Current Drug Delivery
·
2022
·Vol. 19
·期 4
·491-507
·
IF 3.758
Zhao Xinghua,Ding Shi,Li Shengnan,Wang Yang,Jiang Mingjun,Liu Ju,Chen Ye
Aim: An active-passive dual-targeting gambogic acid HPMA Copolymer Coupling drug system with high efficiency, low toxicity and high selectivity was constructed. Methods: The gambogic acid HPMA copolymer coupling drug system was constructed and its structure was characterized. The
cytotoxicity of gambogic acid HPMA copolymer was detected by MTT assay. The pharmacokinetics of gambogic acid HPMA copolymer was evaluated in mice. Targetability of gambogic acid HPMA copolymer was evaluated by tissue distribution experiment. The in vitro antitumor activity of gambogic acid
HPMA copolymer was evaluated by pharmacodynamics experiment in mice. Results: Two copolymers of gambogic acid HPMA were successfully prepared. The copolymers showed reduced cytotoxicity and a certain sustained release effect and targeting property. In vivo pharmacodynamic experiments
also showed better anti-tumor effects than GA. Discussion: In this study, gambogic acid was combined with HPMA polymer and the targeting molecule D-galactose/folic acid to form a polymer micelle with high efficiency, low toxicity and high selectivity for active-passive dual targeting.
The construction of the drug system provides new ideas for future formulation research and development.
研究领域:
药学
·
肿瘤学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2019
·Vol. 15
·期 8
·1688-1700
·
IF 0
Zhou Minglu,Tang Manling,Zhang Hu,Luo Kui,Huang Yuan
The balance between systemic toxicity and circulation time for a polymeric nanocarrier to deliver antitumor drugs has been trialed. A new approach to break the balance was proposed in this study by significantly improving its biosafety and prolonging the circulation time, hence, to
enhance its anti-tumor efficacy. A matrix metalloproteinases (MMPs)-sensitive peptide (PVGLIGK) was introduced to cross-link the N-(2-hydroxypropyl) methylacrylamide polymer-doxorubicin conjugates (HPMA-Dox) conjugate to construct a nano-size polymeric nanocarrier-Dox assembly (PMD) with a
molecular weight (MW) of 73 kDa and this modification has resulted in a prolonged circulation time (a half-time of 20.1 h) and enhanced accumulation of PMD at the tumor site, while negligible systemic toxicity and excellent biocompatibility were displayed after injection of PMD into the mice.
The cross-linked nanoassembly was unpacking in the presence of MMPs in the extracellular microenvironment, and the conjugated Dox was released from the nanoassembly in the lysosome/endosome due to an intracellular low pH microenvironment. The released Dox from PMD inhibited tumor cells very
efficiently with a tumor growth inhibition of around 70%. The outstanding performance of the dual stimuli-responsive biodegradable polymeric nanocarriers may open a door for other hydrophobic anti-tumor drugs.
研究领域:
药学
·
肿瘤学
·
生物材料学
✓ 已验证
DOI
PubMed
RSC Advances
·
2015
·Vol. 5
·期 19
·14858-14870
·
IF 3.84
Qingqing Yang,Lian Li,Xi Zhu,Wei Sun,Zhou Zhou,Yuan Huang
Thanks to the enhanced cancer cell affinity, modification of polymeric drug carriers with an active targeting ligand has been one of the most effective strategies to achieve better therapeutic efficacy. However, hydrophobic ligands (e.g. folate), when conjugated to hydrophilic carriers, encounter the problem of reduced targeting effectiveness due to the fact that the ligand may be buried inside the carrier. In the present study, we studied the impact of the hydrophilic polymer structure on the targeting efficiency of the conjugated folate (FA). After modification with folate, the linear N-(2-hydroxypropyl)-methacrylamide (HPMA) polymer (P-FA, 27.3 kDa) exhibited a neutral surface charge (1.5 mV), while the graft HPMA polymer (GP-FA, 117.4 kDa) possessed a mild negative charge (−7.2 mV), which suggests different exposure levels of negatively charged folate on the surface of P-FA and GP-FA. Notably, on folate receptor positive MCF-7 cells, P-FA exhibited comparable cell uptake with the unmodified linear polymer, whereas GP-FA resulted in 2-fold higher cell internalization over the untargeted graft polymer. Meanwhile, the involvement of folate receptor mediated endocytosis and augmented folate binding affinity of GP-FA were observed in comparison with P-FA. Moreover, GP-FA exhibited significantly enhanced tumor accumulation relative to GP, while marginally improved tumor accumulation was observed for P-FA compared with P. In summary, the structure of the hydrophilic polymer plays a vital role in the targeting efficiency of the conjugated hydrophobic ligand.
研究领域:
药学
·
聚合物化学
·
癌症研究
✓ 已验证
DOI
高影响因子
Polymer Chemistry
·
2016
·Vol. 7
·期 13
·2372-2380
·
IF 5.687
Jianbo Tan,Yuhao Bai,Xuechao Zhang,Li Zhang
The photoinitiated polymerization-induced self-assembly (photo-PISA) of 2-hydroxypropyl methacrylate (HPMA) is conducted in water by using poly(poly(ethylene glycol) methyl ether methacrylate) (PPEGMA) based macro-RAFT agents. Polymerizations were carried out at room temperature via exposure to visible light irradiation, and quantitative monomer conversions (>99%) were achieved within 30 min of visible light irradiation. A remarkably diverse set of complex morphologies (spheres, worms, and vesicles) have been prepared by aqueous photo-PISA under mild conditions (water medium, room temperature, and visible light). The morphology of nano-objects can be tuned by changing the reaction parameters (e.g. degree of polymerization, solids concentration), and two detailed phase diagrams were constructed. The polymerization can be activated or deactivated by a simple “ON/OFF” switch of the light source. A thermo-responsive behavior of PPEGMA14-PHPMA200 nanoparticles prepared at 15% w/w was investigated by changing the temperature from 25 °C to 4 °C.
研究领域:
材料科学
·
化学工程
·
高分子化学
✓ 已验证
产品关联
DOI
高影响因子
MINERALS ENGINEERING
·
2024
·
IF 4.9
Jiajun Liu,Guofan Zhang,Binbin Li,Xinya Fu,Sen Li
In this study, we aimed to address the problem of fine-grained serpentine forming “slime coating” on the surface of pyrite, which deteriorates the flotation of pyrite, by systematically investigating the effects of HPMA on the separation of pyrite and serpentine, as well as the underlying mechanism. The flotation results indicated that the recovery of pyrite deteriorated by serpentine was significantly increased and reached 90 % by adding 30 mg/L of HPMA at pH 9.00. The total organic carbon (TOC) test and zeta potential test results revealed that the adsorption of HPMA on serpentine was much stronger than that on pyrite. The adsorption behavior was confirmed by X-ray photoelectron spectroscopy (XPS) analyses, which demonstrated that HPMA could chelate with positively charged Mg ions on the surface of serpentine, resulting in a significant change in the surface charge of serpentine to a negative state. The positive effect of HPMA on pyrite flotation was visualized by a scanning electron microscope-energy dispersive spectroscopy (SEM-EDS) analyzer and characterized by the major elemental content. As a result of the addition of HPMA, the surface charge of serpentine was changed from positive to negative, which resulted in the disruption of co-cohesion between serpentine and pyrite. This result enhanced the natural floatability of pyrite and the adsorption of collector potassium amyl xanthate (PAX) on pyrite, thus achieving the selective flotation between pyrite and serpentine.
研究领域:
矿物加工工程
·
环境科学
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DOI
高影响因子
Pigment & Resin Technology
·
2022
·Vol. 53
·期 2
·145-153
·
IF 1.126
Wanting Zhao,Lijun Chen
PurposeSelf-crosslinked long fluorocarbon acrylate polymer latex has good hydrophobic and oleophobicity, weather resistance, aging resistance, stability and other excellent properties, which make the polymer be widely used in coatings, dyes, adhesives and other products. The purpose of this study is to prepare self-crosslinked long fluorocarbon acrylate polymer latex via semi-continuous seeded emulsion technology and carry out comparative study on two different cross-linked monomers.Design/methodology/approachMethyl methacrylate (MMA) and butyl acrylate (BA) were used as the main monomers, dodecafluoroheptyl methacrylate (DFMA) as the fluoromonomer, hydroxypropyl methacrylate (HPMA) andN-methylol acrylamide (NMA) as cross-linked monomers, and 1-allyloxy-3–(4-nonylphenol)-2-propanol polyoxyethylene (10) ether (ANPEO10) and 1-allyloxy-3–(4-nonylphenol)-2-propanol polyoxyethylene (10) ether ammonium sulfate (DNS-86) as compound emulsifiers via the semicontinuous-seeded emulsion polymerization.FindingsThe properties of the polymer emulsions, which are prepared with two different cross-linked monomers, are compared and discussed, and it is concluded that HPMA is more suitable for the preparation of self-crosslinked polymer emulsions. The formula of the polymer latex is ANPEO10: DNS-86 = 1:1, and the mass ratio of the monomers used in the polymer is MMA: BA: DFMA: HPMA = 14.40:14.40:0.60:0.60.Practical implicationsSelf-crosslinked long fluorocarbon acrylate polymer latex can be used in many fields such as coatings, dyes, adhesives and other products.Originality/valueThe self-crosslinked long fluorocarbon acrylate polymer latex is prepared by mixing the nonionic emulsifier ANPEO10 and the anionic emulsifier DNS-86 when potassium persulfate is used as the thermal decomposition initiator and the semicontinuous-seeded emulsion technology is adopted and the comparative study on two different cross-linked monomer is carried out, which is not reported in the open literatures.
研究领域:
材料科学
·
化学工程
✓ 已验证
DOI
高影响因子
CHEMICAL PAPERS
·
2021
·Vol. 75
·期 10
·5561-5569
·
IF 2.097
Shao Tantan,Gong Yilu,Chen Xiaolong,Chen Lijun
Novel self-crosslinking long fluorocarbon acrylate polymer latex has been successfully prepared by semi-continuous seeded emulsion polymerization with methyl methacrylate(MMA), butyl acrylate (BA), dodecafluoroheptyl methacrylate (DFMA) and hydroxypropyl methacrylate(HPMA) as main monomers, 10-undecylenic acid (10-UA) and diallyl phthalate (DAP) as functional monomers. During the latex polymerization, the monomers were emulsified by the mixed surfactants of nonionic surfactant alcohol ether glycoside (AEG) and anionic surfactant sodium dodecylbenzene sulfonate (SDBS), and initiated by potassium persulfate (KPS). The resultant latex showed excellent properties. The chemical composition of latex was determined with Fourier transform infrared spectrum (FTIR) and the glass transition temperature (Tg) of polymer was detected by differential scanning calorimetry (DSC) and the water repellency of the prepared film was measured by water contact angle measurement (WCA). The reaction conditions were optimized and obtained as follows: the optimal monomer dosage was MMA: BA: DFMA: HPMA = 12.75:12.75:0.9:1.2, the amount of 10-UA and DAP was both 4% of all monomers, the dosage of AEG: SDBS was 5% (1:1) and KPS was 0.5%, respectively. The result indicated that the conversion of the mixed monomers was more than 98% and the coagulation was less than 1% and the resultant latex also had the outstanding appearance and latex performance.
研究领域:
材料科学
·
高分子化学
✓ 已验证
DOI
高影响因子
Nanoscale
·
2016
·Vol. 9
·期 4
·1547-1558
·
IF 7.76
Qingqing Yang,Lei Wu,Lian Li,Zhou Zhou,Yuan Huang
Co-delivery of multiple agents via nanocarriers is of great interest in cancer therapy, but subcellular delivery to the corresponding site of action remains challenging. Here we report a smart nanovehicle which enables two different site-oriented payloads to reach their targeted organelles based on stimulus-responsive release and nucleus-targeted modification. First, all trans retinoic acid (RA) conjugated camptothecin (RA–CPT) was loaded in a polyhedral oligomericsilsesquioxane (POSS)-based core; docetaxel (DTX) was grafted on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers. The POSS core grafted with semitelechelic HPMA copolymers then self-assembled into micelles. Once internalized into the cell, the two drugs were unleashed environment-responsively, and nuclear targeted RA remarkably facilitated the nuclear transport of CPT. Compared with single drug-loaded micelles, the dual drug-loaded platform showed superior synergic cytotoxicity, which was further strengthened by the involvement of RA. The ability to induce DNA damage and apoptosis was also enhanced by nucleus-targeted modification. Finally, dual drug-loaded micelles exhibited much better in vivo tumor inhibition (87.1%) and less systemic toxicity than the combination of single drug-loaded systems or the dual drug-loaded micelles without RA. Therefore, our study provides a novel “one platform, two targets” strategy in combinatory anti-cancer therapy.
研究领域:
纳米技术
·
药学
·
肿瘤学
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
POLYMER
·
2018
·
IF 3.483
Jun He,Dongdong Liu,Jianbo Tan,Li Zhang
We report a novel blue light initiated aqueous reversible addition–fragmentation chain transfer (RAFT) dispersion polymerization of 2-hydroxypropyl methacrylate (HPMA) with a poly (glycerol monomethacrylate) homopolymer as the macro-RAFT agent and sodium bis(acyl)phosphane oxide (SBAPO) as the photoinitiator . High monomer conversions were achieved within 1 h of blue light irradiation . Taking advantage of the temperature-insensitive feature of photoinitiator , the effect of reaction temperature on the blue light initiated aqueous RAFT dispersion polymerization was studied in detail. A new morphological phase diagram was constructed for the first time by changing the degree of polymerization (DP) of the core-forming block and the reaction temperature. Moreover, a typical morphological phase diagram for the blue light initiated aqueous RAFT dispersion polymerization at 70 °C was also built and various morphologies have been prepared. Effect of wavelength of light (405 and 465 nm) on copolymer compositions and morphologies was studied. Finally, a fully one-pot blue light initiated aqueous RAFT polymerization was developed for the synthesis of various diblock copolymer nano-objects.
研究领域:
高分子化学
·
光化学
·
材料科学
·
纳米技术
·
高分子工程
✓ 已验证
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Qiyi Feng,Jie Chen,Jinxing Huang,Xiaojie Li,Xinyi Liu,Chunxiu Xiao,Xiuli Zheng,Xuanming Chen,Jue Li,Zhongwei Gu,Kui Luo,Kai Xiao,Weimin Li
Cancer stem cells (CSCs) have been demonstrated to be involved in tumor initiation and relapse, and the presence of CSCs in the tumor tissue often leads to therapeutic failure. BBI608 has been identified to eliminate CSCs by inhibiting signal transducer and activator of transcription 3 (STAT3). In this study, we confirm that BBI608 can efficiently suppress the proliferation and migration of non-small cell lung cancer (NSCLC) cells, and specifically kill the stemness-high population in chemoresistant NSCLC cells. To improve its bioavailability and tumor accumulation, BBI608 is successfully encapsulated into redox-responsive PEGylated branched N-(2-hydroxypropyl) methacrylamide (HPMA)-deoxy cholic acid (DA) polymeric nanoparticles (BBI608-SS-NPs). The BBI608-SS-NPs can release the drug in response to high concentrations of intracellular glutathione, and exhibit cytotoxicity against lung cancer cells and CSCs comparable to the free drug BBI608. Furthermore, the BBI608-SS-NPs preferentially accumulate in tumor sites, resulting in a superior anti-tumor efficacy in both cisplatin-resistant cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models of NSCLC. Mechanistic studies demonstrate that BBI608-SS-NPs not only directly inhibit the downstream genes of the STAT3 pathway, but also indirectly inhibit the Wnt pathway. Overall, this stimuli-responsive polymeric nanoformulation of BBI608 shows great potential in the treatment of chemoresistant NSCLC by targeting CSCs.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2015
·
IF 6.723
Qingqing Yang,Yang Yang,Lian Li,Wei Sun,Xi Zhu,Yuan Huang
To improve the therapeutic efficacy of anticancer combination therapy, we designed a nanoplatform based on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers that allows covalent bonding of two chemotherapeutics acting via different anticancer mechanisms and that can enter target cells by receptor-mediated endocytosis. Doxorubicin (DOX) was covalently conjugated to a nanosized HPMA copolymer using a pH-sensitive hydrazone bond and 5-fluorouracil (5-Fu) was conjugated to the same backbone using an enzymatically degradable oligopeptide Gly-Phe-Leu-Gly sequence. Then, the conjugate was decorated with galectin-3 targeting peptide G3-C12 [P-(G3-C12)-DOX-Fu]. The two drugs showed similar in vitro release profiles, suggesting that they may be able to work synergistically in the codelivery system. In galectin-3 overexpressed PC-3 human prostate carcinoma cells, P-(G3-C12)-DOX-Fu surprisingly exhibited comparable cytotoxicity to free DOX at high concentration by increasing cell internalization and exerting synergistic genotoxic effects of cell cycle arrest, caspase-3 activation, and DNA damage. In mice bearing PC-3 tumor xenografts, the use of tumor-targeting ligand substantially enhanced the intracellular delivery of P-(G3-C12)-DOX-Fu in tumors. The targeted dual drug-loaded conjugate inhibited tumor growth to a greater extent (tumor inhibition of 81.6%) than did nontargeted P-DOX-Fu (71.2%), P-DOX (63%), DOX·HCl (40.5%), P-Fu (32.0%), or 5-Fu (14.6%), without inducing any obvious side effects. These results demonstrate the potential of synergistic combination therapy using targeted nanocarriers for efficient treatment of prostate cancer.
研究领域:
纳米技术
·
药学
·
肿瘤学
·
分子生物学
·
药物递送系统
✓ 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）