INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
·
IF 7.7
Yuqi Wu,Jiawei Li,Liang Liu,Xinhong Chu,Min Zhong,Hongkun Li,Chengcheng Zhao,Hui Fu,Yujiao Sun,Yingpeng Li
The oral delivery of doxorubicin (DOX), an anti-cancer drug, encounters multiple hurdles such as limited gastrointestinal permeability, P-glycoprotein-mediated efflux, brief intestinal residence, and rapid degradation. This study introduced a novel approach utilizing hyaluronic acid (HA)-grafted fatty acid monoglycerides (HGD) to encapsulate DOX, forming HGD-DOX nanoparticles, aimed at enhancing its oral bioavailability. Drug encapsulated by HGD provided several advantages, including extended drug retention in the gastrointestinal tract, controlled release kinetics, and promotion of lymphatic absorption in the intestine. Additionally, HGD-DOX nanoparticles could specifically target CD44 receptors, potentially increasing therapeutic efficacy. The uptake mechanism of HGD-DOX nanoparticles primarily involved clathrin-mediated, caveolin-mediated and macropinocytosis endocytosis. Pharmacokinetic analysis further revealed that HGD significantly prolonged the in vivo residence time of DOX. In vivo imaging and pharmacodynamic studies indicated that HGD possessed tumor-targeting capabilities and exhibited a significant inhibitory effect on tumor growth, while maintaining an acceptable safety profile. Collectively, these findings position HGD-DOX nanoparticles as a promising strategy to boost the oral bioavailability of DOX, offering a potential avenue for improved cancer treatment.
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Journal of Nanomaterials
·
2018
·
IF 2.207
Kun Wang,Shouju Wang,Kun Chen,Yijing Zhao,Xingqun Ma,Lin Wang
Anaplastic thyroid cancer (ATC) is highly aggressive and tends to develop drug resistance to standard chemotherapies. To overcome the drug resistance of ATC, we synthesized dopamine-melanin nanoparticles (MNPs) loaded with doxorubicin (Dox) molecules. The Dox-loaded MNPs (Dox-MNPs) developed exhibited increased cellular uptake and enhanced therapeutic efficacy in drug-resistant ATC cell line HTh74R, compared with free Dox. The native MNPs were found to have excellent biocompatibility, which suggests that Dox-MNPs may have potential in the treatment of ATC.
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SUPRAMOLECULAR CHEMISTRY
·
2024
·
IF 2.1
Caixia Li,Qin Zhou,Haoliang Huang,Liang Li
In this paper, Biocompatible supramolecular hydrogels, composed of β-cyclodextrin-modified hyaluronic acid, pluronic F127, α-cyclodextrin and doxorubicin, were constructed, which can be employed for targeted delivery system. The chemical composition and rheological properties of the obtained hydrogels were fully characterised. Considering the controlled complexation between DOX and the hydrogel skeletons, the controlled release of hydrogel G[5, 10, 5] was investigated to exhibit a better pH- and temperature-controlled release behavior. The data of DOX release kinetic was fitted well with Higuchi and Korsmeyer-Peppas models. Moreover, the cellular toxicity experiments indicated that the hydrogel DOX@G[5, 10, 5] exhibited a similar anticancer ability in comparison with free DOX. Due to the hyaluronic acid-targeted effects, the cytotoxicity of the hydrogel DOX@G[5,10,5] to HepG2 cells was lower than that to SKOV-3 cells upon increasing the concentration. Therefore, these hydrogels may act as a potential prospect for the targeting release of anticancer drugs.
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MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Wei Lin,Anyin Li,Lin Qiu,Hai Huang,Pengfei Cui,Jianhao Wang
One of the most significant reasons hindering the clinical translation of nanomedicines is the rapid clearance of intravenously injected nanoparticles by the mononuclear phagocyte system, particularly by Kupffer cells in the liver, leading to an inefficient delivery of nanomedicines for tumor treatment. The threshold theory suggests that the liver’s capacity to clear nanoparticles is limited, and a single high dose of nanoparticles can reduce the hepatic clearance efficiency, allowing more nanomedicines to reach tumor tissues and enhance therapeutic efficacy. Building upon this theory, researchers have conducted numerous validation studies based on the same nanoparticle carrier systems. These studies involve the use of albumin nanoparticles to improve the therapeutic efficacy of albumin nanomedicines as well as polyethylene glycol (PEG)-modified liposomal nanoparticles to enhance the efficacy of PEGylated liposomal nanomedicines. However, there is no research indicating the feasibility of the threshold theory when blank nanoparticles and nanomedicine belong to different nanoparticle carrier systems currently. In this study, we prepared two different sizes of albumin nanoparticles by using bovine serum albumin. We used the marketed nanomedicine liposomal doxorubicin hydrochloride injection (trade name: LIBOD, manufacturer: Shanghai Fudan-zhangjiang Biopharmaceutical Co., Ltd.), as the representative nanomedicine. Through in vivo experiments, we found that using threshold doses of albumin nanoparticles still can reduce the clearance rate of LIBOD, prolong its time in vivo, increase the area under the plasma concentration–time curve (AUC), and also lead to an increased accumulation of the drug at the tumor site. Furthermore, evaluation of in vivo efficacy and safety further indicates that threshold doses of 100 nm albumin nanoparticles can enhance the antitumor effect of LIBOD without causing harm to the animals. During the study, we found that the particle size of albumin nanoparticles influenced the in vivo distribution of the nanomedicine at the same threshold dose. Compared with 200 nm albumin nanoparticles, 100 nm albumin nanoparticles more effectively reduce the clearance efficiency of LIBOD and enhance nanomedicine accumulation at the tumor site, warranting further investigation. This study utilized albumin nanoparticles to reduce hepatic clearance efficiency and enhance the delivery efficiency of nonalbumin nanocarrier liposomal nanomedicine, providing a new avenue to improve the efficacy and clinical translation of nanomedicines with different carrier systems.
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JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY
·
2017
·Vol. 17
·期 5
·2873-2880
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IF 1.483
Huang Saiyan,Liu Jieying,Zhu Hao,Hussain Abid,Liu Qing,Li Jing,Shen Yuanyuan,Cheng Jiejun,Guo Shengrong
A novel folate-polyethylene glycol-succinic acid-doxorubicin conjugate (FA-PEG-SA-DOX) micelle loaded with curcumin (CUR) is designed and prepared to target tumor cells via folate-folate receptor interactions and co-deliver chemotherapeutic agent DOX and chemosensitizer CUR for treatment
of multidrug resistant human breast cancer MCF-7/ADR cells. The CUR/FA-PEG-SA-DOX micelles are characterized with the average size of 90.64±0.15 nm and the zeta potential of −15.3±0.8 mV. The CUR and DOX contents of the micelles are 12.07 and 15.69% (w/w), respectively.
The cytotoxicity, cellular uptake and effiux of the micelles are investigated by using MCF-7/ADR cells. The results demonstrate that the CUR/FA-PEG-SA-DOX micelles have greater toxicity (IC50 = 3.10 µg/ml) compared to the free DOX (IC50 = 31.99 µg/ml),
moreover, the micelles present increased cellular uptake and reduced cellular effiux. The combination index of CUR/FA-PEG-SA-DOX micelles was 0.17, which indicate a strong synergistic antitumor efficacy against MCF-7/ADR cells. These results suggest that Curcumin-loaded FA-PEG-SA-DOX micelles
may be a promising nanomedicine for co-delivery dual-drug treatment for cancer.
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EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
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2017
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IF 4.159
Qian Xie,Wenji Deng,Xue Yuan,Huan Wang,Zhiguo Ma,Baojian Wu,Xingwang Zhang
Liposomes have shown to be an excellent drug delivery system , but the short in vivo fate discourages their popularity. This work aimed to develop selenium-functionalized liposomes (SeLPs) for doxorubicin (Dox) delivery to prolong the systemic circulation of liposomes by in situ selenium coating and enhance the anticancer effect via the synergy between Dox and selenium. Dox-loaded SeLPs (Dox-SeLPs) were prepared by film hydration/active loading/ in situ reduction technique and characterized by particle size, entrapment efficiency and morphology. The resulting Dox-SeLPs were 127 nm around in particle size (uncoated liposomes 107 nm) and were spherical in morphology. It was shown that Dox-SeLPs possessed a sustained release effect for Dox and could increase the cellular uptake of Dox compared with Dox-loaded liposomes (Dox-LPs). The accumulative Dox release from Dox-SeLPs was 46.5% and it was 64.9% for Dox-LPs within 84 h. Moreover, Dox-SeLPs exhibited slower drug release in the fetal bovine serum. Trafficking pathway study revealed that clathrin-mediated endocytosis and macropinocytosis were involved in the cellular uptake process of Dox-SeLPs. The in vitro cytotoxicity and apoptosis test indicated that Dox-SeLPs had higher cytotoxicity than that of free Dox and Dox-LPs. Dox-SeLPs showed a IC 50 of 0.92 ± 0.16 μg/mL on A549 cells, far lower than that of free Dox (4.40 ± 0.58 μg/mL) and Dox-LPs (5.68 ± 0.73 μg/mL). Dox-SeLPs significantly improved the pharmacokinetic property and enhanced the antitumor efficacy of Dox in tumor-bearing mice. In conclusion, SeLPs exhibit good sustained release for Dox and have synergic anticancer effect with Dox, which may be promising as drug delivery vehicle .
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Polymer Chemistry
·
2017
·Vol. 8
·期 10
·1680-1688
·
IF 5.375
Jian Sheng,Ying Wang,Lu Xiong,Qiaojie Luo,Xiaodong Li,Zhiquan Shen,Weipu Zhu
Dendron-like multifunctional β-cyclodextrin–poly(ethylene glycol) (CD–PEG) conjugates were synthesized from amino functionalized β-cyclodextrins and poly(ethylene glycol) diacrylate through the Michael addition reaction. The resultant conjugates contain several PEG arms terminated with acrylates, which originated from the same glucopyranose unit of CD. These dendron-like CD–PEG conjugates can incorporate adamantane-modified doxorubicin (AD–DOX) by host–guest interactions between CD and AD moieties, to give a reactive supramolecular polymeric prodrug, which can be further crosslinked by poly[oligo(ethylene glycol) mercaptosuccinate] (POEGMS) via thiol–ene “click” reaction under physiological conditions. These kinds of in situ forming drug-loaded hydrogels can be utilized as injectable gelling carriers for localized drug delivery.
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MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Tingjun Dong,Ning Yang,Jian Qin,Chengcheng Zhao,Tingyu Gao,Hao Ma,Caili Zhu,Huan Xu
Renal fibrosis plays a key role in the pathogenesis of chronic kidney disease (CKD), in which the persistent high expression of transforming growth factor β1 (TGF-β1) and α-smooth muscle actin (α-SMA) contributes to the progression of CKD to renal failure. In order to improve the solubility, bioavailability, and targeting of tanshinone IIA (Tan IIA), a novel targeting material, aminoethyl anisamide-polyethylene glycol-1,2-distearoyl-sn-glycero-3-phosphate ethanolamine (AEAA-PEG-DSPE, APD) modified Tan IIA liposomes (APD-Tan IIA-L) was constructed. An animal model of glomerulonephritis induced by doxorubicin in BALB/c mice was established. APD-Tan IIA-L significantly decreased blood urea nitrogen and serum creatinine (SCr), and the consequences of renal tissue oxidative stress indicators showed that APD-Tan IIA-L downregulated malondialdehyde, upregulated superoxide dismutase, catalase, and glutathione peroxidase. Masson’s trichrome staining showed that the deposition of collagen in the APD-Tan IIA-L group decreased significantly. The pro-fibrotic factors (fibronectin, collagen I, TGF-β1, and α-SMA) and epithelial–mesenchymal transition marker (N-cadherin) were significantly inhibited by APD-Tan IIA-L. By improving the microenvironment of fibrotic kidneys, APD-Tan IIA-L attenuated TGF-β1-induced excessive proliferation of fibroblasts and alleviated oxidative stress damage to the kidney, providing a new strategy for the clinical treatment of renal fibrosis.
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Nanomaterials
·
2024
·Vol. 14
·期 10
·864
·
IF 4.4
Xiao-Min Cao,Yuan-Qiu Cheng,Meng-Meng Chen,Shun-Yu Yao,An-Kang Ying,Xiu-Zhen Wang,Dong-Sheng Guo,Yue Li
Chemotherapy is one of the most commonly used methods for treating cancer, but its side effects severely limit its application and impair treatment effectiveness. Removing off-target chemotherapy drugs from the serum promptly through adsorption is the most direct approach to minimize their side effects. In this study, we synthesized a series of adsorption materials to remove the chemotherapy drug doxorubicin by modifying MOF nanosheets with sulfonated azocalix[4]arenes. The strong affinity of sulfonated azocalix[4]arenes for doxorubicin results in high adsorption strength (Langmuir adsorption constant = 2.45–5.73 L mg−1) and more complete removal of the drug. The extensive external surface area of the 2D nanosheets facilitates the exposure of a large number of accessible adsorption sites, which capture DOX molecules without internal diffusion, leading to a high adsorption rate (pseudo-second-order rate constant = 0.0058–0.0065 g mg−1min−1). These adsorbents perform effectively in physiological environments and exhibit low cytotoxicity and good hemocompatibility. These features make them suitable for removing doxorubicin from serum during “drug capture” procedures. The optimal adsorbent can remove 91% of the clinical concentration of doxorubicin within 5 min.
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JOURNAL OF SEPARATION SCIENCE
·
2025
·Vol. 48
·期 8
·e70249
·
IF 2.8
Tian Yawen,Jiang Xinhui,Wang Jie,Cui Jiaping,Fu Xinru,Xia Zhining,Huang Yike
In this study, dual stimulus-response molecularly imprinted hydrogels (MIHs) with water-soluble doxorubicin (DOX) as the imprinted molecule were developed for improving the selective specific recognition capacity. By using N-isopropylacrylamide (NIPAM) as a temperature-sensitive monomer, and N-[3-(dimethylamino)propyl]methacrylamide (DMAPMA) as a pH-responsive functional monomer, a series of MIHs with different concentration ratios of dual functional monomers and cross-linker were prepared to study the influencing factors of selective recognition. The results show the prepared MIHs have different rigidity and flexibility under different synthesis conditions. The MIH7 with good adsorption performance and specific recognition ability was selected with its molar ratio of NIPAM/DMAPMA/cross-linker (200/10/100). Its imprinting factor of DOX was as high as 2.26. Adsorption kinetic and adsorption thermodynamic studies showed that MIH7 and DOX had high affinity, and its affinity constant K D was as high as 9.11 × 10 −6 mol/L. For selectivity adsorption, the MIH7 had excellent selectivity at pH 5, with a selectivity factor as high as 1.97 for epirubicin, which is extremely similar in structure, and selectivity factors as high as 6 and 7.68 for idarubicin and oxytetracycline, respectively. The prepared MIH7 was well separated with good specific recognition of DOX in the serum samples, which provided a potential strategy based on the dual stimulus-response and cross-linker for the efficient recognition of water-soluble molecules.
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ACS Omega
·
2025
·
IF 4.3
Na Feng,Junjie Chang,Honglei Yu,Tongfei Li,Lin Lei,Xiaomin Huang,Dandan Shi,Rui Liu,Wenjun Zhang,Xiju He
Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related death worldwide. Doxorubicin (Dox), a conventional chemotherapeutic agent, exhibits unsatisfactory efficacy in HCC due to its poor tumor response, severe cardiotoxicity, and drug resistance. It is urgent to develop strategies to mitigate the side effects and enhance the chemosensitivity of conventional chemotherapy drugs. Traditional Chinese medicine has gained research interest in cancer treatment due to its homology with food and minimal side effects. Puerarin (Pue) has been identified as an effective inhibitor of tumor cell proliferation. However, puerarin’s poor water solubility and bioavailability limit its pharmaceutical application. In this study, a novel puerarin nanoparticle (nanoPue) was developed to overcome its limitation. NanoPue could significantly inhibit tumor growth and enhance the chemotherapeutic effect of Dox in HCC models. NanoPue could increase the perivascular coverage within the tumors; decrease the expressions of NSUN2, p-AKT, VEGFA, and MMP-9; and reduce endothelial cell tube formation. In summary, nanoPue improves Dox therapeutic efficacy by decreasing angiogenic factors via regulating NSUN2 in HCC. This study may provide a potential avenue for advancing nanoPue to enhance chemotherapeutic agents in HCC therapy and supply a theoretical support for the clinical application of nanoPue.
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INORGANIC CHEMISTRY COMMUNICATIONS
·
2025
·
IF 5.4
Peijian Yang,Ying Li,Haiyun Zhai,Xiulan Cai
The aim of this study is to develop a novel molybdenum oxide nanocomposite with good dispersion and targeting tumor cells and investigate their DOX delivery performance. Briefly, molybdenum oxide (MoO x ) nanocomposite prepared by hydrothermal method were grafted with polyglycerol (MoO x -PG), followed by stepwise organic coupling with RGD peptide (MoO x -PG-RGD), and finally loaded with DOX. The physicochemical properties of MoO x -PG-RGD nanocomplexes were characterized by FTIR, SEM, XPS and TGA. The results showed that the grafted PG layer largely enhanced the dispersibility and biocompatibility of MoO x nanocomposite in physiological media. The obtained MoO x -PG-RGD/DOX exhibited drug-loading efficiency of 18.67 %. Drug release experiments indicated that MoO x -PG-RGD/DOX exhibited a faster release rate under acidic conditions in tumors. In addition, MTT cytotoxicity assay and cell uptake experiments indicated that MoO x -PG-RGD/DOX efficiently delivered DOX into targeted cells by integrin α v β 3 receptor-mediated endocytosis, which leading to an enhanced therapeutic efficacy of DOX. These results suggested that MoO x -PG-RGD, as a novel anticancer drug delivery vector, had great potential for application in tumor therapy.
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