INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2022
·Vol. 23
·期 17
·9698
·
IF 6.208
Dong Wan,Yujun Liu,Xinhao Guo,Jianxin Zhang,Jie Pan
To endow the polymeric prodrug with smart properties through a safe and simple method, matrix metalloproteinase (MMPs) responsive peptide GPLGVRGDG was introduced into the block copolymer to prepare TPGS3350-GPLGVRGDG-DOX&DOX micelles, where TPGS3350is D-α-tocopheryl polyethylene glycol 3350 succinate. During the doxorubicin delivery, the cleavage of the peptide chain triggers de-PEGylation, and the remaining VRGDG sequence was retained on the surface of the micelles, which can act as a ligand to facilitate cell uptake. Moreover, the cytotoxicity of TPGS3350-GPLGVRGDG-DOX&DOX micelles against 4T1 cells was significantly improved, compared with TPGS3350-GPLGVRG-DOX&DOX micelles and TPGS3350-DOX&DOX micelles. During in vivo studies, TPGS3350-GPLGVRGDG-DOX&DOX micelles exhibited good anticancer efficacy with long circulation in the body and more efficient accumulation at the tumor site. Therefore, TPGS3350-GPLGVRGDG-DOX&DOX micelles have improved antitumor activity and reduced toxic side effects. This work opens new potential for exploring the strategy of drug delivery in clinical applications.Keywords:drug delivery;peptide;micelles
研究领域:
药学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
·
IF 5.2
Xiaoyu Hu,Jun Liu,Qingrong Wang,Qiongkun Hu,Hao Sun,Shi Wang,Yu Zhao,Liwei Gu,Jianying Shen,Qinghe Zhao,Feng Sui,Hai Ma
Gemcitabine, a chemotherapeutic agent widely approved for treating various cancers, faces significant clinical challenges, including drug resistance and poor tumor selectivity. To address the limitation of inadequate tumor targeting, a peptide chain was developed to specifically bind to colon cancer cells and conjugated to gemcitabine via aldehyde–amine condensation. This study aimed to exploit the oncogenic activity of the multifunctional protein α-Enolase (ENO1). The therapeutic efficacy of gemcitabine conjugated with the ENO1-targeting peptide (GCB-P) was evaluated through in vitro and in vivo experiments. Cytotoxicity assays and protein blotting analyses were performed on cell lines, including NCM-460, HCT116 and SW620. GCB-P exhibited significantly enhanced selectivity and potency against colon cancer cells compared to gemcitabine alone, with minimal cytotoxicity to normal colorectal cells. In addition, GCB-P demonstrated superior tumor-selective accumulation and release at the tumor site, as evidenced by in vivo metabolic analyses. These findings underscore the potential of GCB-P as an effective colon cancer treatment with reduced off-target toxicity. Furthermore, GCB-P displayed acid-responsive properties, facilitating precise delivery to tumor sites with the aid of homing peptides. These results highlight the promise of ENO1-targeted peptide modification for gemcitabine in developing targeted drug delivery systems for colon cancer.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Polymers
·
2019
·Vol. 11
·期 3
·511
·
IF 3.164
Jingjie Feng,Weiqiu Wen,Yong-Guang Jia,Sa Liu,Jianwei Guo
One of the most famous anticancer drugs, paclitaxel (PTX), has often been used in drug controlled-release studies. The polymers derived from bio-compound bile acids and degradable poly(ε-caprolactone) (PCL) form a reservoir and have been used as a drug delivery system with great advantages. Herein, we grafted poly(N,N-diethylaminoethyl methacrylate) and poly(poly(ethylene glycol) methyl ether methacrylate) into the bile acid-derived three-armed macroinitiator CA-(PCL)3, resulting in the amphiphilic block copolymers CA-(PCL-b-PDEAEMA-b-PPEGMA)3. These pH-responsive three-armed block copolymers self-assembled into micelles in aqueous solution and PTX was encapsulated into the micellar core to form PTX-loaded micelles with a drug loading of 29.92 wt %. The micelles were stable in PBS at pH 7.4 and showed a pH-triggered release behavior of PTX under acidic environments, in which 55% of PTX was released at pH 5.0 in 80 h. These cholic acid-based functionalized three-armed block polymers present good biocompatibility, showing great potential for drug controlled-release.Keywords:cholic acid;pH-sensitive;PTX;drug delivery
研究领域:
生物材料学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Polymers
·
2023
·Vol. 15
·期 3
·564
·
IF 5
Huafen Wang,Huanhuan He,Jiaxiang Zhang,Juntao Liu,Yuwei Zhuang,Yuanyuan Yin,Zhiyong Ren,Yang Fu,Suqin He
Novel monomethoxy poly(ethylene glycol) (mPEG) modified hydroxylated tung oil (HTO), denoted asmPEG-HTO-mPEG, was designed and synthesized for drug delivery.mPEG-HTO-mPEG consists of a hydroxylated tung oil center joined by twomPEG blocks via a urethane linkage. The properties ofmPEG-HTO-mPEG were affected by the length of the mPEG chain. ThreemPEG with different molecular weights were used to preparemPEG-HTO-mPEG. The obtained threemPEG-HTO-mPEG polymers were characterized by nuclear magnetic resonance (NMR), Fourier transformation infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and gel permeation chromatography (GPC), respectively. Furthermore, the particle sizes ofmPEG-HTO-mPEG micelles were evaluated by dynamic light scattering (DLS) and transmission electron microscope (TEM). A critical aggregation concentration (CAC) ranged from 7.28 to 11.73 mg/L depending on the chain length of mPEG. The drug loading and release behaviors ofmPEG-HTO-mPEG were investigated using prednisone acetate as a model drug, and results indicated that hydrophobic prednisone acetate could be effectively loaded intomPEG-HTO-mPEG micelles and exhibited a long-term sustained release. Moreover, compared with HTO,mPEG-HTO-mPEG had no obvious cytotoxicity to HeLa and L929 cells. Therefore, monomethoxy poly(ethylene glycol) modified hydroxylated tung oilmPEG-HTO-mPEG may be a promising drug carrier.Keywords:hydroxylated tung oil;poly(ethylene glycol);drug delivery
研究领域:
材料科学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Hao Cheng,Zijun Jiang,Chenkai Sun,Zhen Wang,Guochen Han,Xin Chen,Tianyi Li,Zhechen Fan,Feng Zhang,Xiaoyu Yang,Lingyu Lv,Huaqing Zhang,Jianping Zhou,Yang Ding
The pro-metastatic potential of chemotherapy limits its therapeutic benefits against invasive cancer. Herein, a protein stabilized polymeric nanoparticle inspired relay drug delivery platform was developed to address post-chemotherapeutic metastasis. An ROS-responsive Phenylboronic acid (PBA)-Rich cationic polymer (RPP) bridges Doxorubicin (Dox) coordination and Snail-targeted siRNA (siSnail) compression, and natural apolipoprotein A-I (apoA-I) is attracted by surface electron-deficient PBA moieties for nanoparticle shaping, drug biostability, and tumour-penetration. The spatially-separated structure enables a timing-controlled relay drug delivery in tumour cells, where Dox gives a prior release phase by acidity, and RPP polymer is subsequently disintegrated by concentrated ROS for rapid siSnail liberation. In dual therapy, Dox pre-treatment upregulated pro-metastatic factors and aggravated metastasis, but subsequent liberation by siSnail silenced the central metastatic regulator of Epithelial-mesenchymal transition (EMT). The terminal nanoparticles exhibited advanced therapeutic efficacy, achieving primary tumour shrinkage (tumour weight inhibition, TWI of ~86.15%) and complete metastatic nodule elimination. This work promises to improve the clinical benefits of chemotherapy against invasive cancer.
研究领域:
肿瘤学
·
药剂学
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Tong Yu,Yeqing Wang,Yi Kong,Jianwei Wang,Hong Yun,Yunchao Wang,Fuqiang Hu,Zhongxin Zhu,Hong Yuan
Drug delivery system (DDS) is an important branch of pharmaceutics. Rational modification of the physicochemical properties of DDSs can further improve their targeting efficiency. Herein, a bionic DDS is reported for AKI that is scRNA-seq-guided, custom-designed, and prepared, targeting the Key Cell Subtype for Pathological Progression (KCS-PP) of acute kidney injury (AKI). Specifically, scRNA-seq is utilized to identify a specific renal tubular epithelial cell subtype (PTIs) as the KCS-PP for AKI from numerous cellular subtypes. Additionally, specific cell adhesion molecules (VCAM1 and ICAM1) are identified as the Targeting Drug Delivery Mediators (TDDMs) for PTIs from a list of 1000 marker genes of PTIs. Based on this progress, PTI-targeting bionic DDS, named BRNCs@AMMOs is custom-designed and prepared, and used them for AKI treatment in vitro and in vivo. In vitro, BRNCs@AMMOs shows that its adhesion ability in PTI model cells is 3.2 times that in normal cells. In vivo, 6 h after renal pelvis injection, the MFI of BRNCs@AMMOs-DiI in AKI kidneys is 3.7 times that of sham kidneys. The findings demonstrate that BRNCs@AMMOs exhibits prolonged retention in PTI model cells and AKI kidneys. Overall, the custom-designed and prepared PTI-targeting bionic DDS, may promote the customized design and preparation of DDSs for different diseases and targets, is reported.
研究领域:
药剂学
·
药物递送
·
分子医学
·
纳米技术
·
转化医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2023
·
IF 5.8
Yue Li,Junfang Ke,Hongxin Jia,Jungang Ren,Li Wang,Zhiqiang Zhang,Chen Wang
Based on the immune escape and homologous adhesion ability of cancer cells, a drug delivery system (DDS) could overcome the dilemma of immune clearance and non-specific binding by coating the cancer cell membrane (CCM). In this study, a biomimetic DDS based on CCM and poly lactic acid-glycolic acid (PLGA) nanoparticles was successfully constructed for tumor active and homologous targeting therapy. The doped CCM on the surface of the nanoparticle enabled the DDS to achieve immune escape and had an affinity for tumor tissues. The cellular uptake and in vivo distribution tests showed a superior cellular affinity of CCM coated PLGA nanoparticles (CCMNPs) than that of PLGA nanoparticles (PLGANPs). All of those results proved that CCMNPs endowed with drug-loaded nanoparticles had the abilities of immune escape and homologous targeting through the biological functional proteins retained on the coated CCM. In addition, the tumor inhibition rate of CCMNPs in tumor-bearing nude mice was 1.3 and 2.0-fold compared to PLGANPs and PTX injection, which showed the capacity to efficiently and accurately deliver drugs to cancer sites improved the therapeutic effect of tumor and achieved accurately targeted therapy.
研究领域:
药学
·
生物医学工程
·
肿瘤学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2025
·
IF 5.7
Niping Deng,Hao Lyu,Chengchen Guo
Gastrointestinal-retentive drug delivery devices represent a novel oral drug delivery approach capable of significantly enhancing patient compliance and improving local drug delivery efficiency compared to conventional oral formulations. However, developing gastrointestinal-retentive drug delivery devices with high retention capability based on compatible material systems presents significant challenges. Here, we introduce silk-based double-sided magnetic microneedles (SDMM) designed to facilitate targeted oral drug delivery with precise local retention in the gastrointestinal tract. The SDMM platform demonstrates robust mechanical properties, site-specific degradation, and compatibility with various capsule geometries, facilitating seamless integration into existing oral delivery systems. In vitro analyses demonstrate region-dependent drug release from the SDMM, supporting its potential for localized delivery of drugs in the gastrointestinal tract. The incorporation of iron oxide nanoparticles (IONPs) confers magnetically responsive targeting, offering a significant advantage over conventional approaches by ensuring precise retention and enhancing the targeted delivery potential under external magnetic fields. Notably, SDMM retains its positions under fluid flow rates up to 550 mL/min (stomach) and 400 mL/min (small intestine), respectively, underscoring its superior gastrointestinal retention. Furthermore, the in vivo retention experiments also showed significantly enhanced retention in the gastrointestinal tract, with the retention time of SDMM reaching almost 15 hours with magnet assistance, representing significantly prolonged retention compared to typical transit times in these regions. These findings establish SDMM as a promising platform for precise, efficient, and patient-friendly oral drug delivery.
研究领域:
药学
·
生物医学工程
·
药物递送系统
·
材料科学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2021
·
IF 5.875
Parbeen Singh,Yongli Chen,Deependra Tyagi,Li Wu,Xiaohong Ren,Jinglong Feng,Andrew Carrier,Tiangang Luan,Yongjun Tang,Jiwen Zhang,Xu Zhang
β-Cyclodextrin (β-CD) was grafted onto hyaluronic acid (HA) in a single step to generate a supramolecular biopolymer (HA-β-CD) that was explored for targeted drug delivery applications. Along with its excellent biocompatibility , the prepared HA-β-CD exhibits not only exceptionally high loading capacity for the model drugs doxorubicin and Rhodamine B through the formation of inclusion complexes with the β-CD component, but also the capability of targeted drug delivery to cancerous cells with a high level of expression of CD44 receptors, attributable to its HA component. The polymer can release the drug under slightly acidic conditions. With all its attributes, HA-β-CD may be a promising cancer-cell-targeting drug carrier.
研究领域:
药学
·
生物技术
·
纳米技术
·
药物递送系统
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2024
·
IF 5.5
Qingrong Li,Xiaoyuan Yang,Xuelin Xia,Xiao-Xia Xia,Deyue Yan
Recombinant elastin-like polypeptides (ELPs) have emerged as an attractive nanoplatform for drug delivery due to their tunable genetically encoded sequence, biocompatibility, and stimuli-responsive self-assembly behaviors. Here, we designed and biosynthesized an HER2 (human epidermal growth factor receptor 2)-targeted affibody–ELP fusion protein (Z-ELP), which was subsequently conjugated with monomethyl auristatin E (MMAE) to build a protein–drug conjugate (Z-ELP-M). Due to its thermal response, Z-ELP-M can immediately self-assemble into a nanomicelle at physiological temperature. Benefiting from its active targeting and nanomorphology, Z-ELP-M exhibits enhanced cellular internalization and deep tumor penetration in vitro. Moreover, Z-ELP-M shows excellent tumor targeting and superior antitumor efficacy in HER2-positive ovarian cancer, demonstrating a relative tumor growth inhibition of 104.6%. These findings suggest that an affibody-functionalized elastin-like peptide–drug conjugate nanomicelle is an efficient strategy to improve antitumor efficacy and biosafety in cancer therapy.
研究领域:
生物医学工程
·
肿瘤学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DALTON TRANSACTIONS
·
2013
·Vol. 42
·期 27
·9852-9861
·
IF 3.806
Yuan Wu,Dongmei Yang,Xiaojiao Kang,Ping'an Ma,Shanshan Huang,Yang Zhang,Chunxia Li,Jun Lin
Multifunctional nanocomposites integrating mesoporous and luminescence properties into a single entity are synthesized via a facile and effective approach. Oleic acid capped β-NaYF4:Ce3+/Tb3+ nanoparticles (NPs) are transferred into aqueous solution by cetyltrimethylammonium bromide (CTAB) surfactants, and further encapsulated with uniform mesoporous silica shell followed by the surface modification with poly(ethylene glycol) (PEG), leading to the formation of water-dispersible and biocompatible core–shell structured β-NaYF4:Ce3+/Tb3+@mSiO2-PEG (denoted as NPs@mSiO2-PEG) nanospheres. The as-synthesized nanospheres show a typical mesoporous structure and a green emission under UV irradiation. Doxorubicin hydrochloride (DOX), a widely used anti-cancer drug, is used as a model drug to evaluate the loading and controlled release behaviors of the NPs@mSiO2-PEG in phosphoric acidic buffer solutions (PBS) at different pH values (pH = 7.4 and 5.0). The composite carriers provide a pH-sensitive drug release pattern and the drug releases faster under lower pH value. The endocytosis process of fluorescein isothiocyanate (FITC)-labelled nanospheres is characterized using flow cytometry and confocal laser scanning microscopy (CLSM) against A549 cells. The in vitro cytotoxic effect against A549 cells of the DOX-loaded carriers is investigated in detail. In addition, the extent of drug release can be monitored by the variation of photoluminescence (PL) intensity of β-NaYF4:Ce3+/Tb3+. Considering the good biocompatibility and pH-dependent drug release pattern, such core–shell structured luminescent NPs@mSiO2-PEG nanospheres have potential applications in controlled drug delivery.
研究领域:
生物材料
·
纳米医学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
COLLOID AND POLYMER SCIENCE
·
2020
·Vol. 298
·期 8
·1119-1128
·
IF 1.536
Wang Qiang,Gao Feng,Zhou Xianyong
Compared with conventional drug nanocarriers, multifunctional drug delivery systems exhibited characteristic advantages. In this study, we developed a multifunctional drug delivery system possessing stimuli-responsive drug release and cellular imaging. Amphiphilic polymers, methoxypolyethylene glycol-cystamine-tetraphenylethene (mPEG 1k -SS-TPE), were synthesized by combining methoxypolyethylene glycol (mPEG 1k ) and tetraphenylethene (TPE) using reduction-sensitive disulfide bonds that can be disconnected by high level of inherent glutathione (GSH). Size distribution and morphology of mPEG 1k -SS-TPE micelles were evaluated. Meanwhile, the reduction-sensitivity of mPEG 1k -SS-TPE micelles was surveyed compared with that of mPEG 1k -TPE micelles. Nile Red was encapsulated into mPEG 1k -SS-TPE micelles to visually observe intracellular drug delivery against SW480 cells. Paclitaxel (PTX) was chosen to be loaded into micelles to evaluate the cytotoxicity against HCT116, HT-29, and SW480.
Graphical Abstract
研究领域:
生物材料
·
药物化学
·
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）