Anti-CD44 monoclonal antibody, clone ZLJY448.9 [FITC]

Multidrug resistance (MDR) is a serious challenge in chemotherapy and also a major threat to breast cancer treatment. As an intracellular energy factory, mitochondria provide energy for drug efflux and are deeply involved in multidrug resistance. Mitochondrial targeted delivery of doxorubicin can overcome multidrug resistance by disrupting mitochondrial function. By incorporating a reactive oxygen species (ROS)-responsive hydrophobic group into the backbone structure of hyaluronic acid - a natural ligand for the highly expressed CD44 receptor on tumor surfaces, a novel ROS-responsive and CD44-targeting nano-carriers was constructed. In this study, mitochondria-targeted triphenylphosphine modified-doxorubicin (TPP-DOX) and amphipathic ROS-responsive hyaluronic acid derivatives (HA-PBPE) were synthesized and confirmed by(1)H NMR. The nanocarriers TPP-DOX @ HA-PBPE was prepared in a regular shape and particle size of approximately 200 nm. Compared to free DOX, its antitumor activity in vitro and tumor passive targeting in vivo has been enhanced. The ROS-responsive TPP-DOX@HA-PBPE nanocarriers system provide a promising strategy for the reverse of MDR and efficient delivery of doxorubicin derivatives into drug-resistant cancer cells.

In search of facile yet efficient therapeutic and imaging nanoagents for cancer treatment, versatile self-reporting gold nanourchins (AuNUs) featuring synergic chemo-photothermal therapies and multimodal imaging are fabricated. AuNUs are synthesized using a surfactant-free approach, and then functionalized with a Raman reporter 4-mercaptophenylboronic acid (4-MPBA) and dopamine to form adenosine triphosphate (ATP)-cleavable boronate ester bonds prior to further immobilization with hyaluronic acid (HA) for cancer targeting. Controlled release of an anticancer drug, doxorubicin (DOX), loaded in the interstices of AuNUs, is achieved upon exposure to the overproduced hyaluronidase (HAase) in a tumor microenvironment. The spiny exterior of AuNUs enables their optophysical conversion of near-infrared (NIR) light (808 nm) to heat for photothermal therapy and IR imaging. The surface enhanced Raman scattering (SERS) of AuNUs also allows sensitive and reliable Raman mapping of their cellular uptake in vitro, and intratumoral accumulation in vivo, complementary to conventional photoacoustic imaging (PAI). With a demonstrated ability to eradicate tumors and enable multimodal imaging, AuNUs exemplify ongoing efforts in design and utility of multifunctional nanoplatforms.