CHEMICAL PAPERS
·
2014
·Vol. 68
·期 10
·1408-1414
·
IF 1.193
Cao Meng,Hu Hua-You,Zhao Hu-Cheng,Zhang Xi-Quan,Gu Hong-Mei,Yang Ling,Cai Jin,Wang Peng,Hu Bing,Ji Min
In the current study a facile synthetic route for preparing antineoplastic drug GDC-0449 is investigated. Starting with pyridine-1-oxide and 1-iodo-3-nitrobenzene, the intermediate product 2-(2-chloro-5-nitrophenyl) pyridine was prepared by cross-coupling, deoxidation and halogenation. The final compound was then synthesised by reduction of the nitro group followed by amidation. This synthetic route avoids the use of unstable organometallic or organic boride compounds; it employs relatively inexpensive and bench-stable reagents, involves readily controllable reaction conditions, and achieves a relatively high yield.
研究领域:
药物化学
·
有机合成
·
肿瘤学
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2015
·
IF 3.65
Yang Li,Yang Fu,Hongyu Guo,Lixue Zhang,Lingling Huang,Li Yang
The inherent instability of micelles remains a main challenge for antitumor drug delivery, the objective of this study is to prepare and characterize the ion-fixed mixed micelles with significantly improved stability. The mixed micelles and ion-fixed mixed micelles combining the carboxy-containing PLA (PLA-COO − ) and mPEG-PLA were formed by inserting PLA-COO − into micellar core without and with metal ions , respectively. The critical micelle concentration (CMC) of mixed micelle depended on the origin PLA length in the mPEG-PLA, whereas kinetic stability of the mixed micelles was significantly improved, irrespective of the PLA length. However, curcumin (Cur)-loaded mixed micelles did not show higher physical stability upon dilution and Cur-micelle bonding constant due to the lower loading space. On the contrary, the ion-fixed mixed micelles formed in the presence of CaCl 2 solution showed a high physical stability upon dilution due to the solidification of micellar core by forming the more hydrophobic (PLA-COO − ) 2 Ca 2+ complex. The Cur-loaded ion-fixed mixed micelles showed the comparable cellular uptake of Cur and cytotoxicity in comparison with mPEG-PLA micelles. Our study highlights a universal combining strategy of ion-fixed mixed micelles with superior stability to individual micelles for antitumor drug delivery.
研究领域:
药剂学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2013
·Vol. 10
·期 3
·599-608
·
IF 7.823
Si-Yong Qin,Jun Feng,Lei Rong,Hui-Zhen Jia,Si Chen,Xiang-Ji Liu,Guo-Feng Luo,Ren-Xi Zhuo,Xian-Zheng Zhang
Graphene oxide (GO)-based theranostic nanohybrid is designed for tumor induced imaging and potential combinational tumor therapy. The anti-tumor drug, Doxorubicin (DOX) is chemically conjugated to the poly(ethylenimine)-co-poly(ethylene glycol) (PEI-PEG) grafted GO via a MMP2-cleavable PLGLAG peptide linkage. The therapeutic efficacy of DOX is chemically locked and its intrinsic fluorescence is quenched by GO under normal physiological condition. Once stimulated by the MMP2 enzyme over-expressed in tumor tissues, the resulting peptide cleavage permits the unloading of DOX for tumor therapy and concurrent fluorescence recovery of DOX for in situ tumor cell imaging. Attractively, this PEI-bearing nanohybrid can mediate efficient DNA transfection and shows great potential for combinational drug/gene therapy. This tumor induced imaging and potential combinational therapy will open a window for tumor treatment by offering a unique theranostic approach through merging the diagnostic capability and pathology-responsive therapeutic function.
研究领域:
生物医学工程
·
纳米医学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
Polymer Chemistry
·
2015
·Vol. 6
·期 13
·2401-2406
·
IF 5.52
Rumei Cheng,Ruitao Zou,Shengju Ou,Rui Guo,Ruiying Yan,Haiyan Shi,Shanshan Yu,Xiaojian Li,Yexu Bu,Mimi Lin,Yong Liu,Liming Dai
A pH-sensitive, nanostructured antitumor drug, GO-CONH-Schiff base (GCS), was prepared from the chitosan-xanthone Schiff base (CS)-modified graphene oxide (GO) complex. The successful synthesis of GCS was confirmed using various spectroscopic techniques, including FT-IR, XPS, UV-vis and TGA. The resulting GCS showed superb antitumor activity with the pH-sensitive release of the antitumor part, CS, and decreased cytotoxicity of GCS to normal human cells. The release of CS was stable and thorough in the solution at pH 1 (the pH value for gastric juice), suggesting that the as-synthesized, pH-sensitive drug could provide new insights into the design of advanced nanostructured oral drugs.
研究领域:
纳米医学
·
药理学
·
生物材料学
✓ 已验证
DOI
高影响因子
MACROMOLECULES
·
2012
·
IF 5.167
Jianzhong Du,Lang Fan,Qiuming Liu
We have previously reported the preparation of a novel pH-sensitive and biocompatible polymer vesicle in pure water based on the spontaneous self-assembly of a diblock copolymer, PMPC-b-PDPA, where PMPC is poly[2-(methacryloyloxy)ethyl phosphorylcholine] and PDPA is poly[2-(diisopropylamino)ethyl methacrylate] ( J. Am. Chem. Soc. 2005, 127, 17982). Herein, we intend to report the strategy for controlling the pH trigger points of association/dissociation of pH-responsive polymer vesicles for anticancer drug delivery. We introduced a reactive block, poly[2-(dimethylamino)ethyl methacrylate] (PDMA) into the above diblock copolymer to form reactive PMPC-b-PDMA-b-PDPA and PMPC-b-PDPA-b-PDMA triblock copolymers, as well as PMPC-b-P(DMA-stat-DPA) block-statistical copolymer by atom transfer radical polymerization (ATRP) in methanol at room temperature. As a result of different block length of PDPA, the introduction of PDMA chain at different positions, and different initial copolymer concentrations, those block copolymer vesicles showed tunable pH trigger points and various isoelectric points (IEPs) in aqueous solution. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) studies confirmed that the block copolymers with relatively long PDPA block form polymer vesicles by simply tuning the solution pH in pure water. Above pH 6.2, the PDPA block becomes hydrophobic so it forms the vesicle membrane. In all cases, the hydrophilic PMPC chains form the vesicle coronas. The PDMA chains are designed in three different positions. In PMPC-b-PDMA-b-PDPA vesicles, the PDMA chains form the middle shell between the PDPA vesicle membrane and the PMPC vesicle corona. In PMPC-b-PDPA-b-PDMA vesicles, the PDMA can mix with PMPC to serve as mixed coronas. In PMPC-b-P(DMA-stat-DPA) vesicles, the reactive PDMA chains can be incorporated into the vesicle membrane, which provides an effective strategy regarding the immobilization of vesicles by selective quaternization of PDMA with a bifunctional cross-linker, such as 1,2-bis(2-iodoethoxy)ethane (BIEE). The degree of cross-linking can be tuned by varying the molar ratio of PDMA to BIEE, which was further investigated by 1H NMR, DLS, and TEM, suggesting tunable permeability of vesicle membrane. The triblock copolymer vesicles were able to encapsulate anticancer drugs such as DOX, exhibiting obviously retarded release profile at physiological conditions.
研究领域:
生物材料
·
药剂学
·
高分子化学
✓ 已验证
DOI
高影响因子
BIOORGANIC CHEMISTRY
·
2020
·
IF 4.831
Chao Liu,Hua Zhou,Xiao Bao Sheng,Xin Hua Liu,Fei Hu Chen
Telomerase has become one of the new popular targets for the development of anti-tumor drugs. Based on the structural characteristics of the BIBR1532 which has entered the stage of clinical research, six series total of 64 new compounds with diverse structural characteristics were designed and synthesized. The inhibitory activity against SGC-7901, MGC-803, SMMC-7721, A375 and GES cell lines and their telomerase inhibitory activity were tested. Among them, eight compounds showed good activity against cancer cells, among them compounds 56 , 57 and 59 also showed low toxicity. Some of them showed excellent telomerase inhibitory activity with IC 50 values ranging from 0.62 μM to 8.87 μM. Based on above, in depth structure-activity relationships were summarized, the compounds by replacing methyl group with cyanide and retaining amide moiety had good anti-tumor activity, moderate cytotoxicity, and better telomerase inhibitory activity. The results should be used for reference in BIBR1532-based structural optimization for further development of small molecule telomerase inhibitors.
研究领域:
药理学
·
肿瘤学
·
药物化学
✓ 已验证
DOI
PubMed
高影响因子
CHINESE JOURNAL OF CHEMICAL ENGINEERING
·
2014
·
IF 0.872
Ruiduan Li,Jianjun Zhang,Jianfeng Chen,Wei Teng,Jiexin Wang,Caixia Li
Hybrid nanoparticles based on lactide and poly(ethylene glycol) were composed of a copolymer , poly(2-amino,1,3-propanediol carbonic ester-co-lactide) [P(LA-co-CA)], and a graft copolymer , poly(2-amino,1,3-propanediol carbonic ester-co- l -lactide)-g-methoxy-poly(ethylene glycol) [P(LA-co-CA)-mPEG]. The hybrid nanoparticles were prepared using emulsion solvent diffusion method. The copolymer of poly(2-benzyloxy amide,1,3-propanediol carbonic ester-co-lactide) was prepared using ring-opening polymerization with diethylzinc (ZnEt 2 ) as a catalyst, and then took off benzyl oxygen group to obtain P(LA-co-CA). P(LA-co-CA)-mPEG by grafting methoxy-PEG-propionaldehyde (mPEG-ALD) on P(LA-co-CA). With docetaxel as a model drug, the morphology of nanoparticles was characterized by scanning electron microscopy (SEM) and the size and size distribution were determined by dynamic light scattering (DLS). The size of DTX-loaded particle was approximately 110 nm. The size scale prevents them from uptake by the reticulo-endothelial system and accumulation at the target site through the enhanced permeability and retention effect. In MTT assay, the results showed that the polymers are non-cytotoxic. The study points to the potential application of the composite nanoparticles in biomedical applications, including tissue engineering and controlled drug delivery.
研究领域:
生物材料学
·
药剂学
·
癌症治疗
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Pharmacology
·
2018
·
IF 3.831
Tsai Hsiang-I,Jiang Lijuan,Zeng Xiaowei,Chen Hongbo,Li Zihuang,Cheng Wei,Zhang Jinxie,Pan Jie,Wan Dong,Gao Li,Xie Zhenhua,Huang Laiqiang,Mei Lin,Liu Gan
The clinical applications of platinum-based antitumor agents are still largely limited by severe side effects as well as multidrug resistance (MDR). To solve these problems, we developed an 1,2-diaminocyclohexane-platinum(II) (DACHPt)-loaded nanoparticle (NP-TPGS-Pt) by self-assembly of poly(amidoamine)-polyglutamic acid-b-D-α-tocopheryl polyethylene glycol 1000 succinate (PAM-PGlu-b-TPGS) and DACHPt. NP-TPGS-Pt showed robust stability and pH-responsive DACHPt release profile in vitro similar to the PEG-containing nanoparticle (NP-PEG-Pt). Meanwhile, in contrast with NP-PEG-Pt, NP-TPGS-Pt exhibited efficient nanoparticle-based cellular uptake by the Pt-resistant A549/DDP human lung cancer cells and caused much more cytotoxicity than free Oxaliplatin and NP-PEG-Pt. Finally, this NP-TPGS-Pt was proved to perform outstanding inhibition of Pt-resistant tumor growth, much superior than free Oxaliplatin and NP-PEG-Pt. Thus, this NP-TPGS-Pt provides a novel powerful nanomedicine platform for combatting multidrug resistant cancer.
研究领域:
药学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Wenxin Zhong,Yalin Xu,Zixuan Wang,Xiyan Wang,Yaqi Li,Jinrui Liu,Can Zhao,Xianbao Shi,Zhonggui He,Bingjun Sun,Chutong Tian
Small molecule prodrugs self-assembled nano-delivery systems with tumor responsive linkages are emerging as an effective platform. However, the heterogeneity of tumor microenvironment may limit the anti-tumor effect of prodrug nanomedicines with a single response module. Here, we chose disulfide bond as the response module and branched chain alcohol as the self-assembly modification module to construct a single-responsive prodrug. We also constructed a double-responsive paclitaxel prodrug combining triglyceride and disulfide bond, taking into account of the highly expressed lipase and glutathione levels in tumor cells. The results showed that the anti-tumor effect of single-responsive branched chain alcohol modified prodrug nanoparticles was inferior to triglyceride prodrug nanoparticles with dual response modules. The triglyceride structure can not only serve as a self-assembly modification module, but also serve as a response module for intelligent drug release in tumor. Such dual roles will facilitate the efficient delivery of small molecule self-assembled prodrugs to tumor sites.
研究领域:
药学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
·
2023
·
IF 3.8
Yuandou Wang,Shuxin Wang,Wenju Hu,Shaowen Kong,Feng Su,Fusheng Liu,Suming Li
A triblock copolymer was synthesized by ring opening polymerization of ε‐caprolactone in the presence of poly(ethylene glycol) (PEG). The resulted PCL-PEG-PCL triblock copolymer, PEG and monomethoxy (MPEG) were functionalized by end group acrylation. NMR and FT-IR analyses evidenced the successful synthesis and functionalization of polymers. A series of photo-crosslinked hydrogels composed of acrylated PEG-PCL-Acr and MPEG-Acr or PEG-Acr were prepared by exposure to visible light using lithium phenyl-2,4,6-trimethylbenzoylphosphinate as initiator. The hydrogels present a porous and interconnected structure as shown by SEM. The swelling performance of hydrogels is closely related to the crosslinking density and hydrophilic content. Addition of MPEG or PEG results in increase in water absorption capacity of hydrogels. In vitro degradation of hydrogels was realized in the presence of a lipase from porcine pancreas. Various degradation rates were obtained which mainly depend on the hydrogel composition. MTT assay confirmed the good biocompatibility of hydrogels. Importantly, in situ gelation was achieved by irradiation of a precursor solution injected in the abdomen of mice. Doxorubicin (DOX) was selected as a model antitumor drug to evaluate the potential of hydrogels in cancer therapy. Drug-loaded hydrogels were prepared by in situ encapsulation. In vitro drug release studies showed a sustained release during 28 days with small burst release. DOX-loaded hydrogels exhibit antitumor activity against A529 lung cancer cells comparable to free drug, suggesting that injectable in situ hydrogel with tunable properties could be most promising for local drug delivery in cancer therapy.
研究领域:
生物材料
·
药剂学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2014
·Vol. 4
·期 103
·58982-58989
·
IF 3.708
Jing Yu,Wei Ha,Juan Chen,Yan-ping Shi
Codelivery of multiple drugs with one kind of drug carrier provides a promising strategy to suppress the drug resistance and achieve the enhanced therapeutic effect in cancer treatment. In this work, we successfully developed multifunctional supramolecular hydrogels based on in situ host–guest inclusion between polymer-drug conjugates and α-cyclodextrin to codeliver hydrophobic and hydrophilic anticancer drugs with pH-trigged release properties. Taking advantage of the strong hydrophobicity of 4β-aminopodophyllotoxin (NPOD), a derivative of podophyllotoxin (POD), the NPOD molecule was conjugated to low-molecular-weight methoxypoly (ethylene glycol) (mPEG) chain via a pH-responsive imine bond, forming an amphiphilic polymer-drug conjugates (NPOD-PEG). After adding α-cyclodextrin (α-CD) into the NPOD-PEG solutions, the stable supramolecular hydrogels were formed based on a combination of the partial inclusion complexation between one end of the mPEG blocks and α-CD and the hydrophobic aggregation of NPOD groups. The formed hydrogels could further efficiently load another hydrophilic anticancer drug doxorubicin (DOX) for combination therapy purposes. The hydrogel demonstrated unique gel–sol transition properties and pH-dependent dual drug release behavior due to the hydrolysis of imine bond at acidic environments. Furthermore, the cytotoxicity results suggested that the DOX loaded NPOD-PEG/α-CD hydrogels showed an enhanced cytotoxicity in cancer cells in comparison with single modality treatment and the resulting hydrogels are characterized by producing an additive cytotoxicity to cancer cells. In fact, the codelivery of two anticancer drugs with different physicochemical properties and anticancer mechanisms was a key to opening the door to their controlled drug delivery and enhanced anticancer effect. Therefore, DOX loaded NPOD-PEG/α-CD hydrogels as pH-trigged drug codelivery systems might have important potential for combination cancer chemotherapy.
研究领域:
药学
·
生物材料科学
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
ACS Biomaterials Science & Engineering
·
2017
·
IF 3.234
Kewei Wang,Qianqian Chen,Wei Xue,Sha Li,Zonghua Liu
In the treatment of cancers, molybdenum disulfide (MoS2) has shown great potential as a photoabsorbing agent in photothermal therapy and also as an antitumor drug delivery system in chemotherapy. However, the poor dispersibility and stability of MoS2 in aqueous solutions limit its applications in cancer therapy. To overcome the shortcomings, MoS2 was modified mainly by surface adsorption of linear polymers, such as chitosan and poly(ethylene glycol). As reported, the linear polymers could be more rapidly cleared from blood circulation than their branched counterparts. Herein, we developed hyperbranched polyglycidyl (HPG)-modified MoS2 (MoS2–HPG) by absorbing HPG on the MoS2 surface. The MoS2–HPG as a novel photoabsorbing agent was also used as a nanoscaled carrier to load antitumor drug doxorubicin hydrochloride (DOX) (MoS2–HPG–DOX) for combined chemo-photothermal therapy. The physicochemical and photothermal properties of MoS2–HPG were measured, and the results indicate that MoS2–HPG had good dispersion and stability in aqueous solutions and also high photothermal conversion efficiency. MoS2–HPG displayed good biocompatibility in hemocompatibility and cytotoxicity evaluations in vitro. Furthermore, the combined chemo-photothermal therapy using MoS2–HPG–DOX demonstrated better anticancer effect than the individual chemotherapy or photothermal therapy alone. From the results, MoS2–HPG with combined chemo-photothermal therapy could be developed as a promising therapeutic formulation for clinical cancer treatment.
研究领域:
生物医学工程
·
癌症治疗
·
纳米材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）