Stimuli-responsive nanoparticles with tailorable elastin-like polypeptide chains for improved brain tumor targeting...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Oncology

Background:

• Glioblastoma (GBM) is an aggressive brain tumor with poor prognosis.
• Conventional therapies face challenges due to infiltrative growth and the blood-brain barrier (BBB).
• Drug delivery to the brain is hindered by the impermeable BBB.

Purpose of the Study:

• To develop a stimuli-responsive nanoplatform for targeted glioblastoma drug delivery.
• To engineer elastin-like polypeptide (ELP)-based nanoparticles for enhanced drug encapsulation and controlled release.
• To evaluate the efficacy of ELP-nanoparticles in overcoming the BBB and treating glioblastoma in vivo.

Main Methods:

• Engineered chimeric polypeptide-doxorubicin conjugates (L-CP-DOX NPs) with varying ELP chain lengths.
• Selected L-CP1200-DOX NPs as the optimal formulation based on drug encapsulation and release properties.
• Utilized tumor-penetrating peptide LinTT1 for BBB traversal and mild hyperthermia for triggered drug release.
• Assessed nanoparticle accumulation, antitumor efficacy, and toxicity in orthotopic glioblastoma models.

Main Results:

• L-CP1200-DOX NPs demonstrated enhanced drug encapsulation and superior temperature-responsive release.
• The nanoparticles efficiently traversed the BBB and targeted tumor tissues when mediated by LinTT1.
• Mild hyperthermia induced ELP1200 phase transition, leading to tumor-specific doxorubicin release.
• In vivo studies showed enhanced tumor accumulation, significant antitumor efficacy, and reduced off-target toxicity.

Conclusions:

• ELP-based nanocarriers represent a versatile platform for thermally responsive brain tumor targeting.
• The developed nanoplatform shows translational promise for protein-based drug delivery systems in neuro-oncology.
• This approach offers a potential strategy to overcome BBB limitations and improve glioblastoma treatment outcomes.