We report functional gold nanoparticles (AuNPs) with a pH-sensitive γ-cyclodextrin (CD) cap. These particles include two chargeable CD molecules on their surface. CD with dopamine and amine (NH) groups (hereafter termed as dCD-NH) was anchored to the gold surface and then electrostatically complexed with the CD with 2,3-dimethylmaleic acid (DMA) and chlorin e6 (Ce6) (hereafter termed as cCD-DMA), producing an ionic complex consisting of dCD-NH and cCD-DMA. Under the acidic environment (pH 6.8) existing in most solid tumors, the ionic complex was destabilized because of the decoupling of DMA, resulting in the release of cCD (without DMA) from the AuNPs, resulting in extensive tumoral uptake of AuNPs with dCD-NH (because of their electrostatic attraction to tumor cells). This event resulted in a significant increase in the efficiency of cellular AuNP uptake and light-driven (AuNP-mediated photothermal and Ce6-mediated photodynamic) ablation of acidic solid tumors, suggesting marked potential for tumor therapy.

In this study, we designed and synthesized polysaccharidic nanogels comprising starch cross-linked with hyaluronic acid. These hyaluronated starch nanogels were prepared by cross-linking primary hydroxyl groups in polysaccharides (starch and hyaluronic acid) and epoxide groups in 1,4-butanediol diglycidyl ether (used as a cross-linking agent). The nanogels take advantage of hyaluronic acid as a specific ligand for CD44 receptors overexpressed on tumors and the hyaluronic acid/starch core as a compartment for the encapsulation of docetaxel (as model antitumor drug). Here, hyaluronic acid can be enzymatically degraded by tumor cell–specific enzyme (e.g. hyaluronidase-1), which could significantly accelerate docetaxel release from the nanogels. Our experimental results demonstrate that the nanogels promote the release of docetaxel content in the presence of hyaluronidase-1 enzyme. As a result, the nanogels selectively inhibited MCF-7 (with CD44 receptor and hyaluronidase-1 enzyme) tumor cell growth in vitro, suggesting their therapeutic potential for efficient tumor ablation.