JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2018
·
IF 1.911
Nahla Rahoui,Bo Jiang,Nadia Taloub,Mohammad Hegazy,Yu Dong Huang
The accuracy of spatiotemporal control cargo delivery and release are primordial to enhance the therapeutic efficiency and decrease the undesirable effects, in this context a novel prodrug were developed based on biocompatible polyvinyl alcohol (PVA) substrate. PVA was conjugated to doxorubicin (PVA-DOX) via an acid-labile hydrazone linkage. PVA was first functionalized with acidic groups, then reacted with hydrazine hydrate to form an amide bond. The amine group of PVA hydrazide was linked to carbonyl group (C = O) of DOX to form a pH sensitive hydrazone bond. The molecular structure of the PVA-DOX was confirmed by FTIR, XPS, and 1H-NMR analysis methods. The degree of grafting were evaluated by TGA and confirmed by XPS, which reveals the successful bond attachment of DOX to PVA. Our findings confirm pH dependent DOX release from PVA-DOX prodrug with faster release rate in acidic environment (pH 5.0, pH 6.0) and slower release rate in neutral pH environment (pH 7.4). Compared to the primary DOX, our synthesized PVA-DOX conjugates could exhibit a promising therapeutic effect, high biocompatibility and zero premature release. The results prove the successful synthesis of PVA-DOX conjugates with high efficiency.
研究领域:
药剂学
·
生物材料学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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
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
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
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肿瘤学
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2017
·Vol. 7
·期 66
·41919-41928
·
IF 3.108
Chaoping Fu,Rui-Meng Yang,Li Wang,Nan-nan Li,Meng Qi,Xiang-dong Xu,Xin-hua Wei,Xin-Qing Jiang,Li-Ming Zhang
For combinatorial monitoring and chemotherapy of hepatocellular carcinoma, the macromolecular prodrug based on hyaluronic acid and doxorubicin hydrochloride was prepared by an acid-labile hydrazone linkage, and then conjugated with amine-modified iron oxide nanoparticles by a carbodiimide mediated coupling reaction. The resultant hybrid nanoparticles have the characteristics of good water dispersibility, superparamagnetic property and high magnetic relaxivity for magnetic resonance imaging. In particular, they demonstrated significant cellular uptake and specific accumulation in human hepatocellular liver carcinoma HepG2 cells due to specific biological recognition of hyaluronic acid. In addition, in vitro cumulative release of doxorubicin hydrochloride from the resultant hybrid nanoparticles was significantly accelerated at a mildly acidic pH of 5.0–6.0 when compared to its release at the physiological pH of 7.4, suggesting the pH-responsive feature of this conjugated prodrug for effective chemotherapy of hepatocellular carcinoma. In vivo antitumor efficacy of the mice further confirmed the effect.
研究领域:
生物医学工程
·
肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 16
·3837
·
IF 4.2
Yanru Hu,Peng Liu
The diselenide bond has attracted intense interest for drug delivery systems (DDSs) for tumor chemotherapy, owing to it possessing higher redox sensitivity than the disulfide one. Various redox-responsive diselenide-containing carriers have been developed for chemotherapeutics delivery. However, the premature drug leakage from these DDSs was significant enough to cause toxic side effects on normal cells. Here, a pH/redox co-triggered degradable polyprodrug was designed as a drug self-delivery system (DSDS) by incorporating drug molecules as structural units in the polymer main chains, using a facile one-pot two-step approach. The proposed PDOX could only degrade and release drugs by breaking both the neighboring acid-labile acylhydrazone and the redox-cleavable diselenide conjugations in the drug’s structural units, triggered by the higher acidity and glutathione (GSH) or reactive oxygen species (ROS) levels in the tumor cells. Therefore, a slow solubility-controlled drug release was achieved for tumor-specific chemotherapy, indicating promising potential as a safe and efficient long-acting DSDS for future tumor treatment.
研究领域:
生物医学工程
·
药剂学
·
肿瘤学
✓ 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
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
POLYMER INTERNATIONAL
·
2020
·Vol. 69
·期 7
·619-626
·
IF 2.574
Liping Yin,Yanli Bao,Lin Liu,Jinze Wang,Li Chen
In clinical treatment, multidrug resistance (MDR) is one of the major obstacles resulting in the failure of chemotherapy. It is still a challenge to overcome MDR. Herein, we fabricated intelligent dextran-based dual-drug delivery systems histidine modified dextran conjugated doxorubicin/zinc porphyrin/paclitaxel (DHTD/Zn-TPP/PTX) via supramolecular metallo-coordination for synergistic chemo-photodynamic therapy to overcome cancer drug resistance. In this designed DHTD/Zn-TPP/PTX, one anticancer drug (doxorubicin, DOX) was conjugated on the dextran backbone through a reactive oxygen species sensitive linker and the other drug PTX was encapsulated into the acid responsive supramolecular micelles formed by the photosensitizer Zn-TPP and histidine grafted on dextran. DHTD/Zn-TPP/PTX with excellent stability could be effectively internalized by tumour cells. In the acidic tumour environment, the loaded PTX and Zn-TPP as photosensitizer could be released; moreover, when irradiated with light the conjugated DOX could be specifically released because the linker broke. As the obtained data indicate, DHTD/Zn-TPP/PTX exhibited not only an enhanced anticancer therapeutic effect but also significant growth inhibition for drug-resistant MCF-7/ADR cells to reverse MDR, having great potential for synergistic treatments of cancer to overcome MDR. © 2020 Society of Chemical Industry
研究领域:
肿瘤学
·
药物递送
·
生物材料
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）