumor therapy using a photosensitizer (ZnPcS) capable of binding to albumin in situ, which can increase the permeability of the BBB and accurately target glioma. Albumin-binding ZnPcS was designed to pass through the BBB and bind to secreted protein acidic and rich in cysteine (SPARC), which is abundant in the glioma plasma membrane.
Results:
When the upper part of a mouse brain was irradiated using a laser (0.2 W cm- 2) after transplantation of glioma and injection of ZnPcS, tumor growth was inhibited by approximately 83.6%, and the 50% survival rate of the treatment group increased by 14 days compared to the control group. In glioma with knockout SPARC, the amount of ZnPcS entering the glioma was reduced by 63.1%, indicating that it can target glioma through the SPARC pathway.
Conclusion:
This study showed that the use of albumin-binding photosensitizers is promising for the treatment of malignant gliomas.
Insights
Precision photodynamic therapy using albumin-binding photosensitizers shows promise for treating malignant glioma. This approach enhances blood-brain barrier permeability and targets tumors via SPARC, significantly inhibiting growth and improving survival rates in mice.
Area of Science:
- Biomedical Engineering
- Oncology
- Nanomedicine
Background:
- Malignant glioma is a lethal brain tumor with poor prognosis.
- Current chemotherapy faces challenges with low tolerance and poor blood-brain barrier (BBB) penetration, limiting efficacy.
- Accurate drug delivery to glioma sites remains a significant unmet need.
Purpose of the Study:
- To develop a precision photodynamic therapy for malignant glioma.
- To utilize an albumin-binding photosensitizer (ZnPcS) for enhanced BBB permeability and targeted glioma delivery.
- To investigate the role of SPARC in mediating ZnPcS uptake in glioma.
Main Methods:
- Design of an albumin-binding photosensitizer (ZnPcS) engineered to cross the BBB.
- Targeting of ZnPcS to glioma via binding with secreted protein acidic and rich in cysteine (SPARC).
- Photodynamic therapy application using laser irradiation on mouse glioma models.
Main Results:
- Photodynamic therapy with ZnPcS inhibited glioma tumor growth by approximately 83.6% in mice.
- The 50% survival rate in the treatment group increased by 14 days compared to controls.
- Targeting via SPARC was confirmed, with a 63.1% reduction in ZnPcS uptake in SPARC-knockout glioma models.
Conclusions:
- Albumin-binding photosensitizers represent a promising strategy for malignant glioma treatment.
- The SPARC pathway is crucial for targeted delivery of ZnPcS to gliomas.
- This approach offers potential for improved therapeutic outcomes in brain cancer.
