Rationally integrating peptide-induced targeting and multimodal therapies in a dual-shell theranostic platform for orthotopic metastatic spinal tumors.

Metastatic tumors present great challenges in diagnosis and treatment. Herein, a proof-of-concept theranostic nanoplatform composed of an Au nanoparticle core and a double-shell of metal-organic framework (MOF) and mesoporous silica (MS) is developed for combating spinal metastasis of lung cancer in an orthotopic model. Two drugs, Alpelisib (BYL719) as an inhibitor and cisplatin as a chemotherapeutic drug, are separately loaded into the double-shell with high loading content. A targeting peptide called dYNH and indocyanine green (ICG) are conjugated onto the outmost MS layer for specifically targeting metastatic tumor cells and enhancing photothermal effect. The resultant Au@MOF@MS-ICG -dYNH-PAA (AMMD) shows enhanced cellular uptake on tumor cells and accumulation at metastatic spinal tumors, as evidenced by fluorescent and photoacoustic imaging. Benefiting from this ultra-high affinity to tumor cells and the photothermal effect of ICG, the dual-drug-loaded AMMD (BCAMMD) modified with ICG exhibits superior therapeutic efficacy on spinal tumors. More importantly, bone destruction, which frequently occurs in bone-related tumors, is effectively suppressed by BYL719 in BCAMMD. Hence, by rationally integrating multiple functions, including excellent targeting ability, dual-drug loading, photothermal therapy, and photoacoustic imaging, the developed all-in-one theranostic nanoplatform provides a useful paradigm of employing nanomedicine to treat metastatic spinal tumors efficiently.

Cloning, differential tissue expression of a novel hcApo gene, and its correlation with total carotenoid content in purple and white inner-shell color pearl mussel Hyriopsis cumingii.

As a molecular carrier and storage protein, apolipoprotein (Apo) mediates the intracellular uptake of lipids, proteins, vitamins and carotenoids. In this study, we identified a novel Apo gene, designated hcApo, from the freshwater pearl mussel Hyriopsis cumingii. The complete hcApo cDNA consists of 4104 nucleotides with an open reading frame encoding 1155 amino acid residues. The hcApo protein contains a conserved lipoprotein N-terminal domain (LPD-N) that is a characteristic of the large lipid transfer protein (LLTP) superfamily. The hcApo mRNA is constitutively expressed in a wide range of tissues with the highest expression level in the liver. Moreover, differential expression analysis revealed that the hcApo gene is more highly expressed in the liver, kidney, mantle and gill of purple line mussels compared to white line mussels. In situ hybridization investigations of the precise expression site of hcApo mRNA in the mantle showed that hcApo mRNA is specifically expressed in the outer epithelial cells of the middle fold and the inner epithelial cells of the outer fold of the mantle, as well as throughout the outer epithelium of the outer fold and ventral mantle. Another very important finding is that significantly positive correlation existed between the hcApo gene expression level and the total carotenoid content in purple line mussels. These findings may provide a better understanding of the roles of hcApo in the molecular mechanisms of shell formation and coloring of H. cumingii.