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Mammary-Derived Growth Inhibitor Targeting Peptide-Modified PEG-PLA Nanoparticles for Enhanced Targeted Glioblastoma
Xingye Feng1, Xiaoling Gao2, Ting Kang1
1†Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, PR China.
Abstract:
Targeting delivery of chemotherapeutics to neovasculature represents a promising means for tumor therapy since angiogenesis has been a featured hallmark of glioblastma. However, anti-angiogenic therapy would induce the occurrence of metastatic tumor and even neoplasm recurrence. Simultaneous targeting of tumor cells and neovasculature perfectly overcome such defects and has been proven to be an efficacious strategy for suppressing tumor growth. In the present study, a tumor homing peptide CooP selective binding to mammary-derived growth inhibitor that overexpressed in glioma cells and blood vessel endothelial cells was decorated on the surface of paclitaxel-loading PEG-PLA nanoparticles (NP-PTX) to obtain the dual targeting nanovector CooP-NP-PTX. In vitro antiproliferation study showed that HUVEC cells and U87MG cells were much more sensitive to CooP-NP-PTX than NP-PTX. In vivo imaging demonstrated that CooP-NP accumulated more selectively and penetrated deeper into the tumor site. In addition, the glioma-bearing mice treated with CooP-NP-PTX achieved the longest survival time compared to NP-PTX and Taxol. The findings observed above indicated that CooP peptide-functionalized anti-neoplastic agent-loaded nanoparticles might possess promising potential for glioblastoma therapy.
Insights
This study developed dual-targeting nanoparticles (CooP-NP-PTX) for glioblastoma therapy. These nanoparticles effectively target both tumor cells and blood vessels, significantly improving survival rates in mice.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Angiogenesis is a hallmark of glioblastoma, making neovasculature a therapeutic target.
- Anti-angiogenic therapy can lead to tumor metastasis and recurrence.
- Simultaneous targeting of tumor cells and neovasculature offers a strategy to overcome these limitations.
Purpose of the Study:
- To develop a dual-targeting nanovector for enhanced glioblastoma therapy.
- To functionalize paclitaxel-loaded nanoparticles with a tumor-homing peptide (CooP).
- To evaluate the efficacy of CooP-NP-PTX in vitro and in vivo.
Main Methods:
- Decorating paclitaxel-loaded PEG-PLA nanoparticles (NP-PTX) with CooP peptide.
- Assessing in vitro antiproliferation effects on HUVEC and U87MG cells.
- Conducting in vivo imaging and survival studies in glioma-bearing mice.
Main Results:
- CooP-NP-PTX exhibited enhanced sensitivity in HUVEC and U87MG cells compared to NP-PTX.
- In vivo imaging showed selective accumulation and deeper penetration of CooP-NP into tumors.
- Glioma-bearing mice treated with CooP-NP-PTX demonstrated the longest survival.
Conclusions:
- CooP peptide-functionalized nanoparticles show promise for glioblastoma treatment.
- Dual targeting of tumor cells and neovasculature improves therapeutic outcomes.
- This nanovector strategy offers a potential advancement in cancer therapy.
