Acta Biomaterialia
·
2022
·
IF 10.633
Fangjun Liu,Dun Wang,Miao Zhang,Liwei Ma,Cui-Yun Yu,Hua Wei
Synthesis of polyfluorene (PF) based theranostic amphiphilic copolymers with simultaneously high drug loading efficiency and tumor microenvironment-specific responsiveness for promoted intracellular drug release and enhanced cancer therapy has been rarely reported likely due to the lack of efficient synthetic approaches to integrate these desirable properties. In this work, we recorded the successful preparation of well-defined theranostic amphiliphilic bottlebrush copolymers composing of fluorescent backbone of PF and tunable enzyme-degradable side chains of polytyrosine (PTyr) and POEGMA by integrating Suzuki coupling , NCA ROP and ATRP techniques. Notably, the resulting copolymer, PF 25 - g -(PTyr 26 - b -(POEGMA 28 ) 2 (P 4 ) with two branched POEGMA brushes tethered to one PTyr termini for each unit could form steady unimolecular micelles with higher fluorescence quantum yield of 18.3% in aqueous and greater entrapment efficiency (EE) of 91.0% for DOX ascribed to the efficient π–π stacking interactions between PTyr blocks and drug molecules and the unique structure of branched hydrophilic brushes with a moderate chain length. DOX@P 4 micelles revealed visualization of intracellular trafficking and accelerated drug release due to the enzyme-triggered degradation of PTyr blocks with proteinase K and subsequent deshielding of POEGMA corona for micelle destruction. In vitro and In vivo animal study further verified the intensive therapeutic efficiency with attenuated systematic toxicity. Taken together, we provided a universal strategy toward multifunctional polymeric delivery vehicles based on conjugated PF and biocompatible and degradable polypeptide by integratied Suzuki coupling and NCA ROP, and identified the branched structure of hydrophilic brushes for better performance of bottlebrush copolymers-based micelles for drug delivery applications. Statement of significance Synthesis of polyfluorene (PF)-based theranostic amphiphilic copolymers with simultaneously high drug loading efficiency and tumor microenvironment-specific responsiveness for promoted intracellular drug release and enhanced cancer therapy has been rarely reported likely due to the lack of efficient synthetic approaches to integrate these desirable properties. We reported herein successful preparation of enzyme-responsive theranostic amphiliphilic bottlebrush copolymers with simultaneously high drug loading efficiency and tumor microenvironment-specific responsiveness for enhanced chemotherapy in vivo . This study therefore not only developed a universal strategy for the construction of multifunction polymeric vehicles based on the conjugated polymer of PF and degradable polypeptide by integrated Suzuki coupling and NCA ROP, but also emphasized the better stability of micelles endowed by the branched hydrophilic brushes than linear ones.
研究领域:
高分子化学
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生物医学工程
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癌症治疗
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
·
2019
·Vol. 26
·期 24
·25107-25116
·
IF 2.914
Liu Guanghua,Lin Guanquan,Lin Xida,Zhou Hongjun,Chen Huayao,Hao Li,Zhou Xinhua
The overdosage use of pesticide was harmful to the environment and human health, which was mainly caused by the low utilization rate of the pesticide. However, the pesticide microcapsule with sustained-release and stimulating response properties could effectively solve this problem. Preparation of carboxymethyl cellulose grafting dimethyldiallylammonium chloride (CMC-g-PDMDAAC) through grafting polymerization and trapping as well as encapsulation of avermectin (AVM) via electrostatic interactions resulted in the formation of AVM/CMC-g-PDMDAAC microcapsules. The results showed that the particle size was 200~300 nm. The encapsulation efficiency was as high as 72.06%. Furthermore, the remaining rate of encapsulated AVM increased from 50.0 to 81.60% after UV irradiation for 359 min. The microcapsules exhibited significant enzyme and pH stimuli responsiveness. Finally, CMC-g-PDMDAAC had no significant difference effect on the toxicity of AVM, AVM could be found, and DMDAAC featured a synergistic effect on the toxicological effects of AVM.
Graphical abstract
研究领域:
农药科学
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材料科学
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环境科学
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产品关联
DOI
PubMed
高影响因子
Polymers
·
2022
·Vol. 14
·期 21
·4515
·
IF 4.967
Jiankun Xu,Shanmeng Lin,Hao Hu,Qi Xing,Jin Geng
Bufalin (buf) has poor solubility in aqueous solution, poor tumor targeting, and many non-specific toxic and side effects. The advantages of high-molecular-weight polymer conjugates are that they can improve the water solubility of buf, prolong plasma half-life, and reduce non-specific toxicity. A novel water-soluble polymer–drug conjugate with buf and fluorescein pendants was prepared by the combination of reversible addition-fragmentation transfer (RAFT) polymerization and click chemistry. Its anticancer performance and cellular uptake behavior against liver cancer were investigated in vitro. The polymer–buf conjugates exhibit controlled release and tumor-targeting capabilities, showing promise for clinical applications.Keywords:polymer–drug conjugate;liver cancer;esterase responsive;bufalin
研究领域:
药学
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肿瘤学
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DOI
PubMed
高影响因子
ACS Agricultural Science & Technology
·
2024
·
IF 2.3
Leiyu Yang,Yifan Luo,Yapeng Chen,Sanyan Wang,Huashan Wang,Meiyi Wang
Fomesafen serves as a widely employed selective herbicide for addressing broadleaf weeds, but the short duration of efficacy limits utilization efficiency. There exists an exigent requirement to extend its efficacy through controlled release mechanisms. Fomesafen@SiO2-starch microspheres with α-amylase responsiveness were synthesized through the direct binding of drug-loaded silica microspheres and modified starch. This fabrication method capitalizes on the enzymatic degradation potential of the outer starch layer by amylase. In contrast with earlier analogous structures that exhibited inferior drug loading efficacy, the prepared fomesafen@SiO2-starch microspheres demonstrated a significantly enhanced drug loading capacity of up to 35.7%. Furthermore, in comparison to fomesafen technical, the prepared fomesafen@SiO2-starch microspheres exhibited a notable capacity to mitigate the photolysis of fomesafen through the utilization of the starch outer layer. Additionally, the fomesafen@SiO2-starch microspheres demonstrated favorable wettability and adhesive properties. At the recommended dosage, the herbicidal efficacy of fomesafen@SiO2-starch microspheres against Brassica napus L. and Portulaca oleracea L. over 14 days was observed to be comparable to that of the fomesafen technical, concurrently exhibiting a degree of sustained release. These findings underscore the potential of microspheres in regulating the release of fomesafen, thereby presenting a promising avenue for the development of sustainable drug delivery systems in agriculture.
研究领域:
农业科学
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材料科学
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植物保护学
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产品关联
DOI
高影响因子
JOURNAL OF POLYMER SCIENCE
·
2021
·Vol. 59
·期 17
·1958-1971
·
IF 0
Guoyang Qin,Cong Hu,Yanfen Jiang,Shuqi Dong,Li Liu,Hanying Zhao
We report the synthesis of pH- and enzyme-responsive amphiphilic diblock copolymers through reversible addition-fragmentation chain transfer polymerization of a lysine-derived methacrylate monomer comprising p -nitrobenzyl carbamate ( p NBC) functionality using a poly(ethylene glycol)-modified macro-chain transfer agent. Depending on the hydrophobic block length, the diblock copolymers self-assemble to form spherical micelles, wormlike micelles, and bilayered vesicles in the aqueous solution. The responsive behaviors of the polymeric vesicles to pH, enzyme, and light are investigated in detail. As the pH lowers to pH 5.0, the polymeric vesicles undergo a morphological transition from vesicles to spherical micelles. In the presence of nitroreductase and a cofactor NADH, the decomposition of p NBC releases the ε-NH 2 of the lysine moiety and hence induces the generation of the vesicles with crosslinked membranes at pH 7.4. Moreover, owing to the degradation of p NBC moiety under UV irradiation, the polymeric vesicles also demonstrate a photo-responsive feature. As the irradiation time prolongs, it is observed a light-triggered morphological transition from vesicles to wormlike micelles with network-like structures. Graphical
研究领域:
材料科学
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生物化学
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纳米医学
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产品关联
DOI
ACS Applied Materials & Interfaces
·
2014
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IF 5.9
Guilong Zhang,Minglei Yang,Dongqing Cai,Kang Zheng,Xin Zhang,Lifang Wu,Zhengyan Wu
An efficient enzyme-responsive controlled release carrier system was successfully fabricated using single-stranded DNA encapsulated functional mesoporous silica nanoparticles. Mesoporous silica nanoparticles were initially fabricated through hydrolysis of tetraethyl orthosilicate (TEOS) in cetyltrimethylammonium chloride (CTAC) solution, and the surface of nanoparticles could be encapsulated with single-stranded DNA. This nanomaterial has excellent bioactivity and its hydrolysate cannot cause damage to normal cell, thus the biocompatibility of the nanomaterial is improved. In addition, this nanomaterial showed an excellent drug release performance when loaded with drugs, which would be helpful to increase the treatment efficiency and decrease side effects of drugs.
研究领域:
材料科学
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生物医学工程
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纳米技术
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2018
·
IF 3.997
Jie Zhang,Xiuli Ren,Xiaohan Tian,Peng Zhang,Zhenhua Chen,Xun Hu,Xifan Mei
Developing safe and effective stimuli-responsive nanocarriers is very important for tumor chemotherapy. In this work, bovine serum albumin (BSA) and green tea polyphenol (TP) were used to prepare glutathione (GSH) and enzyme (trypsin) responsive nanocarriers for doxorubicin (DOX). These nanocarriers were further modified with folate, briefly named as DOX@BSA-TP-FA NSs. The diameter of nanocarriers was about 220 nm. The DOX loading efficiency and loading amount were 86.4% and 23.5 wt%, respectively. The cellular uptake, apoptosis, and GSH and trypsin responsive release properties of these nanocarriers were investigated.
研究领域:
生物医学工程
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肿瘤学
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药剂学
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产品关联
DOI
PubMed
高影响因子
GREEN CHEMISTRY
·
2022
·Vol. 24
·期 9
·3667-3676
·
IF 11.034
Bin He,Pengbing Chang,Sufeng Zhang,Xing Zhu
Encapsulating toxic insecticides in a system to reduce their impact on non-target organisms and the environment, thereby enhancing pest control specificity and ensuring human safety, is important but there exist numerous challenges. In the present study, a cellulase-responsive carrier for the controlled release of avermectin (AVM) was prepared based on poly (ethylene glycol) diacrylate (PEGDA)-anchored porous regenerated cellulose microspheres (RCMs), with the goal of realizing their application as insecticide carriers for enzyme-mediated controlled release. Since the as-prepared RCMs showed an excellent loading ability for AVM, biocompatible PEGDA was used to block cellulose micropores and prevent the leakage of AVM. Thus, human safety was ensured. The results show that the cell viability was maintained at 90% in the AVM-loaded microspheres group after 5 days while it was only 70% in the free AVM group, indicating that the system is considerably safer for the human body. Furthermore, the AVM-loaded microspheres group showed excellent toxicological properties against Plutella xylostella and mole cricket. The lethality rates against the two target insects were 90 and 82%, respectively, at a concentration of 60 mg L−1, indicating the high efficacy of the insecticide. This work provides a feasible strategy to eliminate the toxic side effects of insecticides, which is of great significance to agricultural safety.
研究领域:
农业科学
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生物材料学
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环境科学
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DOI
高影响因子
FERROELECTRICS
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2021
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IF 0.62
Feng Wang,Fang-Yuan Lv,Kui-Long Liu,Zhi-Hao Li,Shu Niu,Yun-Yi Zhang,Hai-Lin Cong,You-Qing Shen,Bing Yu
A MoS2 nanosheets drug delivery system with photothermal conversion ability was synthesized. The drug loading content of the synthesized was as high as 24.5%. The drug HCPT was modified by lipoic acid (LA) and connected onto MoS2 nanosheets through S-Mo bond, which is more stable than physical adsorption. Due to the ester bond between HCPT and MoS2 nanosheets, the drug delivery system could responsively release HCPT when exposed to esterase.
研究领域:
材料科学与工程
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生物医学工程
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药剂学
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产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2019
·
IF 3.973
Hongjian Wen,Hongjun Zhou,Li Hao,Huayao Chen,Hua Xu,Xinhua Zhou
Novel enzyme cum pH dual-responsive microcapsule were prepared with an aim to enhance the utilization of pesticides and reduce environmental pollution. The synthetic procedure involved the introduction of urea bonds by forming a covalent bond between isocyanate–functionalized polydopamine (PDA) microcapsules and polyethyleneimine (PEI). The prepared AVM@PDA-IPTS-PEI microcapsules could effectively protect avermectin (AVM) from ultraviolet radiation, and thus decelerate the decomposition rate; the cumulative release showed positive correlations with pH and the urease activity. The AVM release rate was highest at pH 10. At pH 7, the release rate was enhanced after addition of urease, showing improved urease-responsive property under neutral or weak base condition. Especially at pH 7 in presence of urease, the release behavior was in agreement with the Logistic model and able to describe the S-shaped/sigmoidal release profiles, whereas Korsmeyer–Peppas model was better suited in the absence of urease, as the value of K 1 was smaller than 0.45, suggesting that the behavior was controlled by Fick’s diffusion. AVM@PDA-IPTS-PEI displayed better adhesion property than AVM, and the microcapsule ameliorated foliage wettability. AVM@PDA-IPTS-PEI exhibited the insecticidal property similarly with AVM, which can be used for reducing the applied quantity of pesticides and improving their efficacy.
研究领域:
农业科学
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材料科学
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环境科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-20
·
IF 12.6
Wu Can,Zhang Xiao Wei,Wang Manman,Sun Jinpan,Chen Jianfei,Guan Yanbin,Pang Xin
Chemotherapy remains an effective treatment for colon cancer but is hampered by its limited response rate. Bioactive peptides, marked with intracellular transformations, have been reported as an effective approach to boosting chemotherapeutic activity. Herein, a promising trypsin-responsive bioactive peptide-based nanodrug is constructed, which could significantly prolong the drug retention time in vivo by cascading transformations and improve chemotherapeutic efficacy. Initially, 1-Pept co-assembles with Dox into a few nanofibers called 1-Pept/Dox NFs, inducing an enhanced cellular uptake via caveolae-mediated endocytosis by avoiding lysosomal degradation and further promoting perinuclear transportation, thus enlarging the drug efficacy in target areas. After nanofiber disassembly, the released 1-Pept converts into Pept under the catalysis of intracellular overexpressed trypsin, which then reassembles into denser Pept NFs, inducing a cascade of effects including disruption of the cytoskeleton, mitochondrial dysfunction, and activation of caspase-3. By the synergism of Pept NFs and Dox, caspase-3 can be further activated, and cause greater damage to nuclear, thereby leading to tumor ablation. As the first example of employing trypsin-mediated nanodrugs with cascading transformations to promote chemotherapeutic activity, this work promises a strategy for novel therapies for efficiently combating colon cancer. Graphical
研究领域:
药理学
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肿瘤学
·
纳米医学
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产品关联
DOI
PubMed
高影响因子
Polymer Chemistry
·
2017
·Vol. 9
·期 4
·438-449
·
IF 5.375
Zhen Zhang,Yongcun Zhou,Zhuxian Zhou,Ying Piao,Nagendra Kalva,Xiangrui Liu,Jianbin Tang,Youqing Shen
Stimuli-responsive dendrimers are attractive nanocarriers for cancer drug delivery due to their inherent structure, biodegradability and precise control of release of a payload in response to specific triggers. However, the efficient and precise synthesis of such dendrimers with site-specific responsiveness is challenging. We report an efficient synthesis of enzyme-responsive phosphoramidate (PAD) dendrimers from a pair of monomers using click and click-like reactions. These dendrimers were stable in phosphate buffered saline (PBS) but degradable in the presence of phospholipase C (PLC) that was overexpressed on cancer cells. The surface modification of the dendrimers with zwitterionic groups (2-methacryloyloxyethyl phosphorylcholine, MPC) greatly reduced the nonspecific binding of the plasma proteins and therefore enhanced blood circulation time. The PAD-MPC dendrimers easily encapsulated hydrophobic drugs such as doxorubicin (DOX). The DOX-loaded PAD-MPC (PAD-MPC/DOX) showed PLC-responsive drug release and efficient delivery of DOX to cancer cells by overcoming multidrug resistance. The PLC-responsive PAD-MPC/DOX was highly toxic to cancer cells and less effective on normal cells. The PAD-MPC/DOX showed improved therapeutic effects and reduced toxicity in athymic nude mice bearing xenografts of MCF-7/ADR breast cancer.
研究领域:
药学
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生物医学工程
·
肿瘤学
✓ 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）