Multifunctional fluorescent mesoporous carbon nanoprobe for MMP-2-activated cancer cell imaging and targeted photothermal therapy.

The integration of cancer imaging with therapy in a simple system is warranted for precise cancer therapy. In this study, carboxyl-functionalized mesoporous carbon nanospheres (MCN) which are efficient photothermal agents and excellent fluorescence quenchers, were used for cancer cell imaging and selective photothermal therapy (PTT) applications. Using MCN, a matrix metalloproteinase-2 (MMP-2)- responsive theranostic nanoprobe was generated by functionalizing an MMP-2-specific fluorescent-labeled PLGVR sequence on the surface of MCN. The nanoprobe not only can be used to detect MMP-2 with a low detection limit of 0.3 pg mL-1, but also can achieve the sensitive intracellular MMP-2 imaging in living cells, validating the differentiation of cancer cells from healthy cells based on the recovered fluorescence intensity. More importantly, selective cancer PTT was achieved using MMP-2-triggered cancer cell imaging. Our in vitro studies showed that by regulating the power density and irradiation time, the nanoprobe can effectively kill cancer cells via PTT. Our strategy opens new avenues for precision medicine, especially phototherapy.

Hyaluronic acid coated mesoporous carbon-copper peroxide for H2O2 self-supplying and near-infrared responsive multi-mode breast cancer oncotherapy.

It is challenging to develop the synergistic intelligent therapeutic nanoplatform to cure cancer. In the present study, a novel nanotherapeutic platform was constructed for H2O2 self-supplying and multimodal breast cancer therapy. In which, copper peroxide nanoparticles (CP NPs) were adsorbed on the surface of mesoporous carbon nanospheres (MCN) through electrostatic attraction, followed by loading doxorubicin (DOX) into the nanocomposite (MCN-CP) and coating hyaluronic acid (HA) on the surface, the DOX/MCN-CP-HA nanoplatform was obtained. In the system, the MCN not only possessed a high DOX loading capacity, but produced excellent photothermal therapy (PTT) effect. Importantly, the ultra-small CP NPs as the Fenton agent not only could selectively self-supplying H2O2 in acidic condition, but simultaneously release Cu2+ to catalyze the production of ·OH in the presence of H2O2. Meantime, the resulting Cu2+ possessed GSH-elimination property, which afforded enhanced chemodynamic therapy (CDT). Furthermore, the outer layer HA targeted to CD44 and achieved breast cancer cell targeting. The elevated temperature from PTT and acidic tumor microenvironment accelerated the release of DOX, which enabled DOX/MCN-CP-HA as an intelligent CDT-PTT-chemotherapy synergistic nanoplatform. In vitro and in vivo pharmacodynamic evaluations confirmed the potential of the nanoplatform for CDT-PTT-chemotherapy synergistic oncotherapy of breast cancer.

Dual stimulus-responsive core-satellite SERS nanoprobes for reactive oxygen species sensing during autophagy.

As one kind of reactive oxygen species, hydrogen peroxide (H2O2) participated in various cellular biological processes including cell differentiation and inflammation responses. Abnormal H2O2 level is closely related to cancer and other diseases. Highly sensitive detection and monitoring H2O2 are of great importance for understanding the roles of H2O2 in cellular dynamic events. Herein, a novel dual stimulus-responsive core-satellite surface-enhanced Raman scattering (SERS) nanoprobe engineered with manganese dioxide (MnO2) and silver nanoparticles (Ag NPs) was constructed for sensitive H2O2 detection. The sensing strategy is based on the target-triggered degradation both of the "core" and "satellite". In this system, the MnO2 core not only could be used as solid supporter to generate "hot spots" that can induce strong SERS signals, but also acted as the responsive unit for H2O2 sensing together with Ag NPs. A good linear relationship in the range from 1 to 100 µM and limit of detection of 7.44 µM were obtained. Moreover, the nanosensor possessed good repeatability. Based on this strategy, the sensitive detection of cellular H2O2 was achieved. Furthermore, the SERS-based H2O2 monitoring during the starvation-induced autophagy was realized by the developed nanoprobes. Our study provides a new way for sensitive H2O2 detection and opens a new avenue for sensing and detection of other biomolecules.

Synergistic H2O2 self-supplying and NIR-responsive drug delivery nanoplatform for chemodynamic-photothermal-chemotherapy.

Developing effectively synergistic multi-mode drug delivery nanoplatform for cancer treatment is of great significance but still challenging. Here, we construct core-shell (CaO2@Au nanoshells) nanoparticles coated with doxorubicin-loaded hyaluronic acid. The developed platform can be used as synergistic H2O2 self-supplying and near-infrared-enhanced reactive oxygen species producer for chemodynamic-photothermal-chemotherapy multi-mode drug delivery. In this platform, the CaO2 possesses a high capacity of self-supplying H2O2 in acidic conditions, while retains desired stability under physiological conditions. The in-situ deposited Au nanoshells not only provide a remarkable photothermal therapy, but function as peroxidase mimics to catalyze H2O2 to produce hydroxyl radical to afford highly efficient chemodynamic therapy. Furthermore, the outer layer hyaluronic acid can load doxorubicin and target overexpressed receptor CD44 of cancer cell, meanwhile, trigger release of DOX in photothermal condition and acidic tumor microenvironment. The results of in vitro cell viability and in vivo tumor inhibition indicate that the developed synergistic nanoplatform hold the potential as an efficient strategy for chemodynamic-photothermal-chemotherapy combination therapy of cancer.