Peptide-Based Nanoparticles Mimic Fibrillogenesis of Laminin in Tumor Vessels for Precise Embolization

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.

Peptide-Based AIEgens: From Molecular Design, Stimuli Responsiveness to Biomedical Application

“…The method of changing the shape of AIE peptide-based nanomaterials through pH response to achieve tumor suppression provides new ideas for tumor treatment. 35 targeting the VEGFR2 receptor over-expressed on the surface of tumor cell membranes to release drugs more efficiently and achieve the therapeutic effects. The successful design of responsive materials has important implications for targeted imaging diagnosis, detections, and specific cancer treatments.…”

Emerging Biomaterials‐Based Strategies for Inhibiting Vasculature Function in Cancer Therapy

“…These structures entangled and caused rapid occlusion of tumor blood vessels within 4 h after intravenous injection and retained for more than 48 h, indicating in precise and long‐term blockage. [ 74 ]…”

Smart Nanogatekeepers for Tumor Theranostics

“…The rapid proliferation and growth of tumor cells rely heavily on the nutritional supply from tumor vessels. [24] In the clinic, tumor vessel-based tumor therapy is generally categorized into vessel occlusion strategy, [25] vascular disrupting agents (VDAs) [20] and angiogenesis inhibitors, [26] which selectively target vascular endothelial cells or destroy blood vessel structure, thereby inducing local coagulation reactions and specific blockage of the nutritional supply in tumor tissues.…”

“…Wang and co-workers first constructed a laminin mimic peptide (LMMP) composed of a hydrogen-bonding fibrillation sequence (KLVFF), pH-responsive histidine sequence (His 6 ), microthrombus targeting peptide (CREKA), hydrophilic oligo ethylene glycol, and a hydrophobic bis-pyrene (BP) motif, and then utilized the constructed LMMP to fabricate pH-and microthrombus dual-responsive LMMP-based nanoparticles (LMMP NPs) through a rapid precipitation method. [25] After systemic intravenous administration, the prepared LMMP NPs specifically bind to the microthrombus on the inner tumor vessel wall, while the acidic vessel environment (around pH 6.5) protonates the His 6 segment and then breaks the intrinsic hydrophilichydrophobic balance of LMMP NPs. This successfully transforms the NPs to fibrous networks during contact with microthrombi in tumorous blood vessels (Figure 2A).…”