During conventional chemotherapy for cancer, nonspecific drug distribution, which causes serious side effects in normal tissues, is a serious limitation. Thus, it is desirable to develop a tumor or intracellular microenvironment-responsive nanosystem for targeted and on-demand drug release. In the present study, we engineered an intelligent pH-activatable nanosystem, in which a gadolinium-doxorubicin-loaded nanoscale coordination polymer (Gd-Dox NCPs) was the core and hyaluronic acid was the targeting shell. Taking advantage of CD44 receptor-mediated recognition, the nanoparticles were internalized selectively into human cervical carcinoma (HeLa) cells, and trapped within acidic compartments where the fluorescence of Dox recovered, along with the acid dismantling of the Gd NCPs, allowing real-time monitoring of drug release. In vitro experiments also showed that the Gd NCPs present enhanced T1 signals after acid-triggered degradation, suggesting their potential use as contrast agents for magnetic resonance imaging. Such nanocarriers, which feature high biodegradation, selective targeting ability, and rapid response to stimulus, demonstrated enhanced therapeutic efficacy in targeted cancer cells and "turned on" T1 signals in vitro, showing great promise for diagnosis and treatment.
Drug resistance renders standard chemotherapy ineffective in the treatment of connective tissue growth factor (CTGF)-overexpressing breast cancer. By co-embedding the breast tumor cell-penetrating peptide (PEGA-pVEC) and hyaluronic acid (HA) as a targeting media, novel cascaded targeting nanoparticles (HACT NPs) were created on a rattle mesoporous silica (rmSiO2) scaffold for the pinpoint delivery of siRNAs along with an anticancer drug, aiming at overcoming the drug resistance of CTGF-overexpressing breast cancer in vivo. The targeting nanoparticles selectively accumulated in the vasculature under the guidance of the PEGA-pVEC peptide, cascaded by receptor-mediated endocytosis with the aid of another targeting agent, HA, presenting a greater in vivo tumor targeting ability than single targeting ligand vectors. In addition, an HA shell prevented the leakage of therapeutic drugs during the cargo transport process, until the hyaluronidase (HAase)-triggered degradation upon lysosomes entering, guaranteeing a controllable drug release inside the target cells. When the protective shell disintegrates, the released siRNA took charge to silence the gene associated with drug resistance, CTGF, thus facilitating doxorubicin-induced apoptosis. The cascaded targeting media (PEGA-pVEC and HA) advances precision-guided therapy in vivo, while the encapsulation of siRNAs into a chemotherapy drug delivery system provides an efficient strategy for the treatment of drug resistance cancers.

A novel biosensor based on a myoglobin/gold nanoparticles/carbon spheres (Mb-AuNPs-CNs) 3-D architecture bioconjunction has been fabricated for the determination of hydrogen peroxide (H2O2). Cyclic voltammetry (CV), Fourier transform infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM) were used to characterize the bioconjunction of the AuNPs-CNs with Mb. Experimental results demonstrate that the AuNPs-CNs hybrid material is more effective in facilitating electron transfer of the immobilized enzyme than CNs alone, which can be attributed to the unique nanostructure and larger surface area of the bioconjunction. The biosensor displayed good performance for the detection of H2O2 with a wide linear range from 0.28 μmol/L to 116.5 μmol/L and a detection limit of 0.12 μmol/L. The Michaelis-Menten constant KMapp value was estimated to be 0.3 mmol/L. The resulting biosensor exhibited fast amperometric response, and good stability, reproducibility, and selectivity to H2O2.