Esterase-sensitive cleavable histone deacetylase inhibitor-coupled hyaluronic acid nanoparticles for boosting anticancer activities against lung adenocarcinoma
4-Phenylbutyric acid (PBA)-installed hyaluronic acid (HA)-based nanoparticles (NPs) for amplifying anticancer potentials of curcumin (CUR) were developed for the therapy of lung cancer. PBA was introduced to HA backbone as a hydrophobic segment of nanoassembly structure and a histone deacetylase (HDAC) inhibitor for cancer therapy. PBA was released from HA-PBA conjugate (HAPBA) via an esterase-responsive cleavage of ester bond in cancer cells and it may affect the dissociation of NP’s 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 PBA and CUR to A549 cells elevated antiproliferation efficiencies compared with CUR-treatment. CUR-loaded HAPBA NPs also exhibited significantly lower IC50 value compared with 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 compared with Cy5.5-injected group after intravenous injection in A549 tumor-bearing mouse model. Multiple dosing of CUR-loaded HAPBA NPs in A549 tumor-bearing mouse exhibited efficient tumor growth suppression and apoptosis inducing effects. CD44 receptor targeting and HDAC inhibiting HAPBA NPs can be used for boosting anticancer potentials of drug cargo for the therapy of CD44 receptor-expressed cancers.