POLYMER
·
2019
·
IF 3.771
Lipeng Wang,Qing Zhu,Yongping Bai
A series of water soluble polyamides were synthesized via melt-polycondensation using glutaric acid and poly(propylene glycol) bis(2-aminopropyl ether) as monomers . The chemical structures of the polyamides were ascertained by FT-IR and 1 H NMR. The thermal properties of the polyamides under consideration were measured by TGA and DSC . It was found that one kind of the polyamides can self-assemble into nano-size vesicles with densely packed multilayer wall in aqueous solution, while another polyamide can self-assemble into large complex micelles . Interestingly, these large complex micelles display a unique acid sensitive characteristic according to the TEM and PST measurements.
研究领域:
高分子化学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2023
·
IF 5
Xinran Wang,Jieyi Pan,Haohui Shi,Na Liang,Shaoping Sun
This study was aimed at fabricating tumor targeting and acid-responsive micelles as carriers for paclitaxel (PTX). An amphipathic polymer TOS-Ace-PEG-Bio was designed and synthesized by conjugating α-tocopherol succinate (TOS) with biotinylated polyethylene glycol (PEG-Bio) via acetal bond. The polymer could self-assemble into nanosized micelles and encapsulate PTX. The PTX-loaded micelles possessed appropriate particle size with the mean value of 129.3 ± 0.9 nm . Strong pH dependent PTX release behavior was verified by in vitro drug release study. At cellular level, the PTX-loaded micelles could be selectively internalized by MCF-7 cells. The in vivo study also confirmed their excellent antitumor activity and reduced side effects. Based on these features, the TOS-Ace-PEG-Bio micelles were considered to be promising carriers for delivery of PTX.
研究领域:
药剂学
·
肿瘤学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Hongying Xiao,Jinrui Liu,Minglong Huang,Wenfeng Zang,Bowen Zhang,Shufang Zheng,Xin Li,Zhonggui He,Xin Wang,Huaiwei Ding,Lingxiao Li,Bingjun Sun
The rational design of doxorubicin (DOX)-based delivery platforms with efficient and selective features remains a major challenge. The launch of Amphotec®, formed by assembling the positive electrical amphotericin B with negatively electrical sodium cholesterol sulfate (SCS), provides effective reference. Herein, we prepared an acid-sensitive prodrug (DOX-C14) by linking DOX with myristic acid (C14) via the acylhydrazone bond. Then, the positively electrical DOX-C14 was assembled with various negatively electrical cholesterol analogs in different molar ratios to optimize the stable DOX-C14 nanocomplex. Under the combined action of electrostatic and hydrophobic forces, nanocomplexes formed by DOX-C14 with SCS at ratios of 1:2 (DOX-C14-SCS (1:2)) and 1:3 (DOX-C14-SCS (1:3)) exhibited excellent performance. Subsequently, DOX-C14-SCS (1:2) and DOX-C14-SCS (1:3) were modified with DSPE-PEG 2k or CHOL-PEG 2k to further improve their stability and pharmacokinetic behavior. As a result, the obtained PEGylated nanocomplexes could efficiently accumulate in the tumor and then released DOX to exert antitumor effects under the stimulation of acidic environment. Meanwhile, there is no significant toxicity to normal tissues even at very high doses (10 mg/kg equivalent to DOX), demonstrating superior tumor selectivity. Our findings provide novel insights into the rational design of positive electrical drug for efficient and selective cancer therapy.
CAS / MDL:
研究领域:
药学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2021
·
IF 5.268
Jingyi Liu,Zhoutong Dai,Yu Zhou,Wangwang Tao,Hongxiang Chen,Zuyi Zhao,Xinghua Liao
In order to obtain drug delivery carriers with good stability in blood and high cellular uptake efficiency, carboxyl groups and tertiary amine groups were respectively introduced into polyurethane to synthesize two kinds of amphiphilic polyurethanes with opposite charges (PUC and PUN). Their structures were characterized by Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance ( 1 H NMR) spectroscopy and gel permeation chromatography (GPC). PUC-PUN co-assembled nanomicelles were prepared by electrostatic interaction between PUC and PUN micelles , which showed acid-sensitive property. When the pH of the solution was decreased from 7.4 to 6.5, PUC-PUN-1 micelles showed negative-to-positive charge-reversal property among these micelles. The results of stability and cell experiments demonstrated that PUC-PUN-1 micelles not only had excellent stability in simulated normal physiological environment but also could obviously enhance the cellular uptake efficiency. PUC-PUN-1 micelles had low cytotoxicity against SGC-7901 and MGC-803 cells, whereas PUC-PUN-1/DOX micelles had higher cytotoxicity compared to pure DOX and PUN-1/DOX micelles. Moreover, the results of in vivo antitumor activity experiments showed that PUC-PUN-1/DOX micelles had better tumor inhibition ability and safety than pure DOX. In addition, the results of in vitro drug release experiments indicated that PUC-PUN-1/DOX micelles had almost no burst release or leakage of drugs in pH 7.4 environment. However, the drug release was accelerated in pH 5.0, which followed Fickian diffusion mechanism.
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
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2011
·
IF 4.304
Lihong Zhang,Saijie Zhu,Lili Qian,Yuanying Pei,Yongming Qiu,Yanyan Jiang
This work was based on our recent studies that a promising conjugate, RGD-modified PEGylated polyamidoamine (PAMAM) dendrimer with doxorubicin (DOX) conjugated by acid-sensitive cis -aconityl linkage (RGD-PPCD), could increase tumor targeting by binding with the integrin receptors overexpressed on tumor cells and control release of free DOX in weakly acidic lysosomes. To explore the application of RGD-PPCD to glioma therapy, the effects of the conjugate were further evaluated in glioma model. For comparative studies, DOX was also conjugated to PEG–PAMAM by acid-insensitive succinic linkage to produce the PPSD conjugates, which was further modified by RGD to form RGD-PPSD. In vitro cytotoxicity of the acid-sensitive conjugates against C6 cells was higher than that of the acid-insensitive ones, and further the modification of RGD enhanced the cytotoxicity of the DOX-polymer conjugates as a result of the increased cellular uptake of the RGD-modified conjugates by C6 cells. In vivo pharmacokinetics, biodistribution and antitumor activity were investigated in an orthotopic murine model of C6 glioma by i.v. administration of DOX-polymer conjugates. In comparison with DOX solution, all the conjugates showed significantly prolonged half-life and increased AUC and exhibited higher accumulation in brain tumor than normal brain tissue. Although RGD-PPCD was more than 2-fold lower tumor accumulation than RGD-PPSD, it exhibited the longest survival times among all treatment groups, and therefore, RGD-PPCD conjugate provide a desirable candidate for targeted therapy of glioma.
研究领域:
药理学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2018
·
IF 5.738
Junhua Li,Xuequan Zhang,Mingying Zhao,Lihuang Wu,Kui Luo,Yuji Pu,Bin He
Nanoparticle- and microsphere-based drug delivery systems (DDSs) have attracted wide attention in cancer therapy; those DDSs that are responsive to tumor environment can selectively identify tumor and normal tissues and therefore have shown enhanced anticancer efficacy and alleviated systemic toxicity. Here, tumor-pH-sensitive polymeric microspheres, which are prepared by multiblock poly(l-lactide) with pH-sensitive acetal bonds in the backbone, are employed to efficiently load water-soluble anticancer drug doxorubicin hydrochloride (DOX·HCl, drug loading content: ∼10%). The pH-sensitive DOX-loaded hollow microspheres were in the size range 2–10 μm and exhibited acid-accelerated degradation of polymer matrix and drug release, and thereby efficient in vitro cancer cell inhibition. The microspheres were further intratumorally injected into breast-tumor-bearing mice, and the in vivo anticancer experiment showed that pH-sensitive DOX-loaded microsphere showed better antitumor efficiency and prolonged life-span than its counterpart that does not have pH-responsive property. Moreover, negligible organ toxicity, especially cardiotoxicity that generally exists in DOX-involved chemotherapy where DOX is administrated by intravenous injection, was observed for DOX-loaded microspheres. Hence, tumor-pH-sensitive polymeric microspheres have appeared to be a simple and efficient platform for delivering hydrophilic anticancer drug with excellent anticancer efficacy and low systemic toxicity.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE
·
2017
·Vol. 52
·期 16
·9430-9440
·
IF 2.599
Duan Xiao,Wu Yalan,Ma Mengsi,Du Junjie,Zhang Shan,Chen Heng,Kong Jie
A new type of acid-sensitive 100% hyperbranched polyacetals (HBPA) was synthesized, which could be completely degraded into small molecules under acidic environment and avoid the accumulative toxicity in vivo. The AB 2 monomer was synthesized by 4-carboxybenzaldehyde and 2-bromoethanol. The bulk polycondensation was carried out in vacuum environment to remove water byproduct. The massive terminal aldehyde groups of HBPA were conjugated with mPEG-NH 2 and doxorubicins to form amphiphilic acid-sensitive polymer–drug conjugates (DOX-HBPA-PEG). The stability of the micelles of DOX-HBPA-PEG was evaluated by DLS at different pH value in phosphate buffer saline (PBS). The DOX release in vitro showed that the cumulative release rate was 14.51% in pH 7.4 PBS after 24 h and the cumulative release rate was 48.56% in pH 6.0 PBS after 24 h. The results of cell viability of DOX-HBPA-PEG and HBPA-PEG showed that the polymer–DOX conjugates were effective drug delivery systems. The uptake process of DOX-HBPA-PEG by A549 cells showed that the micelle was totally swallowed in 1 h later. The controllable drug release nature, stability, biocompatibility and completely degradable structures (acid-sensitive) make them to be promising drug delivery systems.
研究领域:
生物材料学
·
药学
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
Small
·
2024
·
IF 13
Zhoujiang Chen,Lianlin Long,Ji Wang,Mingli Jiang,Wei Li,Wenguo Cui,Liang Zou
The extracellular matrix (ECM) engages in regulatory interactions with cell surface receptors through its constituent proteins and polysaccharides. Therefore, nano-sized extracellular matrix conjugated with doxorubicin (DOX) is utilized to produce extracellular matrix-drug conjugates (ECM-DOX) tailored for targeted delivery to cancer cells. The ECM-DOX nanoparticles exhibit rod-like morphology, boasting a commendable drug loading capacity of 4.58%, coupled with acid-sensitive drug release characteristics. Notably, ECM-DOX nanoparticles enhance the uptake by tumor cells and possess the ability to penetrate endothelial cells and infiltrate tumor multicellular spheroids. Mechanistic insights reveal that the internalization of ECM-DOX nanoparticle is facilitated through clathrin-mediated endocytosis and macropinocytosis, intricately involving hyaluronic acid receptors and integrins. Pharmacokinetic assessments unveil a prolonged blood half-life of ECM-DOX nanoparticles at 3.65 h, a substantial improvement over the 1.09 h observed for free DOX. A sustained accumulation effect of ECM-DOX nanoparticles at tumor sites, with drug levels in tumor tissues surpassing those of free DOX by several-fold. The profound therapeutic impact of ECM-DOX nanoparticles is evident in their notable inhibition of tumor growth, extension of median survival time in animals, and significant reduction in DOX-induced cardiotoxicity. The ECM platform emerges as a promising carrier for avant-garde nanomedicines in the realm of cancer treatment.
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
·
2013
·
IF 3.172
Nan-Nan Li,Jiantao Lin,Di Gao,Li-Ming Zhang
A novel macromolecular prodrug strategy was developed for the combinatorial delivery of two poorly water-soluble drugs, dexamethasone and doxorubicin. In this work, dexamethasone was firstly conjugated onto a water-soluble modified polysaccharide by an acid-labile hydrazone linkage. The resultant macromolecular prodrug had an amphiphilic character and could self-assemble into spherical polymeric micelles in aqueous system. With these micelles, doxorubicin was then encapsulated into their hydrophobic cores. For the conjugated dexamethasone and encapsulated doxorubicin, they could exhibit independent and acid-sensitive release characteristics. For the doxorubicin-loaded prodrug micelles, they were easily be internalized by living cells and showed obvious antitumor activity.
研究领域:
药学
·
生物医学工程
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2020
·
IF 3.99
Guoping Li,Mingliang Pei,Peng Liu
Novel tumor nanotheranostics were designed by conjugating doxorubicin (DOX) onto the hydrazine-functionalized crosslinked carbon quantum dots (CQDs)/polyethylene glycol bisacrylate (PEGBA) (C-CQD PEGBA -Hy) nanosponges via an acid-labile imine bond for the tumor intracellular real-time imaging and pH-triggered DOX release. The proposed prodrug nanotheranostics with a DOX content of 14.57 % and a mean hydrodynamic diameter around 116 nm showed excellent pH-triggered drug release performance, with a cumulative release of 52.71 % in the simulated tumor intracellular microenvironment in 4 days, while a premature drug leakage of 7.09 % in the simulated normal physiological medium. Besides, the fluorescence could be recovered during the drug release, indicating the potential application for tumor intracellular real-time imaging.
研究领域:
药学
·
生物医学工程
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
RSC Advances
·
2022
·Vol. 12
·期 43
·28021-28033
·
IF 4.036
Xiaojie Chang,Guizhi Zhao,Chang Liu,Xueshi Wang,Ahmed Mohammed Ali Abdulkhaleq,Jie Zhang,Xibin Zhou
Red emissive carbon dots (R-CDs) have received great attention in biological fields due to their deep tissue penetrability, great bioimaging capability, low interference from auto-fluorescence, and potential for optoelectronic applications. Herein, excitation-independent, highly acid-sensitive R-CDs were successfully obtained via one-step microwave treatment of o-phenylenediamine (o-PD) and phosphoric acid and carefully purified by column chromatography. The relationship between the fluorescence emission and surface groups of the R-CDs was studied in detail using XPS, NMR, and fluorescence spectroscopy, and the different mechanisms of action of the R-CDs and acid in H2O and ethanol were determined. The excellent anti-interference ability and biocompatibility of the R-CDs were confirmed, and the probes were successfully used for imaging A549 and Escherichia coli (E. coli) cells in extreme acidity. Finally, based on their relatively high quantum yield and long wavelength emission, the application potential of the R-CDs in the fabrication of red light-emitting diodes (LEDs) was investigated.
研究领域:
材料科学
·
生物医学工程
·
光学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCONJUGATE CHEMISTRY
·
2018
·
IF 4.485
Chao-Ran Xu,Liang Qiu,Cai-Yuan Pan,Chun-Yan Hong,Zong-Yao Hao
In this study, an efficient method is proposed for the synthesis of polymer prodrug with acid-liable linkage via thiol–acrylate Michael addition reaction of the camptothecin with tethering acrylate group and polymer scaffold containing multiple thiol groups. The polymer scaffold P(HEO2MA)-b-P(HEMA-DHLA) is prepared by reversible addition–fragmentation chain transfer (RAFT) polymerization of the methacrylate of lipoic acid (HEMA-LA) using poly(2-(2-hydroethoxy) ethyl methacrylate) (PHEO2MA) as macro-RAFT agent followed by reduction of the disulfides in lipoic acid (LA) groups to give polymer scaffold with dihydrolipoic acid (DHLA) pendent groups. Acrylate-tethering camptothecin (ACPT) is connected to P(HEO2MA)-b-P(HEMA-DHLA) via Michael addition reaction between thiol and acrylate with a high coupling efficiency (95%). Amphiphilic polymer prodrug P(HEO2MA)-b-P(HEMA-DHLA-CPT) spontaneously self-assembles into nanoparticles in an aqueous solution and exhibits a CPT loading content as high as 40.1%. The prodrug nanoparticles with the acid-liable β-thiopropionate linkages can release CPT under acidic conditions, and the prodrug nanoparticles show similar cytotoxicity to HeLa cells as free CPT. Overall, the prodrug nanoparticles with high drug loading contents and acid-liable linkages are promising for pH-responsive anticancer therapy.
研究领域:
药学
·
生物材料
·
肿瘤学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）