RESUMEN
Coencapsulation of chemotherapeutic agents and photosensitizers into nanocarriers can help to achieve a combination of chemotherapy and photodynamic therapy for superior antitumor effects. However, precise on-demand drug release remains a major challenge. In addition, the loaded photosensitizers usually tend to aggregate, which can significantly weaken their fluorescent signals and photodynamic activities. To address these issues, herein, a smart nanocarrier termed as singlet oxygen-responsive nanoparticle (SOR-NP) was constructed by introducing singlet oxygen (1O2)-sensitive aminoacrylate linkers into amphiphilic mPEG-b-PCL copolymers. Boron dipyrromethene (BDP) and paclitaxel (PTX) as model therapeutic agents were coloaded into an 1O2-responsive nanocarrier for realizing light-controlled drug release and combination cancer treatment. This polymeric nanocarrier could substantially relieve the aggregation of encapsulated BDP due to the presence of a long hydrophobic chain. Therefore, the formed SOR-NPBDP/PTX nanodrug could generate bright fluorescent signals and high levels of 1O2, which could mediate cell death via PDT and rupture aminoacrylate linker simultaneously, leading to collapse of SOR-NPBDP/PTX and subsequent PTX release. The light-triggered drug release and combined anticancer effects of SOR-NPBDP/PTX were validated in HepG2 and MCF-7 cancer cells and H22 tumor-bearing mice. This study provides a promising strategy for tumor-specific drug release and selective photodynamic-chemo combination treatment.
Asunto(s)
Antineoplásicos/uso terapéutico , Portadores de Fármacos/química , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Fármacos Fotosensibilizantes/uso terapéutico , Acrilatos/síntesis química , Acrilatos/química , Animales , Antineoplásicos/química , Compuestos de Boro/química , Compuestos de Boro/uso terapéutico , Línea Celular Tumoral , Portadores de Fármacos/síntesis química , Liberación de Fármacos , Femenino , Humanos , Ratones , Paclitaxel/química , Paclitaxel/uso terapéutico , Fotoquimioterapia , Fármacos Fotosensibilizantes/química , Poliésteres/síntesis química , Poliésteres/química , Polietilenglicoles/síntesis química , Polietilenglicoles/química , Pirroles/química , Pirroles/uso terapéutico , Oxígeno Singlete/metabolismoRESUMEN
A new series of 1,4-dipegylated zinc(II) phthalocyanines have been synthesised and spectroscopically characterised. The derivatives ZnPc[O(CH(2)CH(2)O)(n)Me](2) (n = 2, 4, ca. 12) have been prepared by mixed cyclisation of the corresponding disubstituted phthalonitriles with an excess of unsubstituted phthalonitrile in the presence of Zn(OAc)(2) x 2 H(2)O and 1,8-diazabicyclo[5.4.0]undec-7-ene. The other two analogues ZnPc[O(CH(2)CH(2)O)(n)Me](2) (n = 6, 8) have been prepared by chain elongation reaction of ZnPc[O(CH(2)CH(2)O)(4)H](2). These macrocycles are highly soluble and remain non-aggregated in DMF as shown by the sharp Q-band absorption. Compared with the unsubstituted zinc(II) phthalocyanine, these di-alpha-substituted analogues have a red-shifted Q band (at 689 vs. 670 nm) and exhibit a relatively weaker fluorescence emission and a higher efficiency at generating singlet oxygen. Upon illumination, these compounds are highly cytotoxic toward HT29 human colorectal carcinoma and HepG2 human hepatocarcinoma cells. The compounds with medium-length substituents are particularly potent, having IC(50) values as low as 0.02 microM. The high photodynamic activity of these compounds can be attributed to their high cellular uptake and low aggregation tendency in the biological media, which promote the generation of reactive oxygen species inside the cells. The effects of the chain length on the aggregation behaviour, photophysical properties, cellular uptake and in vitro photodynamic activities of this series of compounds have also been examined.
Asunto(s)
Indoles/química , Compuestos Organometálicos/química , Compuestos Organometálicos/farmacología , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Zinc/química , Absorción , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Diseño de Fármacos , Electrones , Humanos , Isoindoles , Compuestos Organometálicos/síntesis química , Fármacos Fotosensibilizantes/síntesis química , Polietilenglicoles/química , Análisis EspectralRESUMEN
This study investigated the role of extracellular polymeric substances (EPSs) in enhanced performance of phosphorus (P) release from waste activated sludge (WAS) by adding rhamnolipid (RL). Results showed that compared to WAS without pretreatment, the released PO4(3-)-P increased with RL addition from 0 to 0.2 g/gTSS (total suspended solid), and increased by 208% under the optimal condition (0.1 g RL/g TSS and 72-h fermentation time). The cumulative PO4(3-)-P was better fitted with pseudo-first-order kinetic model. Moreover, the contents of metal ions increased in liquid but decreased in EPSs linearly with RL addition increasing, and WAS solubilizations were positively correlated with the released metal ions. The enhanced total dissolved P mainly came from cells and others (69.39%, 2.27-fold higher than that from EPSs), and PO4(3-)-P was the main species in both liquid and loosely bound EPSs, but organic P should be non-negligible in tightly bound EPSs.