RESUMO
pH/temperature dual-responsive hybrid micelles were prepared for constructing a double-locked drug delivery system. The temperature-sensitive polyethylene glycol-poly(tetrahydropyranylmethacrylate)-polyethylene glycol (PEG-PTHPMA-PEG) triblock copolymers were synthesized by reversible addition-fragmentation chain transfer polymerization and amide coupling reaction. pH-sensitive poly(2-(diisopropylamino ethylmethacrylate)-polyethylene glycol (PDPA-PEG) diblock polymers were introduced, which could self-assemble with PEG-PTHPMA-PEG in aqueous solutions to form hybrid micelles. The anticancer drug doxorubicin, which was encapsulated in the core of the hybrid micelles, could be released only under simultaneous stimulations of pH and temperature. It was proved that the micelles could maintain their structural stability under a unilateral stimulus, while the structure collapsed and recombined under a double stimulus, which triggered a large amount of drug release. Furthermore, the excellent biocompatibility and dual sensitivity of the vector were also proved by cytotoxicity experiments. The dual-responsive hybrid micelles designed here showed the advantages of a double insurance lock of drug leakage and precise controllability of drug release, which could act as accurate drug delivery systems.
Assuntos
Doxorrubicina , Micelas , Doxorrubicina/toxicidade , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Polietilenoglicóis , TemperaturaRESUMO
Using boron-doped diamond (BDD) anodes to degrade bisphenol A (BPA) had been an active area of research interest within the past 20 years. A major concern about the process lie in the formation of toxic chlorinated aromatic by-products when chloride electrolytes were present in the reaction system. In this contribution, we highlighted the formation of complex poly-chlorinated oligomer by-products in electrochemical oxidation processes, which had often been overlooked in previous studies. Moreover, the distribution and complexity of the chlorinated oligomers were found to be strongly linked to the adopted initial chloride concentration. Formation of simple chlorinated by-products was ascribed to the electrophilic substitution reactions mediated by active chlorine species, while the oligomer by-products (including chlorinated dimers, trimers and tetramers) were generated through the coupling reactions between various chlorinated phenoxy radicals. The possible mechanisms describing the formation of these by-products were also proposed. The obtained results shed light on the possible risk of BDD technology in the treatment of phenolic wastewater containing chloride electrolytes.
Assuntos
Cloretos , Poluentes Químicos da Água , Compostos Benzidrílicos , Boro , Diamante , Técnicas Eletroquímicas , Eletrodos , Oxirredução , FenóisRESUMO
Noninvasive and specific visualization of lysosomes by fluorescence technology is critical for studying lysosomal trafficking in health and disease and for evaluating new cancer therapeutics that target tumor cell lysosomes. To date, there are two basic types of lysosomal probes whose lysosomal localization correlates with lysosomal acidity and endocytosis pathway, respectively. However, the former may suffer from pH-sensitive lysosomal localization and alkalization-induced lysosomal enzyme inactivation, and the latter need long incubation time to penetrate cell membrane due to the energy-dependency of endocytosis process. In this work, a new class of two-photon fluorescent dyes, termed amino-Si-rhodamines (ASiRs), were developed, which possess the intrinsic lysosome-targeted ability that is independent of lysosomal acidity and endocytosis pathway. As a result, ASiRs show not only the stable lysosomal localization against lysosomal pH changes and negligible interference to lysosomal function, but also excellent cell-membrane-permeability due to the energy-independent passive diffusion pathway. These merits, coupled with their excellent two-photon photophysical properties, long-term retention ability in lysosomes, and negligible cytotoxicity, make ASiRs very suitable for real-time and long-term tracking of lysosomes in living cells or tissues without interference to normal cellular processes. Moreover, the easy functionalization via amino linker further allows the construction of various fluorescent probes for biological targets of interest based on ASiR skeleton, as indicated by the cancer-targeted fluorescent probe ASiR6 as well as a fluorescent peroxynitrite probe ASiR-P.
Assuntos
Corantes Fluorescentes , Lisossomos , Rodaminas , Animais , Transporte Biológico , Células COS , Chlorocebus aethiops , Endocitose , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Células Hep G2 , Humanos , Lisossomos/efeitos dos fármacos , Camundongos , Camundongos Nus , Microscopia de Fluorescência por Excitação Multifotônica , Células RAW 264.7 , Rodaminas/síntese química , Rodaminas/químicaRESUMO
Lysosomes have recently been regarded as the attractive pharmacological targets for selectively killing of cancer cells via lysosomal cell death (LCD) pathway that is closely associated with reactive oxygen species (ROS). However, the details on the ROS-induced LCD of cancer cells are still poorly understood, partially due to the absence of a lysosome-targetable, robust, and biocompatible imaging tool for ROS. In this work, we brought forward a Si-rhodamine-based fluorescent probe, named PSiR, which could selectively and sensitively image the pathologically more relavent highly reactive oxygen species (hROS: HClO, HO, and ONOO-) in lysosomes of cancer cells. Compared with many of the existing hROS fluorescent probes, its superiorities are mainly embodied in the high stability against autoxidation and photoxidation, near-infrared exitation and emission, fast fluorescence off-on response, and specific lysosomal localization. Its practicality has been demonstrated by the real-time imaging of hROS generation in lysosomes of human non-small-cell lung cancer cells stimulated by anticancer drug ß-lapachone. Moreover, the probe was sensitive enough for basal hROS in cancer cells, allowing its further imaging applications to discriminate not only cancer cells from normal cells, but also tumors from healthy tissues. Overall, our results strongly indicated that PSiR is a very promising imaging tool for the studies of ROS-related LCD of cancer cells, screening of new anticancer drugs, and early diagnosis of cancers.