During conventional chemotherapy for cancer, nonspecific drug distribution, which causes serious side effects in normal tissues, is a serious limitation. Thus, it is desirable to develop a tumor or intracellular micro...During conventional chemotherapy for cancer, nonspecific drug distribution, which causes serious side effects in normal tissues, is a serious limitation. Thus, it is desirable to develop a tumor or intracellular microenvironment-responsive nanosystem for targeted and on-demand drug release. In the present study, we engineered an intelligent pH-activatable nanosystem, in which a gadolinium- doxorubicin-loaded nanoscale coordination polymer （Gd-Dox NCPs） was the core and hyaluronic acid was the targeting shell. Taking advantage of CD44 receptor-mediated recognition, the nanoparticles were internalized selectively into human cervical carcinoma （HeLa） cells, and trapped within acidic compartments where the fluorescence of Dox recovered, along with the acid dismantling of the Gd NCPs, allowing real-time monitoring of drug release. In vitro experiments also showed that the Gd NCPs present enhanced T1 signals after acid-triggered degradation, suggesting their potential use as contrast agents for magnetic resonance imaging. Such nanocarriers, which feature high biodegradation, selective targeting ability, and rapid response to stimulus, demonstrated enhanced therapeutic efficacy in targeted cancer cells and ＂turned on＂T1 signals in vitro, showing great promise for diagnosis and treatment.展开更多
Dicarboxyl-functionalized salen ligand 1,2-phenylendiamine-N,N＇-bis（3-tert-butyl-5-（carboxyl）-salicylide-ene （HAL） was synthesized in good yield from 3-tert-butyl-5-formyl-4-hy- droxybenzoic acid and used to con...Dicarboxyl-functionalized salen ligand 1,2-phenylendiamine-N,N＇-bis（3-tert-butyl-5-（carboxyl）-salicylide-ene （HAL） was synthesized in good yield from 3-tert-butyl-5-formyl-4-hy- droxybenzoic acid and used to construct a 2D zinc complex, [（ZnL）Zn3/2（BDC）1/2（DMSO）2]·3DMSO （1, BDC = 1,4-benzenedicarboxylate）, under mild reaction conditions. 1 was characterized by IR, microanalysis, TGA and single-crystal X-ray crystallography. It crystallizes in triclinic space group P^-1 with a = 11.3860（4）, b = 13.2636（5）, c = 17.5503（7） A, α = 92.2240（10）, β = 94.5070（10）, γ = 96.0580（10）°, V= 2624.52（17） A^3, Z = 2, Mr = 1143.62, Dc = 1.448 g/cm^3, F（000） = 1186, g = 1.395 mm^-1, GOOF = 0.993, the final R = 0.0380 and wR = 0.1280 for 21752 observed reflections with I 〉 20（I）. The 2D coordination polymer 1 is further assembled into a 3D supramolecular network structure via π…π interactions between the aromatic rings of the ligands in adjacent layers. Thermal gravimetric analysis demonstrates that 1 is a thermally robust structure with network decomposition temperatures of 420 ℃ and it also exhibits strong photoluminescence in the visible region.展开更多
文摘During conventional chemotherapy for cancer, nonspecific drug distribution, which causes serious side effects in normal tissues, is a serious limitation. Thus, it is desirable to develop a tumor or intracellular microenvironment-responsive nanosystem for targeted and on-demand drug release. In the present study, we engineered an intelligent pH-activatable nanosystem, in which a gadolinium- doxorubicin-loaded nanoscale coordination polymer （Gd-Dox NCPs） was the core and hyaluronic acid was the targeting shell. Taking advantage of CD44 receptor-mediated recognition, the nanoparticles were internalized selectively into human cervical carcinoma （HeLa） cells, and trapped within acidic compartments where the fluorescence of Dox recovered, along with the acid dismantling of the Gd NCPs, allowing real-time monitoring of drug release. In vitro experiments also showed that the Gd NCPs present enhanced T1 signals after acid-triggered degradation, suggesting their potential use as contrast agents for magnetic resonance imaging. Such nanocarriers, which feature high biodegradation, selective targeting ability, and rapid response to stimulus, demonstrated enhanced therapeutic efficacy in targeted cancer cells and ＂turned on＂T1 signals in vitro, showing great promise for diagnosis and treatment.
基金supported by NSFC-21025103 and 20971085"973" Programs (2007CB209701 and 2009CB930403)+1 种基金Shanghai Science and Technology Committee (10DJ1400100)the key project of State Education Ministry
文摘Dicarboxyl-functionalized salen ligand 1,2-phenylendiamine-N,N＇-bis（3-tert-butyl-5-（carboxyl）-salicylide-ene （HAL） was synthesized in good yield from 3-tert-butyl-5-formyl-4-hy- droxybenzoic acid and used to construct a 2D zinc complex, [（ZnL）Zn3/2（BDC）1/2（DMSO）2]·3DMSO （1, BDC = 1,4-benzenedicarboxylate）, under mild reaction conditions. 1 was characterized by IR, microanalysis, TGA and single-crystal X-ray crystallography. It crystallizes in triclinic space group P^-1 with a = 11.3860（4）, b = 13.2636（5）, c = 17.5503（7） A, α = 92.2240（10）, β = 94.5070（10）, γ = 96.0580（10）°, V= 2624.52（17） A^3, Z = 2, Mr = 1143.62, Dc = 1.448 g/cm^3, F（000） = 1186, g = 1.395 mm^-1, GOOF = 0.993, the final R = 0.0380 and wR = 0.1280 for 21752 observed reflections with I 〉 20（I）. The 2D coordination polymer 1 is further assembled into a 3D supramolecular network structure via π…π interactions between the aromatic rings of the ligands in adjacent layers. Thermal gravimetric analysis demonstrates that 1 is a thermally robust structure with network decomposition temperatures of 420 ℃ and it also exhibits strong photoluminescence in the visible region.
