ROS-responsive cyclodextrin nanoplatform for combined photodynamic therapy and chemotherapy of cancer

Cyclodextrin(CD) has special spatial structure and well biological safety,so it has been widely used for constructing CD-based na noplatforms.Through functionalization,cyclodextrin can form various stimulusresponse nanoplatforms,such as pH,temperature,redox,light and magnetic fields.In this study,we designed a highly sensitive reactive oxygen species(ROS)-responsive polymer PCP which encapsulated doxorubicin(DOX) and purpurin 18(P18) to achieve the syne rgy of photodynamic and chemotherapy.The high content of reactive oxygen species(ROS) in the tumor microenvironment(TME) triggers the cleavage of the borate bond of MPEG-CD-PHB(PCP),thereby promoting the re lease of drugs.When irradiated with nea rinfrared laser,the photosensitizer P18 released by polymer micelles can produce reactive oxygen species to promote cell apoptosis.Compared with monotherapy,a series of experiments confirmed that our micelles had enhanced anti-cancer activity.This work was beneficial to the design of ROS-responsive materials and provides an effective strategy for the application of collaborative anti-tumor therapy.     

Effects of polymer molecular weight on in vitro and in vivo performance of nanoparticle drug carriers for lymphoma therapy

The clinical efficacy of chemotherapeutic drugs is hindered by their poor aqueous solubility, low bioavailability and severe side effects. In recent years, polymeric nanocarriers have been used for drug delivery to improve the efficacy of many chemotherapeutics. In this study, a series of biodegradable phenylalanine-based poly(ester amide) (Phe-PEA) with tunable molecular weights (MWs) were synthesized to systematically investigate the relationship between the polymer MW and the efficacy of the corresponding polymeric nanoparticles (NPs). The results indicated that a range of polymers with different MWs can be obtained by varying the monomer ratio or reaction time. Doxorubicin (DOX), a classic clinical lymphoma treatment strategy, was selected as a model drug. The loading capacity and stability of the higher MW polymeric NPs were superior to those of the lower MW ones. Moreover, in vitro and in vivo data revealed that high MW polymeric NPs had better anticancer efficacy against lymphoma and higher biosafety than low MW polymeric nanoparticles and DOX. Therefore, this study suggests the importance of polymer MW for drug delivery systems and provides valuable guidance for the design of enhanced polymeric drug carriers for lymphoma treatment.     

Determination of tolperisone enantiomers in plasma and their disposition in rats.

A stereoselective assay for the determination of tolperisone enantiomers in plasma by high performance liquid chromatography was developed. Calibration curves obtained for the enantiomers were linear over plasma concentrations of 0.1-3.0 micrograms/ml with a detection limit of 20 ng/ml. Following intravenous bolus administration of 10 mg/kg of racemic tolperisone to rats, stereoselective disposition of tolperisone enantiomers was observed, and plasma concentrations were significantly higher for l-tolperisone than for d-tolperisone at 5, 15 and 30 min after administration. When either enantiomer was administered alone to rats, both enantiomers were found in plasma, indicating that a mutual chiral inversion occurs in the body.     

Construction of a biotin-targeting drug delivery system and its near-infrared theranostic fluorescent probe for real-time image-guided therapy of lung cancer

The therapy of non-small lung cancer(NSCLC) is limited by wide metastasis and chemotherapy resistance, herein, we present a new cancer-targeting prodrug PBG with the integration of real-time fluorescence visualization. The potent anticancer drug Gefitinib conjugates a biotin recognition ligand yielding the prodrug PBG via a GSH-activatable disulfide bond linker. Once coupling a near-infrared azo-BODIPY fluorophore into the molecular structure of PBG, we obtain its fluorescent theranostic TBG. Th...     

Preparation of poly(butylene-co-ε-caprolactone carbonate) and their use as drug carriers for a controlled delivery system

Poly(butylene-co-ε-caprolactone carbonate) (PBCCL) was successfully synthesized via terpolymerization of carbon dioxide, 1,2-butylene oxide (BO), and ε-caprolactone (ε-CL). ε-CL was inserted into the backbone of BO-CO₂. The glass transition temperature (T_g) and the decomposition temperature (T_d) of PBCCL were much higher than those of poly(butylene carbonate) (PBC). The degradation rate of PBCCL was higher than that of PBC in a pH 7.4 phosphate-buffered solution. ε-CL offered an ester structural unit that gave the terpolymers remarkable degradability. PBC and PBCCL microcapsules containing a hydrophilic antibiotic drug pazufloxacin mesilate (PZFX) were elaborated by solvent evaporation method based on the formation of double W/O/W emulsion. Microcapsules were characterized in terms of the morphology, size, amount of encapsulated, and encapsulation efficiency. The results showed that the microcapsules had smooth and spherical surfaces, and the mean diameter of the microcapsules was in the range of 0.5–1 μm. Of all, 87.90% drug encapsulation efficiency has been achieved for microcapsules of 38.21% drug loading. In vitro drug release of these microcapsules was performed in a pH 7.4 phosphate-buffered solution. The release profiles were investigated from the measurement of PZFX presented in the release medium at various intervals. The release profiles of PZFX from PBC and PBCL microcapsules were found to be biphasic with a burst release followed by a gradual release phase. The release rate of PZFX from the microcapsules increased with increasing the content of ε-CL inserted into the copolymers. It showed that the release profiles of PZFX were highly polymer-dependent. © 2007 Wiley Periodicals, Inc. JPolym Sci Part A: Polym Chem 45: 2152–2160, 2007     

Preparation of a porphyrin-polyoxometalate hybrid and its photocatalytic degradation performance for mustard gas simulant 2-chloroethyl ethyl sulfide

By combining 5,10,15,20-tetra（4-chlorine）phenylporphyrin（TClPP） and α-Keggin polyoxometalate H₅PV₂Mo₁₀O₄₀（H₅PVMo） via a simple ion-exchange method, an organic-inorganic hybrid material[C₄₄H₂₈N₄Cl₄]_1.5[H₂PMo₁₀V₂O₄₀]·2C₂H₆O（H₂TClPP-H₂PVMo） was prepared and thoroughly characterized by a variety of techni...     

Folic acid and its derivatives for targeted photodynamic therapy of cancer

The fundamentals of folic acid and folate receptors functioning in the body, changes in the expression level of folate receptors in carcinogenesis, as well as use of folic acid and its derivatives for targeted delivery of photosensitizers to tumors have been reviewed. The ways of increasing the efficacy of photodynamic therapy by creating multifunctional nanoplatforms that ensure both passive targeting and receptor-mediated internalization of photosensitizers in tumor cells have been discussed.     

Preparation of a water-soluble fluorinated zinc phthalocyanine and its effect for photodynamic therapy

An amphiphilic fluorinated phthalocyanine, zinc tetracarboxyoctafluorophthalocyanine (ZnC4F8Pc) was synthesized and characterized. Its photodynamic efficiency for HeLa cells was compared with hydrophilic zinc octacarboxyphthalocyanine (ZnC8Pc) and hydrophobic zinc hexadecafluorophthalocyanine (ZnF16Pc). ZnC4F8Pc had a remarkable photodynamic effect among the phthalocyanines used. The effect is apparently caused by the fact that ZnC4F8Pc is mainly accumulated in the hydrophobic lipid membrane and is in the photoactive monomer form in HeLa cells.     

Preparation and characterization of a lamotrigine imprinted polymer and its application for drug assay in human serum

A molecularly imprinted polymer (MIP) against lamotrigine (LTG) was prepared, characterized, and its recognition properties were compared with a blank nonimprinted polymer (NIP). Two classes of binding sites were found in the MIP--high affinity (K(D) = 16.2 microM) and low affinity (K(D) = 161.3 microM). Selectivity of the synthesized MIP was examined using compounds with similar structures or therapeutic uses to LTG. In compounds which had structural similarity to LTG, the presence of amine groups appeared to affect binding to the MIP, however overall shape of the molecule was also important. Under the optimal conditions developed, other anticonvulsant drugs tested did not bind the MIP. A molecularly imprinted SPE (MISPE) procedure was developed which had a recovery of 84-89%, interday variation of less than 3.4% and intraday variation of less than 2.8%. The MISPE procedure was compared with a routine liquid-liquid extraction (LLE) procedure used for the HPLC determination of LTG in serum from patients. The data indicated that the MIP synthesized showed both good selectivity and high affinity for LTG and could be used for the extraction of the drug from serum samples or as the receptor layer for an LTG selective biosensor.     

环糊精在药物控制释放系统中的应用研究进展

因为环糊精的生物相容性和多功能性,通过改性以及各种剂型的设计,能够扩展其在医药领域的应用。本文介绍了环糊精及其衍生物在药物控制释放体系中的作用机理及特点,并结合本课题组的研究工作,综述了近年来环糊精在该领域中的应用研究进展。     

Highly efficient drug delivery with gold nanoparticle vectors for in vivo photodynamic therapy of cancer

A highly efficient drug vector for photodynamic therapy (PDT) drug delivery was developed by synthesizing PEGylated gold nanoparticle conjugates, which act as a water-soluble and biocompatible "cage" that allows delivery of a hydrophobic drug to its site of PDT action. The dynamics of drug release in vitro in a two-phase solution system and in vivo in cancer-bearing mice indicates that the process of drug delivery is highly efficient, and passive targeting prefers the tumor site. With the Au NP-Pc 4 conjugates, the drug delivery time required for PDT has been greatly reduced to less than 2 h, compared to 2 days for the free drug.     

Molecular drug design, synthesis and structure elucidation of a new specific target peptide based metallo drug for cancer chemotherapy as topoisomerase I inhibitor

To evaluate the biological preference of metallopeptide drugs in cancer cells, a new dinuclear copper(II) complex [Cu(2)(glygly)(2)(ppz)(H(2)O)(4)]·2H(2)O (1) (glygly = glycyl glycine anion and ppz = piperazine), was designed and synthesized as topoisomerase I inhibitor. The structural elucidation of the complex was done by elemental analysis, spectroscopic methods and single crystal X-ray diffraction. The in vitro DNA binding studies of complex 1 with CT DNA were carried out by employing different optical methods viz. UV-vis, fluorescence and circular dichroism. The molecular docking technique was also utilized to ascertain the mechanism and mode of action towards the molecular target DNA and enzymes. Complex 1 cleaves pBR322 DNA via an oxidative mechanism and strongly binds to the DNA minor groove. Furthermore, complex 1 exhibits significant inhibitory effects on the catalytic activity of topoisomerase I at a very low concentration, ~12.5 μM, in addition to its excellent SOD mimics (IC(50)~0.086 μM).     

Inhibitory effect of 2-(E-2-alkenoylamino)ethyl alkyl sulfides on gastric ulceration in rats. II. Structure and activity relationships of 2-(E-n or Z-n-Decenoylamino)ethyl alkyl sulfides

The analogues of 2-(E-n or Z-n-decenoylamino)ethyl carbamoylmethyl sulfide, including the modifications of sulfide portion, double bond in decenoyl chain and alkyl sulfide moiety, were synthesized and their inhibitory effects on stress-induced ulceration in rats were compared. Replacing the sulfura atom by methylene group or oxygen atom reduced the effect of potency. Saturation of the double bond in the decenoyl chain tended to reduce the anti-ulcerogenic activity in rats. There was no relationship between the position of double bond in decenoyl chain and the pharmacological activity. On the other hand, compounds with E-configuration showed stronger anti-ulcer activity than the corresponding Z-type of compounds. Among 9 kinds of S substituted alkyl groups for carbamoylmethyl, 2-(E-2-decenoylamino)ethyl 2-cyclohexylethyl sulfide showed the most potent anti-ulcerogenic activity in rats and also showed the lowest acute toxicity in mice.