Transferrin receptors/magnetic resonance dual-targeted nanoplatform for precise chemo-photodynamic synergistic cancer therapy.

Various drug delivery strategies to improve cancer therapeutic efficacy have been actively investigated. One major challenge is to improve the targeting ability. Here elaborately designed nanocarriers (NCs) named as Tf-5-ALA-PTX-NCs are demonstrated to address this problem. In this nanostructure, paclitaxel (PTX) and 5-aminolevulinic acid (5-ALA) were co-encapsulated within magnetic nanocarriers to achieve synergistic chemotherapy and photodynamic therapy, while transferrin (Tf) was conjugated with modified copolymer Pluronic P123 and embedded in the surface of the nanocarriers, which endows nanocarriers with Tf targeting and magnetic targeting to enhance the anti-tumor outcome. Results demonstrated that Tf-5-ALA-PTX-NCs significantly enhanced the targeting drug delivery to MCF-7 cells and synergistically induced apoptosis and death of MCF-7 cells in vitro and highly efficient tumor ablation in vivo. Intriguingly, Tf-5-ALA-PTX-NCs have a controllable "on/off" switch to enhance the drug release. The dual-targeted nanocarriers would be a promising versatile anti-tumor drug delivery and imaging-guided cancer chemo-photodynamic synchronization therapy strategy.

Different Expressions of HIF-1α and Metabolism in Brain and Major Visceral Organs of Acute Hypoxic Mice.

Hypoxia is associated with clinical diseases. Extreme hypoxia leads to multiple organs failure. However, the different effects of hypoxia on brain and visceral organs still need to be clarified, and moreover, characteristics in vulnerable organs suffering from hypoxia remain elusive. In the present study, we first aimed to figure out the hypoxic sensitivity of organs. Adult male mice were exposed to 6% O2 or 8% O2 for 6 h. Control mice were raised under normoxic conditions. In vivo and in vitro imaging of anti-HIF-1α-NMs-cy5.5 nanocomposites showed that the expression level of hypoxia-inducible factor (HIF-1α) was the highest in the liver, followed by kidney and brain. HIF-1α was detected in the hepatocytes of liver, distal convoluted tubules of kidney and neurons of cerebral cortex. The liver, kidney and brain showed distinct metabolic profiles but an identical change in glutamate. Compared with kidney and brain, the liver had more characteristic metabolites and more disturbed metabolic pathways related to glutaminolysis and glycolysis. The level of O-phosphocholine, GTP, NAD and aspartate were upregulated in hypoxic mice brain, which displayed significant positive correlations with the locomotor activity in control mice, but not in hypoxic mice with impaired locomotor activities. Taken together, the liver, kidney and brain are the three main organs of the body that are strongly respond to acute hypoxia, and the liver exhibited the highest hypoxic sensitivity. The metabolic disorders appear to underlie the physiological function changes.