pH ‐Responsive PEG‐Shedding and Targeting Peptide‐Modified Nanoparticles for Dual‐Delivery of Irinotecan and microRNA to Enhance Tumor‐Specific Therapy

Collectively, successful delivery of miR and chemotherapy by pH ‐responsive targeting nanoparticles modulates β‐catenin/multiple drug resistance/apoptosis/metastasis pathways and induces cancer cell death, mainly via apoptosis. These pH‐sensitive targeting nanoparticles carrying chemotherapy and gene therapeutics remarkably enhance anticancer efficacy in tumor‐bearing mice. Thus, these nanoparticles may provide a potential regimen for effective treatment of colorectal cancer. AbstractIrinotecan is one of the main chemotherapeutic agents for colorectal cancer (CRC). MicroRNA ‐200 (miR‐200) has been reported to inhibit metastasis in cancer cells. Herein, pH‐sensitive and peptide‐modified liposomes and solid lipid nanoparticles (SLN) are designed for encapsulation of irinotecan and miR‐200, respectively. These peptides include one cell‐penetrating peptide, one ligand targeted to tumor neovasculature undergoing angiogenesis, and one mitochondria‐targeting peptide. The peptide‐modified nanoparticles are further coated with a pH‐sensitive PEG‐lipid derivative with an imine bond. These specially‐designed nanoparticles exhibit pH‐responsive releas e, internalization, and intracellular distribution in acidic pH of colon cancer HCT116 cells. These nanoparticles display low toxicity to blood and noncancerous intestinal cells. Delivery of miR‐200 by SLN further increases the cytotoxicity of irinotecan‐loaded liposomes against CRC cells by tri ggering ...
Source: Small - Category: Nanotechnology Authors: Tags: Full Paper Source Type: research