The generation of dendrimers is a powerful tool in the control of the size and biodistribution of polyion complexes (PIC). Using a combinatorial screening of six dendrimers (18-243 terminal groups) and five oppositely charged PEGylated copolymers, a dendrimer-to-PIC hierarchical transfer of structural information was revealed with PIC diameters that increased from 80 to 500 nm on decreasing the dendrimer generation. This rise in size, which was also accompanied by a micelle-to-vesicle transition, is interpreted according to a cone- to rod-shaped progression in the architecture of the unit PIC (uPIC). This precise size tuning enabled dendritic PICs to act as nanorulers for controlled biodistribution. Overall, a domino-like control of the size and biological properties of PIC that is not attainable with linear polymers is feasible through dendrimer generation.
Nanomaterials with very low atomicity deserve consideration as potential pharmacological agents owing to their very small size and to their properties that can be precisely tuned with minor modifications to their size. Here, it is shown that silver clusters of three atoms (Ag -AQCs)-developed by an ad hoc method-augment chromatin accessibility. This effect only occurs during DNA replication. Coadministration of Ag -AQCs increases the cytotoxic effect of DNA-acting drugs on human lung carcinoma cells. In mice with orthotopic lung tumors, the coadministration of Ag -AQCs increases the amount of cisplatin (CDDP) bound to the tumor DNA by fivefold without modifying CDDP levels in normal tissues. As a result, CDDP coadministered with Ag -AQCs more strongly reduces the tumor burden. Evidence of the significance of targeting chromatin compaction to increase the therapeutic index of chemotherapy is now provided.
Funding:Highlights:• The sustained delivery of BMP-7 enhances the chondrogenic activity of TGF-β3.• BMP-7 and TGF-β3 can be entrapped in polymers matrices as PEG-heparin complexes.• Scaffolds delivering TGF-β3 and BMP-7 drive the chondrogenesis of cell progenitors.
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