Esterase-sensitive cleavable histone deacetylase inhibitor-coupled hyaluronic acid nanoparticles for boosting anticancer activities against lung adenocarcinoma. (27th August 2019)

• Record Type: Journal Article
• Authors: Lee, Song Yi; Hong, Eun-Hye; Jeong, Jae Young; Cho, Jaewon; Seo, Ji-Hye; Ko, Hyun-Jeong; Cho, Hyun-Jong
• Is Part Of: Biomaterials science. Volume 7:Number 11(2019)
• Page Start: 4624
• Page End: 4635
• Publication Date: 2019-08-27
• Subjects: Biomedical materials -- Periodicals; 610.28
• DOI: 10.1039/c9bm00895k
• Languages: English
• ISSNs: 2047-4830

Abstract

Abstract : 4-Phenylbutyric acid (PBA)-installed hyaluronic acid (HA)-based nanoparticles (NPs) were developed for amplifying the anticancer potential of curcumin (CUR) for lung cancer therapy. Abstract : 4-Phenylbutyric acid (PBA)-installed hyaluronic acid (HA)-based nanoparticles (NPs) were developed for amplifying the anticancer potential of curcumin (CUR) for lung cancer therapy. PBA was introduced to the HA backbone as a hydrophobic segment of a nanoassembled structure and as a histone deacetylase (HDAC) inhibitor for cancer therapy. PBA was released from the HA–PBA conjugate (HAPBA) via an esterase-responsive cleavage of ester bonds in cancer cells and may affect the dissociation of NP structure. CUR-entrapped HAPBA-based NPs, with 265 nm hydrodynamic size, unimodal size distribution, negative zeta potential, and sustained drug release, were fabricated. Co-treatment of A549 cells by PBA and CUR elevated the antiproliferation efficiency compared with CUR-treatment. CUR-loaded HAPBA NPs also exhibited a significantly lower IC50 value compared with the CUR and HAPBA10 + CUR groups ( p < 0.05). Cy5.5-labeled HAPBA NPs containing CUR group displayed higher accumulation in tumor tissue and less distribution in liver and spleen after intravenous injection compared with the Cy5.5-injected group in A549 tumor-bearing mouse model. Multiple dosing of CUR-loaded HAPBA NPs in A549 tumor-bearing mouse model exhibited efficient tumor growth suppression and apoptosis-inducing effects. CD44 receptor targeting and HDAC inhibiting HAPBA NPs can be used to boost the anticancer potentials of drug cargo for the therapy of CD44 receptor-expressed cancers.