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Peptide-Based Nanoparticles Mimic Fibrillogenesis of Laminin in Tumor Vessels for Precise Embolization
Kuo Zhang1,2, Pei-Pei Yang2, Ping-Ping He2
1Department of Materials Physics and Chemistry, School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083, China.
Abstract:
Cancer therapeutic strategies based on angiogenesis attract great attention from fundamental and clinical research. Blocking oxygen and nutrition supply to tumor cells could inhibit the growth of tumors based on occlusion of blood vessels in the tumor. Herein, we report a dual-responsive peptide-based nanoparticle, mimicking the laminin fibrillogenesis specifically and highly efficiently in tumor vessels, resulting in the blockage of tumor vessels and the growth inhibition of tumors. The laminin mimic peptide (LMMP) is designed with a fibrillation sequence, a pH-responsive sequence, and a targeting sequence. The LMMP in nanoformulations is delivered to blood vessels in the tumors, where the microenvironment (pH and microthrombus) enable LMMP to process laminin fibrillogenesis, constructing fibrous networks. The laminin-like fibrous networks capture red blood cells etc., forming occlusion specifically in the tumor blood vessels to inhibit the growth of the tumor.
Insights
Researchers developed a dual-responsive peptide nanoparticle that mimics laminin to block tumor blood vessels. This novel approach effectively inhibits tumor growth by cutting off oxygen and nutrient supply.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Angiogenesis is a key target for cancer therapeutics, aiming to inhibit tumor growth by restricting blood supply.
- Current strategies focus on blocking oxygen and nutrient delivery to tumor cells via blood vessel occlusion.
Purpose of the Study:
- To develop a novel peptide-based nanoparticle that mimics natural laminin fibrillogenesis.
- To achieve specific and efficient blockage of tumor blood vessels for cancer treatment.
Main Methods:
- Design of a laminin mimic peptide (LMMP) with fibrillation, pH-responsive, and targeting sequences.
- Formulation of LMMP into nanoformulations for targeted delivery to tumor vasculature.
- Exploitation of the tumor microenvironment (pH, microthrombus) to trigger LMMP-induced fibrillogenesis.
Main Results:
- LMMP nanoformulations successfully mimicked laminin fibrillogenesis in tumor vessels.
- Constructed fibrous networks led to specific occlusion of tumor blood vessels.
- Tumor growth inhibition was observed due to the vascular blockage.
Conclusions:
- Dual-responsive peptide nanoparticles offer a promising strategy for cancer therapy by targeting tumor angiogenesis.
- Mimicking natural processes like laminin fibrillogenesis can lead to effective and specific therapeutic interventions.
- This approach provides a novel method for inhibiting tumor growth through vascular occlusion.
