Peptide-Based Pegylated Polyurethane Nanoparticles for Paclitaxel Delivery in Hela Cancer Cells: The Art of the Architecture Design in Nanocarriers Publisher

Summary: A study found new pH-sensitive nanocarriers improve cancer drug delivery, reducing resistance. #CancerResearch #DrugDelivery

Rafiemanzelat F^{1, 2} ; Tafazoli S¹ ; Hairi AA³ ; Varshosaz J⁴ ; Mirian M⁵ ; Khodarahmi G³ ; Hassanzadeh F³ ; Rostami M⁶
Source: Polymer Bulletin Published:2023

Abstract

Designing new drug delivery systems (DDSs) with appropriate performance and tunable release properties for targeted cancer treatment is still a topic of interest. Waterborne polyurethanes (WPU)s are versatile materials for this purpose. However, they need to hybrid with natural polymers to improve their biodegradability. New pH-sensitive folate-targeted peptide-based PEGylated nanocarriers utilizing biodegradable WPUs with tunable bioactivity were designed for paclitaxel (PTX) delivery in this work. Enjoying different structural designs of WPUs through changing block arrangement and synthesis strategies, we adjusted degradation and different aggregation morphologies of water-dispersed nanocarriers comprising micelles, nanoparticles (NPs), or core–shell NPs. The effectiveness of these structural designs was studied completely in vitro. Their hydrodynamic size and zeta potentials range 148–470 nm and − 8 to − 23.5 mV, respectively; two formulas with micellar and core–shell nanoparticular characteristics were selected as the best candidates (PEU2-PEG-FAend micelles with a hydrodynamic size of 251 nm, ZP about − 16.1 mV, and CMC value of 0.024 mg/mL; PEU2@PEG-FA core–shell NPs with a hydrodynamic size of 153 nm and ZP of about − 23.5 mV). Benefiting from the precise design and sequencing of structural segments and the bioactivity of Ser and LCP, these synthetic nanocarriers exhibited reasonable biodegradation rate, cytocompatibility, and blood compatibility. Core–shell NPs showed the highest loading capacity for PTX (LC% was 44) and the most controlled release among all studied nanostructures. In vitro release studies showed that the drug-loaded nanocarriers (PEU2-PEG-FAend micelles and PEU2@PEG-FA core–shell NPs) have a sustained release feature at acidic pH of 5.5 to about 100% within 72 h. The IC50s of nanomicelles (49.5 μg/mL) and core–shell NPs (32.5 μg/mL) were lower than free PTX (69.5 μg/mL). Finally, flow cytometry results approved better internalization of targeted micelles (99.6% versus 87.6%) and core–shell NPs (100% versus 73.5%) than non-targeted ones into HeLa cells via endocytosis. These nanocarriers would be promising targeted anticancer DDS to guarantee adequate drug concentration to kill the cancer cells and avoid multi-drug resistance. © 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.