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Esterase-sensitive cleavable histone deacetylase inhibitor-coupled hyaluronic acid nanoparticles for boosting anticancer activities against lung adenocarcinoma

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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.

Graphical abstract: Esterase-sensitive cleavable histone deacetylase inhibitor-coupled hyaluronic acid nanoparticles for boosting anticancer activities against lung adenocarcinoma

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Publication details

The article was received on 09 Jun 2019, accepted on 12 Aug 2019 and first published on 13 Aug 2019


Article type: Paper
DOI: 10.1039/C9BM00895K
Biomater. Sci., 2019, Advance Article

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    Esterase-sensitive cleavable histone deacetylase inhibitor-coupled hyaluronic acid nanoparticles for boosting anticancer activities against lung adenocarcinoma

    S. Y. Lee, E. Hong, J. Y. Jeong, J. Cho, J. Seo, H. Ko and H. Cho, Biomater. Sci., 2019, Advance Article , DOI: 10.1039/C9BM00895K

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