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.
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高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Binke Wang,Xinyu Qi,Ruping Yang,Xu Xu,Shiyao Li,Chunli Zhang,Haitao Yu
Liver cancer is one of the most prevalent and deadly malignancies worldwide, with limited effective therapeutic strategies. Although doxorubicin (DOX) is widely used as a frontline chemotherapeutic agent, its severe cardiotoxicity and lack of tumor selectivity significantly limited its clinical applications. Polydatin (PLD), a natural antioxidant and anticancer compound, has shown promise as an adjuvant for reducing DOX-induced cardiotoxicity, yet its poor bioavailability hinders its therapeutic potential. To improve the therapeutic efficacy of DOX while reducing systemic toxicity, we developed a hyaluronic acid (HA)-functionalized cubosome-based nanosystem co-loaded with DOX and PLD (1:3 ratio), i.e. HA 3% -D/P-CUBS + , to specifically target tumor sites with enhanced antitumor efficiency and alleviated DOX-induced cardiotoxicity. HA 3% -D/P-CUBS + significantly improved drug internalization and induced apoptosis in hepatocellular carcinoma cells (HepG-2 and HUH-7). Meanwhile, HA 3% -D/P-CUBS + protected normal hepatocytes (HL-7702 and AML-12) and reduced oxidative stress in cardiomyocytes (H9C2 cells). Notably, HA 3% -D/P-CUBS + inhibited in vivo tumor growth of 94 % without causing damage to vital organs, leading to improved survival rates. Moreover, it also mitigated DOX-induced oxidative stress by restoring the balance between oxidative and antioxidant systems. These findings highlight HA 3% -D/P-CUBS + as a promising and synergistic nanomedicine for targeted live cancer therapy, providing new insights into combination chemotherapy with enhanced safety and efficacy.
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ACS Biomaterials Science & Engineering
·
2025
·
IF 5.5
Tianhui Liu,Qingshuang Wang,Wenxin Geng,Xue Jiang,Changshun Lu,Zhe Zhang,Xiangru Feng
The cancer-associated fibroblasts (CAFs) in tumor stroma present substantial barriers to drug penetration, resulting in tumor resistance and progression. One promising strategy is to reprogram CAFs into a quiescent state, which necessitates novel approaches. Our study introduces a sequential treatment strategy using chitosan thermosensitive hydrogels loaded with α-Mangostin (α-M), a small molecule drug with antifibrotic properties, aimed at reprogramming CAFs within the breast cancer tumor microenvironment (TME). We developed glutathione (GSH)-responsive nanoparticles (NPc) that carry the chemotherapeutic drug doxorubicin (DOX). Treatment with α-M results in the downregulation of CAF-specific biomarkers and a remodeled TME, which improves the penetration of NPc/DOX deep into the tumor tissue. This strategy holds great promise in enhancing cancer therapeutic outcomes in tumors rich in CAFs, particularly in the case of breast cancer.
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PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2016
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IF 2.326
Zhenhua Fang,Yanpeng Sun,Hong Xiao,Peng Li,Ming Liu,Fan Ding,Wusheng Kan,Runsheng Miao
Osteosarcoma is the most common primary malignant bone tumor in the pediatric age group, and chemotherapy directed by targeted nanoparticulate drug delivery system represents a promising approach for osteosarcoma treatment recently. Here, we designed and developed a novel DOX-loaded targeted polymeric micelle self-assembled from RGD-terminated poly(ethylene glycol)- block -poly (trimethylene carbonate) (RGD-PEG-PTMC) amphiphilic biodegradable block copolymer , for high-efficiency targeted chemotherapy of osteosarcoma. Notably, the RGD-installed DOX-loaded biodegradable polymeric micelle (RGD-DOX-PM) with drug loading efficiency of 57%–73% displayed a narrow distribution (PDI = 0.05–0.12) with average sizes ranging from 46 to 73 nm depending on the DOX loading content. The release amount of DOX from RGD-DOX-PM achieved 63% within 60 h under physiological condition. Interestingly, MTT assays in MG-63 and MNNG/HOS osteosarcoma cells exhibited that half-maximal inhibitory concentration (IC 50 ) value of RGD-DOX-PM was much lower than its non-targeted counterpart (DOX-PM), implying RGD decorated nanoparticles had enhanced cell targeting ability and led to more effective anti-tumor effect. Furthermore, the targeting ability of RGD-DOX-PM was confirmed by in vitro flow cytometry and confocal laser scanning microscopy (CLSM) imaging assays, where the results showed more RGD-DOX-PM were taken up by MG-63 cells than that of DOX-PM. Therefore, this RGD decorated DOX-loaded polymeric micelle is promising for targeted chemotherapy of osteosarcoma.
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高影响因子
BIOMATERIALS
·
2020
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IF 10.317
Tong Chen,Tongxu Gu,Liang Cheng,Xiang Li,Gaorong Han,Zhuang Liu
Overexpression of P-glycoprotein (P-gp), which is responsible for pumping chemotherapeutic drugs out of tumor cells, has been recognized as an important cause of drug resistance in conventional chemotherapy. Herein, porous platinum nanoparticles (pPt NPs) are developed to enable the combined electrodynamic therapy (EDT) with chemotherapy. With polyethylene glycol (PEG) coating, the obtained pPt-PEG NPs could be loaded with anticancer drug doxorubicin (DOX) by utilizing the porous structure of pPt NPs. Those pPt-PEG NPs are able to produce reactive oxygen species (ROS) by triggering water decomposition under electric field, independent of O 2 and H 2 O 2 contents in the tumor. Furthermore, the ROS generated during EDT could induce the inhibition of P-glycoprotein (P-gp), in turn enhancing the efficacy of chemotherapeutic agents by facilitating intracellular accumulation of drugs. As the results, excellent synergetic therapeutic effects were observed by combining chemotherapy with EDT using DOX-loaded pPt ( [email protected] ) NPs, as demonstrated by both in vitro and in vivo experiments. This study demonstrates a new concept of combinational cancer therapy with superior therapeutic efficacy.
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高影响因子
ACS Applied Bio Materials
·
2021
·
IF 0
Lihong Li,Qi Zhang,Jinyao Li,Yafei Tian,Yu Kang,Guodong Ren,Wen Liu,Haojiang Wang,Bin Wang,Lili Yan,Lixia Guo,Haipeng Diao
A transferrin receptor (TfR)-targeted nanodrug [green fluorescence emission carbon dot (GCD)–polyethylene glycol (PEG)–transferrin (Tf)@doxorubicin (Dox)] for cancer therapy was developed by functionalizing GCDs with PEG, Tf, and Dox. GCDs were synthesized by the one-step hydrothermal method, followed by conjugating PEG and Tf by covalent bonds and loading Dox by electrostatic interactions. The nanodrug exhibits high stability under neutral conditions and effectively releases Dox at pH of 5.5. GCD–PEG–Tf@Dox can be selectively internalized by TfR-overexpressed tumor cells (MCF-7 and K150) via receptor-mediated endocytosis and further release Dox to the nuclei. As a result, GCD–PEG–Tf@Dox exhibits significant lethality to tumor cells (MCF-7 and K150) but greatly reduced toxicity to normal cells [Chinese hamster ovary cell line (CHO)] compared with free Dox. In vivo studies have confirmed that GCD–PEG–Tf@Dox can effectively inhibit tumor proliferation with negligible side effects.
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PubMed
Frontiers in Pharmacology
·
2019
·
IF 3.845
Li Ke,Zhan Wenhua,Chen Yulong,Jha Rajiv Kumar,Chen Xueli
Combination chemotherapy has been proven to be an efficient strategy for the treatment of prostate cancer (PCA). However, the pharmacokinetic distinction between the relevant drugs is an insurmountable barrier to the realization of their synergistic use against cancer. To overcome the disadvantages of combination chemotherapy in the treatment of PCA, targeted nanoparticles (NPs), which can codeliver docetaxel (DOC) and doxorubicin (DOX) at optimal synergistic proportions, have been designed. In this study, the DOC and DOX codelivery nanoparticles (DDC NPs) were constructed by hyaluronic acid (HA) and cationic amphipathic starch (CSaSt) through a self-assembly process. Human PCA cell lines (PC-3, DU-145, and LNCap) and mouse models were then used for evaluation in vitro and in vivo, respectively, of delivery and antitumor effects. The DDC NPs were spherical with rough surfaces, and the size and zeta potential were 68.4 ± 7.1 nm and -22.8 ± 2.2 mV, respectively. The encapsulation efficiencies of DOC and DOX in the NPs were 96.1 ± 2.3% and 91.4 ± 3.7%, respectively, while the total drug loading was 9.1 ± 1.7%. Moreover, the ratio of DOC to DOX in the DDC NPs was approximately 1:400, which aligned with the optimal synergistic proportions of the drugs. The DDC NPs exhibited excellent loading capacities, performed sustained and enzymatic release, and were stable in PBS, medium, and serum. After investigations in vitro, the DDC NPs were as effective as the dual drug combination in terms of cytotoxicity, antimigration, and apoptosis. Internalization results indicated that the DDC NPs could effectively deliver and fully release the payloads into PCA cells, and the process was mediated by the ligand-receptor interaction of HA with the CD44 protein. Low toxicity in vivo was confirmed by acute toxicity and hemolytic assays. The distribution in vivo showed that DDC NPs could enhance the accumulation of drugs in tumors and decrease nonspecific accumulation in normal organs. More importantly, DDC NPs significantly promoted the curative effect of the DOC and DOX combination in the PCA cell xenograft mouse model, indicating that the drugs with NPs did indeed act synergistically. This study suggests that the DDC NPs possess noteworthy potential as prospects for the development of PCA clinical chemotherapy.
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PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2022
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IF 3.841
Guo Yi,Junhong Ling,Yongjun Jiang,YuQing Lu,Li-Ye Yang,Xiao–kun Ouyang
In this study, we developed pH-sensitive chito-oligosaccharide nano-drug-loaded particles with good biocompatibility, biodegradation, and controlled drug delivery. Chitosan oligosaccharides (COS), Doxorubicin (DOX) amino groups, and aromatic aldehydes of benzaldehyde-terminated polyethylene glycol were used to spontaneously form pH-sensitive aniline bonds. We aimed to achieve site targeting under weak acidic tumor conditions, improve the efficacy, and reduce the toxic side effects of the drug. Particle size, drug encapsulation efficiency, loading efficiency, and zeta potential of nanoparticles were optimized by altering the ratios of aldehyde, amino groups, and sodium tripolyphosphate. The drug encapsulation efficiency and loading efficiency of COS-DOX1 were 5.55 ± 0.13% and 88.81 ± 2.00%, respectively, and the in vitro drug release process displayed a specific pH responsiveness. Co-culture of COS-DOX with HCT-116 human colon cancer cells showed that the nanoparticles exhibited dose-dependent cytotoxicity. At a low dose, COS-DOX1 can promote DOX uptake of tumor cells and exhibit higher cytotoxicity than DOX alone.
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Journal of Nano Research
·
2017
·
IF 0.511
Cao Ming,Xiao Wan Song,Yu Jiao Zhang,Chang Zhi Xu,Peng Chen,Ru Xia,Tian Long Hu,Jia Sheng Qian,Ke Liang Wu
pH responsive polymeric nanoparticles have emerged as a promising technology platform for targeted and controlled drug delivery in recent years. In this paper, endosomal pH-activatable doxorubicin (DOX) and core-crosslinked polymeric nanoparticles (DCNPs) were prepared and investigated for potent growth inhibition of human cancer cells in vitro. In vitro drug release studies, DOX conjugated nanoparticles with hydrazone bond showed a pH sensitive release phenomenon, that is, the releasing is significantly faster at mildly acidic condition with pH of 5.5 than that at physiological condition. Confocal laser scanning microscope (CLSM) observations revealed that DOX conjugated nanoparticles delivered and released DOX into the cytosols as well as cell nuclei of Hela cells following 6 h incubation. MTT assays demonstrated that these pH-sensitive DOX nanoparticles exhibited high antitumor effect to HeLa cells. The conjugated DOX polymeric nanoparticles may be a promising candidate as a nanoscale and pH-sensitive drug delivery vehicle for cancer therapy.
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ADVANCES IN POLYMER TECHNOLOGY
·
2025
·Vol. 2025
·期 1
·9396134
·
IF 2.5
Ye Fan,Ming Lu,Junyi Huang,Ling Huang,Huade Zheng
Drug-eluting embolic microspheres are receiving increasing attention in transarterial chemoembolization (TACE), which is one of the most important approaches for the treatment of unresectable hepatocellular carcinoma (HCC). However, currently most commercial microspheres are radiolucent and their position in vivo needs to be indirectly monitored by X-ray angiography. In addition, microspheres reflux may cause nontargeted embolism. The aim of this study is to develop an inherently radiopaque embolic agent capable of delivering drugs and enhancing the embolic effect. In this study, using emulsification (S/W/O) and photocrosslinking, the mixture of methacrylated polyvinyl alcohol (PVAMA), 2-acrylamide-2-methylpropanesulfonic acid (AMPS), and barium sulfate was prepared into BaSO 4 /PVA/AMPS beads. Barium sulfate act as computed tomography (CT) contrast agent, while sulfonic acid groups give the hydrogel beads drug loading and sustained release properties. The embolic performance of beads is enhanced by loading etamsylate. The results indicate that the prepared beads are radiopaque, biocompatible, with good drug sustained release performance. In vivo embolization and imaging properties were demonstrated by a rabbit ear central artery embolization model.
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COLLOIDS AND SURFACES B-BIOINTERFACES
·
2022
·
IF 5.999
Xiao Ma,Caihong Yang,Ruirui Zhang,Jie Yang,Yan Zu,Xin Shou,Yongxiang Zhao
Doxorubicin (DOX) is a powerful chemotherapy drug for cancer treatment, especially in patients with advanced cancer. However, clinical use of DOX remains challenging due to its widespread drug resistance and severe cardiotoxicity. Here, we developed a novel DOX-loaded natural hydrogel microparticle by using microfluidic electrospray technology. The designed carboxymethyl cellulose-based hydrogel microparticles were cross-linked by iron ions and showed a sustained drug release . The animal experiments revealed that DOX-loaded microparticles had good biocompatibility when locally injected into tumor-bearing mice, and could enhance the effect of chemotherapy and effectively inhibit tumor growth without obvious toxicity. These features indicated that the natural biomass-based hydrogel microparticles are highly promising for chemotherapy drugs delivery and provide a platform for local therapy.
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高影响因子
Drug Delivery and Translational Research
·
2024
·Vol. 14
·期 11
·3163-3172
·
IF 5.7
Wang Lijie,Yu Dahai,Li Dan,Li Jing
The impact of optically active biomaterials on drug delivery remains a vital and hot topic. To reveal special advantages of optically active mesoporous silica nanoparticles in delivering drug in cells, optically active mesoporous silica nanoparticles deliver doxorubicin (DOX) with chiral behavior in cancer cells was studied. The present work focused on two types of optically active mesoporous silica nanoparticles named as levorotatory optically active mesoporous silica nanoparticles (LOA-MSNs) and dextrorotatory optically active mesoporous silica nanoparticles (DOA-MSNs) and examined their effects on cellular DOX delivery in cancer cells. The obtained LOA-MSNs and DOA-MSNs were regular spheres with particle diameters ranging from 200 to 250 nm, and their shell layer was filled with interlaced channels. Our results indicated that LOA-MSNs and DOA-MSNs did not exhibit cytotoxicity towards MCF-7 cells and B16 cells. The cytotoxicity of DOX-loaded LOA-MSNs and DOX-loaded DOA-MSNs were stronger than DOX owing to the synergistic retention and accumulation effect of nanoparticles. More importantly, DOX-loaded DOA-MSNs presented stronger cytotoxicity due to the higher synergistic retention and accumulation effect of DOA-MSNs. These findings suggest that DOA-MSNs with superior cellular delivery of DOX have great potential to advance the development of optical anti-tumor delivery system. Graphical abstract
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危险品化学品经营许可证（带存储）