pH-and reductive-responsive prodrug nanoparticles are constructed via a highly efficient strategy, polymerization-induced selfassembly(PISA). First, reversible addition-fragmentation chain transfer(RAFT) polymerizatio...pH-and reductive-responsive prodrug nanoparticles are constructed via a highly efficient strategy, polymerization-induced selfassembly(PISA). First, reversible addition-fragmentation chain transfer(RAFT) polymerization of 2-(diisopropylamino) ethyl methacrylate(DIPEMA) and camptothecin prodrug monomer(CPTM) using biocompatible poly(N-(2-hydroxypropyl) methacrylamide)(PHPMA-CPDB) as the macro RAFT agent is carried out, forming prodrug diblock copolymer PHPMA-P(DIPEMA-co-CPTM). Then, simultaneous fulfillment of polymerization, self-assembly, and drug encapsulation are achieved via RAFT dispersion polymerization of benzyl methacrylate(Bz MA) using the PHPMA-P(DIPEMA-co-CPTM) as the macro RAFT agent. The prodrug nanoparticles have three layers, the biocompatible shell(PHPMA), the drug-conjugated middle layer(P(DIPEMA-co-CPTM)) and the PBz MA core, and relatively high concentration(250 mg/g). The prodrug nanoparticles can respond to two stimuli(reductive and acidic conditions). Due to reductive microenvironment of cytosol, the cleavage of the conjugated camptothecin(CPT) within the prodrug nanoparticles could be effectively triggered. p H-Induced hydrophobic/hydrophilic transition of the PDIPEMA chains results in faster diffusion of GSH into the CPTM units, thus accelerated release of CPT is observed in mild acidic and reductive conditions. Cell viability assays show that the prodrug nanoparticles exhibit well performance of intracellular drug delivery and good anticancer activity.展开更多
Glycerol dialkyl glycerol tetraethers(GDGTs) in lake sediments are useful biomarkers for the continental paleoclimatic reconstruction. However, the environmental controls on the distribution of these compounds, in par...Glycerol dialkyl glycerol tetraethers(GDGTs) in lake sediments are useful biomarkers for the continental paleoclimatic reconstruction. However, the environmental controls on the distribution of these compounds, in particular the 6-methyl isomers of bacterial branched GDGTs(bGDGTs), in the lakes with contrasting pH, are still unknown, hindering their application for paleo-reconstructions. Here, we investigated the environmental impacts on the distribution of GDGTs in 17 alkaline lakes and 1 acid lake in China. It was found that the dissolved oxygen content in water column may have an impact on the distribution of archaeal isoprenoid GDGTs(iGDGTs) by causing the change in archaeal communities. The ratio of GDGT-0/crenarchaeol increases with decreasing oxygen content, indicating that the relative abundance of anaerobic methanogenic archaea or Miscellaneous Crenarchaeotic Group(MCG) vs. aerobic Thaumarchaeota is controlled by the oxygen content dissolved in water of these lakes. Thaumarchaeota are likely to contribute only a small proportion of iGDGTs in the relatively oxygen-depleted lakes, and thus TEX_(86) is not suitable for the reconstruction of the surface temperature of these lakes. The abundance ratio of iGDGTs to bGDGTs(R_(i/b)) appears to show no relationship with water pH in all the lakes, but exhibits a significant positive correlation with the water depth of the acid Lake Qinghai in Tengchong. As expected, the methylation degree of bGDGTs(MBT′) was found to correlate with both mean annual air temperature(MAT) and water pH, and the cyclization degree of bGDGTs(CBT) correlates only with water pH in these lakes. However, the MBT′_(5ME), an index to measure the methylation degree of 5-methyl bGDGTs, exhibits no relationship with MAT, whereas MBT′_(6ME), the methylation degree of 6-methyl bGDGTs, was found to correlate significantly with MAT. This is opposite to the situation observed in the global soils, pointing to a different adaptation of b GDGT-producing bacteria to environmental variables or different microbial sources of bGDGTs in these lakes. The relative abundance of 6- vs. 5-methyl bGDGTs is controlled by pH in these lakes, similar to that observed in worldwide soils. Hence, the isomer ratio(IR) of 6-methyl bGDGTs or CBT′ can be used as a proxy for water pH, although they might be influenced by other environmental factors including temperature in the lakes with a narrow range of pH.展开更多
基金supported by the National Key R&D Program of China (2017YFA0205601)the National Natural Science Foundation of China (51625305, 21704095, 21774113, 21525420)
文摘pH-and reductive-responsive prodrug nanoparticles are constructed via a highly efficient strategy, polymerization-induced selfassembly(PISA). First, reversible addition-fragmentation chain transfer(RAFT) polymerization of 2-(diisopropylamino) ethyl methacrylate(DIPEMA) and camptothecin prodrug monomer(CPTM) using biocompatible poly(N-(2-hydroxypropyl) methacrylamide)(PHPMA-CPDB) as the macro RAFT agent is carried out, forming prodrug diblock copolymer PHPMA-P(DIPEMA-co-CPTM). Then, simultaneous fulfillment of polymerization, self-assembly, and drug encapsulation are achieved via RAFT dispersion polymerization of benzyl methacrylate(Bz MA) using the PHPMA-P(DIPEMA-co-CPTM) as the macro RAFT agent. The prodrug nanoparticles have three layers, the biocompatible shell(PHPMA), the drug-conjugated middle layer(P(DIPEMA-co-CPTM)) and the PBz MA core, and relatively high concentration(250 mg/g). The prodrug nanoparticles can respond to two stimuli(reductive and acidic conditions). Due to reductive microenvironment of cytosol, the cleavage of the conjugated camptothecin(CPT) within the prodrug nanoparticles could be effectively triggered. p H-Induced hydrophobic/hydrophilic transition of the PDIPEMA chains results in faster diffusion of GSH into the CPTM units, thus accelerated release of CPT is observed in mild acidic and reductive conditions. Cell viability assays show that the prodrug nanoparticles exhibit well performance of intracellular drug delivery and good anticancer activity.
基金supported by the Fundamental Research Funds for the Central Universities (Grant No. CUGL150812)the National Natural Science Foundation of China (Grant No. 41330103)the Programme of Introducing Talents of Discipline to Universities Project (Grant No. B08030)
文摘Glycerol dialkyl glycerol tetraethers(GDGTs) in lake sediments are useful biomarkers for the continental paleoclimatic reconstruction. However, the environmental controls on the distribution of these compounds, in particular the 6-methyl isomers of bacterial branched GDGTs(bGDGTs), in the lakes with contrasting pH, are still unknown, hindering their application for paleo-reconstructions. Here, we investigated the environmental impacts on the distribution of GDGTs in 17 alkaline lakes and 1 acid lake in China. It was found that the dissolved oxygen content in water column may have an impact on the distribution of archaeal isoprenoid GDGTs(iGDGTs) by causing the change in archaeal communities. The ratio of GDGT-0/crenarchaeol increases with decreasing oxygen content, indicating that the relative abundance of anaerobic methanogenic archaea or Miscellaneous Crenarchaeotic Group(MCG) vs. aerobic Thaumarchaeota is controlled by the oxygen content dissolved in water of these lakes. Thaumarchaeota are likely to contribute only a small proportion of iGDGTs in the relatively oxygen-depleted lakes, and thus TEX_(86) is not suitable for the reconstruction of the surface temperature of these lakes. The abundance ratio of iGDGTs to bGDGTs(R_(i/b)) appears to show no relationship with water pH in all the lakes, but exhibits a significant positive correlation with the water depth of the acid Lake Qinghai in Tengchong. As expected, the methylation degree of bGDGTs(MBT′) was found to correlate with both mean annual air temperature(MAT) and water pH, and the cyclization degree of bGDGTs(CBT) correlates only with water pH in these lakes. However, the MBT′_(5ME), an index to measure the methylation degree of 5-methyl bGDGTs, exhibits no relationship with MAT, whereas MBT′_(6ME), the methylation degree of 6-methyl bGDGTs, was found to correlate significantly with MAT. This is opposite to the situation observed in the global soils, pointing to a different adaptation of b GDGT-producing bacteria to environmental variables or different microbial sources of bGDGTs in these lakes. The relative abundance of 6- vs. 5-methyl bGDGTs is controlled by pH in these lakes, similar to that observed in worldwide soils. Hence, the isomer ratio(IR) of 6-methyl bGDGTs or CBT′ can be used as a proxy for water pH, although they might be influenced by other environmental factors including temperature in the lakes with a narrow range of pH.
