Matrix metalloproteinase-directed precise targeting and smart drug delivery of biodegradable gold nanodandelions as CT imaging guided anticancer therapy

Systemic adverse effects and poor accumulation at tumor sites constitute important limitations of current chemotherapy in the battle against the majority of cancers. Even though utilization of nanoparticle technology is the preferred treatment modality for improving drug delivery efficiency, achieving controlled drug release and image-guided therapy still pose challenges. In this paper, we developed a tumor microenvironment-responsive gold nanodandelions encapsulating doxorubicin (GNDs@gelatin/DOX) for tumor-targeted imaging and drug delivery. High surface-area GNDs were prepared through a gelatin-mediated process which showed great DOX-loading efficiency. Specifically, GNDs@gelatin/DOX is cleavable by gelatinase (e.g., matrix metalloproteinases −2 and −9) to release the cancer therapeutic agent and aggregate in tissues where these enzymes are upregulated. We demonstrate that GNDs@gelatin/DOX accumulated preferentially in matrix metalloproteinases-2/-9 (MMP-2/-9) overexpressed tumor after intravenous injection, which is useful for computed tomography (CT) imaging-guided chemotherapeutics. Intriguingly, GNDs@gelatin/DOX exhibited the capacity to control and prolong Dox release induced suppression of tumor growth and less cardiotoxicity compared with conventional doxorubicin. In addition, our results show that the alternation of tissue inhibitors of metalloproteinases (TIMP) can attenuate MMP activity, and thus reduce the sensitivity of cancer cells to chemotherapeutics. It is noteworthy that in vivo CT imaging and subsequent inductively coupled plasma-mass spectroscopy (ICP-MS) of harvested tissues revealed that GNDs was found to transport into the gastrointestinal tract and substantial elimination from the mice with prolonged time. In aggregate, GNDs@gelatin/DOX is a highly promising chemotheranostic agent for clinical translation.