A convenient method was reported to control the topological structure of copolyphosphates by adjusting the pendant group of cyclic phosphate monomers (CPMs) in the ring-opening polymerization (ROP), including linear block, star block, and hyperbranched multiarm structure. Linear block copolyphosphate (PEP-b-PIPP) was prepared by a two-step ROP procedure of CPMs with different pedant groups, i.e., monofunctional propargyl alcohol first initiated the ROP of the CPM with ethyl and then the CPM with isopropyl in turn. Similarly, star block copolyphosphate (SPEP-b-PIPP) was also synthesized when the monofunctional propargyl alcohol was replaced by a trifunctional trimethylolpropane. When the pendant group of CPM was changed into 2-hydroxyethyl, hyperbranched polyphosphate (HPHEP) was obtained first through the self-condensing ring-opening polymerization (SCROP) of such CPM, and then the terminal hydroxyls of HPHEP further initiated the ROP of CPM with ethyl to produce hyperbranched multiarm copolyphosphate (HPHEP-star-PEP). The resulting copolyphosphates were characterized by NMR, GPC, FTIR, and DSC techniques in detail, and the results confirmed their topological structures. Moreover, methyltetrazolium assay and AO/EB double staining methods indicated that all copolyphosphates with different topological structures had excellent biocompatibility against NIH 3T3 cells and would be applied as novel biomedical materials.
Amphiphilic block copolyphosphates (PEP-b-PIPPs) are synthesized by two-step ROP of cyclic phosphate monomers with different pedant groups. They can spontaneously self-assemble into approximately spherical micelles ranging in size between 89 and 198 nm in water. A typical hydrophobic anti-cancer drug DOX is encapsulated into the micelles. The release rate of DOX slows down with increasing hydrophobic block length of PIPP. DOX-loaded micelles are investigated for the proliferation inhibition of Hela cells and the DOX dose required for 50% cellular growth inhibition is found to be 0.8 µg mL(-1). It is demonstrated that PEP-b-PIPP micelles can be used as a safe and promising drug delivery system.
Background: It is well-established that serum testosterone in men decreases with age, yet the underlying mechanism of this change remains elusive.Methods: The expression patterns of Fancd2 opposite-strand (Fancd2os) in BALB/c male mice and testicular tissue derived cell lines (GC-1, GC-2, TM3, and TM4) were assessed using real-time polymerase chain reaction (RT-PCR), Western blot and immunofluorescence. The Fancd2os-overexpressing or knockdown TM3 cells were constructed by infecting them with lentivirus particles and were used to evaluated the function of Fancd2os. The testosterone production was measured using enzyme linked immunosorbent assay (ELISA) and the steroidogenic enzymes such as steroidogenic acute regulatory protein (StAR), P450 cholesterol side-chain cleavage (P450scc), and 3β-hydroxysteroid dehydrogenase (3β-HSD) were analysed using RT-PCR. The apoptosis of TM3 cells induced by ultraviolet light or testicular tissues was detected using flow cytometry, Western blot or dUTP-biotin nick end labeling (TUNEL) assays. Pearson correlation analysis was used to assess the correlation between the Fancd2os expression and TUNEL-positive staining in mouse testicular Leydig cells.Results: The Fancd2os protein was predominantly expressed in mouse testicular Leydig cells and its expression increased with age. Fancd2os overexpression inhibited testosterone levels in TM3 Leydig cells, whereas knockdown of <i>Fancd2os</i> elevated testosterone production. Fancd2os overexpression downregulated the levels of StAR, P450scc and 3β-HSD, while <i>Fancd2os</i> knockdown reversed this effect. Fancd2os overexpression promoted ultraviolet light-induced apoptosis of TM3 cells. In contrast, <i>Fancd2os</i> knockdown restrained apoptosis in TM3 cells. <i>In vivo</i> assays revealed that higher Fancd2os levels and mouse age were associated with increased apoptosis in Leydig cells and decreased serum testosterone levels. Pearson correlation analysis exhibited a strong positive correlation between the expression of Fancd2os and TUNEL-positive staining in mouse testicular Leydig cells.Conclusion: Our findings suggest that Fancd2os regulates testosterone synthesis via both steroidogenic enzymes and the apoptotic pathway.
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