Study on the effectiveness of ligand reversible shielding strategy in targeted delivery and tumor therapy

Hu, ZP (Hu, Zhenpeng)^[ 1 ] ; Li, XM (Li, Xiaomin)^[ 1 ] ; Yuan, M (Yuan, Ming)^[ 1 ] ; Wang, XY (Wang, Xinyu)^[ 1 ] ; Zhang, YP (Zhang, Yapei)^[ 1 ] ; Wang, W (Wang, Wei)^[ 1 ] ; Yuan, Z (Yuan, Zhi)^[ 1,2 ]

ACTA BIOMATERIALIA, 2019, 83: 349-358

DOI: 10.1016/j.actbio.2018.11.021

Abstract

We previously proved the superiority of the ligand reversible shielding strategy based on the pH responsive self-assembly/disassembly of gold nanoparticles through computed tomography imaging in vivo. Herein, the practicality of this strategy in tumor therapy was investigated by a ligand reversible shielding system based on a temperature-responsive polymer. The ligand biotin, cisplatin-loaded chain poly(acrylic acid)-Pt, and the shielding segment thermo-sensitive poly(N-isopropylacrylamide-co-acryla mide) (P(NIPAAm-co-AAm)) were co-modified onto the surface of gold nanostars. In the blood circulation (37 degrees C), the ligand was shielded by the extension of P(NIPAAm-co-AAm), whose lower critical solution temperature (LCST) is approximately 39 degrees C. After the nanoparticles accumulate at the tumor site by the enhanced permeability and retention (EPR) effect, the heat generated from gold nanostars upon near-infrared light irradiation would trigger the contraction of P(NIPAAm-co-AAm), thus deshielding the ligand for enhanced tumor cellular uptake. Owing to the reversible extension-contraction transformation change of P(NIPAAm-co-AAm), the reversible shielding effect on the ligand could be accomplished even if the nanoparticles return to the blood circulation. The results indicated that the system could extend blood circulation (1.6-fold at 24 h), reduce immune system clearance (28% lower), and enhance tumor accumulation (37% higher) effectively compared with the irreversible ligand shielding system by analysis of platinum. This strategy showed significantly superior tumor inhibition (11% higher) than the irreversible system. All these results make clear that the ligand reversible shielding strategy is effective and offers important references for the design of nanomaterials for improving tumor accumulation. (C) 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.