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Doxorubicin
ACS Applied Nano Materials · 2021 · IF 5.097

11-Mercaptoundecanoic Acid-Functionalized Carbon Dots As a Ratiometric Optical Probe for Doxorubicin Detection

Li Zhang,Huaizhong Xing,Wei Liu,Zihan Wang,Yumin Hao,Huiping Wang,Wenjuan Dong,Yang Liu,Shaomin Shuang,Chuan Dong,Xiaojuan Gong

A ratiometric optical dual-mode probe was first designed for the detection of doxorubicin (DOX) based on 11-mercaptoundecanoic acid-functionalized carbon dots (MUA-CDs). The carbon dots (CDs) were synthesized via hydrothermal carbonization of m-phenylenediamine and p-aminobenzoic acid, and then it was reacted with 11-mercaptoundecanoic acid by the amide reaction to obtain the MUA-CDs. The as-synthesized MUA-CDs have a high fluorescence quantum yield (59.4%) with bright green emission. Based on a specific electrostatic interaction and the fluorescence resonance energy transfer (FRET) between MUA-CDs and DOX, a ratiometric optical dual-mode probe was constructed for the detection of DOX with good selectivity, high sensitivity, and excellent anti-interference performance. When DOX was mixed the MUA-CDs, the fluorescence of the MUA-CDs at 513 nm decreased, while the fluorescence at 590 nm increased. With this information, a ratiometric fluorescent method was established to determine DOX with a linear range and limit of detection (LOD) of 0.25–19.96 and 0.66 μM and 50.33–80.88 and 0.23 μM, respectively. Meanwhile, the color of the MUA-CDs varied from colorless to dark yellow in the presence of DOX, and therefore, a ratiometric colorimetric method was applied to determine DOX in a range of 2.50–29.80 μM with a LOD of 0.75 μM. Finally, the as-constructed probe was successfully used to determine DOX in serum, urine, and live cells with satisfactory results. This work will contribute to the specific design of functional CDs and broaden the application of functional CDs in analytical detection and biological imaging.

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COLLOIDS AND SURFACES B-BIOINTERFACES · 2023 · IF 5.8

Pectin based hydrogel with covalent coupled doxorubicin and limonin loading for lung tumor therapy

Danyang Chen,Xiangbo Ma,Jingjing Zhu,Yong Wang,Shuai Guo,Jianglei Qin

Self-healing hydrogels have shown great application potential in drug delivery for anti-tumor therapy and tissue engineering. In this research, Doxorubicin (DOX) was coupled onto the oxidized pectin (pec-Ald) to prepare DOX grafted pec-AD and used to fabricate self-healing hydrogel for lung cancer therapy combined with novel herbal medicine extract limonin targeting lung cancer cells. The hydrogel was prepared with P(NIPAM 195 - co -AH 54 ) cross-linking and the hydrazone bond cross-linked hydrogel showed good mechanical property and self-healing behavior. With pectin composition , the hydrogel was still biodegradable catalyzed by enzyme and in vivo. The hydrogel formed fast fit for injectable application and the hydrogel itself showed moderate lung cancer inhibition activity. With limonin loading, the hydrogel showed synergistic lung cancer therapy with the tumor growth greatly inhibited. The covalent coupling of DOX and loaded limonin in the hydrogel decreased in vivo toxicity and the hydrogel degraded on time. With biodegradability and improved lung cancer therapy efficiency, this DOX grafted self-healing hydrogel could find great potential application in cancer therapy in near future.

CAS / MDL: 7790-28-5
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AIP Advances · 2023 ·Vol. 13 ·期 11 · IF 1.6

Polypyrrole nanoparticles loaded with doxorubicin for pH-responsive combinational photothermal-chemotherapy of cancer cells

Liu Jinhua,Zhu Guoren,Liu Yuanan,Wang Xiaohui

The combined treatment method integrated photothermal therapy (PTT) with chemotherapy is extremely promising owing to the synergistic therapeutic effect as compared to single PTT or chemotherapy. To facilitate more novel and facile photothermal-chemotherapy drugs as well as promote controllable combination therapy, we have developed a mild and facile method to fabricate polymer polypyrrole (PPy)-doxorubicin (DOX) nanoparticles (NPs) as pH-responsive drug nanocarriers for synergistic photothermal-chemotherapy. In the nanoplatform, poly-L-lysine (PLL)-modified PPy serves as the photothermal material, and (DOX) molecules are adopted as the chemotherapy agent. Based on the cross-linking reaction of glutaraldehyde, DOX molecules are flexibly and efficiently assembled on the surface of PLL-modified PPy NPs. The obtained PPy-DOX NPs possess high photothermal effect, superior loading capacity of DOX, and controlled drug release behavior. The combination photothermal-chemotherapy based on PPy-DOX NPs has significantly enhanced the antitumor therapy effect. In general, the designed PPy-DOX NPs may be a potential drug delivery nanoplatform for cancer combination therapy.

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EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY · 2021 · IF 6.514

Doxorubicin-loaded natural daptomycin micelles with enhanced targeting and anti-tumor effect in vivo

Quanling Guo,Lu Zhang,Mengmeng He,Xiaohua Jiang,Jingrui Tian,Qiurong Li,Zhiwei Liu,Longgang Wang,Haotian Sun

Development of a simple method to enhance targeting and anti-tumor effect of the chemotherapeutic agents in vivo is a major problem. Amphipathic and natural daptomycin is biocompatible antibacterial polypeptide used in clinical practice. Herein, doxorubicin (DOX) was stabilized by zwitterionic daptomycin (Dap) micelles in aqueous solution to form a zwitterionic nanodrug (Dap-DOX micelles). The hydrodynamic size and zeta potential of Dap-DOX micelles were 85  nm and −10 mV, respectively. The study on the controlled release showed that more DOX molecules were released from Dap-DOX micelles at acidic condition of tumor tissue than that at neutral condition of normal tissue which was due to pH responsiveness of Dap-DOX micelles. Dap-DOX micelles exhibited good stability in fibrinogen solution. Moreover, MTT studies showed that Dap-DOX micelles had higher cytotoxicity than free DOX. Notably, the results of flow cytometry indicated that the average fluorescence intensity of Dap-DOX micelle-treated cells was higher than that of free DOX-treated cells, and acidic conditions were more favorable for Dap-DOX micelles than normal pH in cell uptake assay. More importantly, Dap-DOX micelles were biocompatible in vivo based on the changes of weight and blood indexes of mice. Dap-DOX micelles were selectively accumulated at tumor sites in vivo through EPR effect , which reduced the toxicity of free DOX and achieved excellent tumor inhibition effect. The tumor inhibition rate of Dap-DOX micelles reached 96%. Dap-DOX micelles also effectively inhibited the growth of bacterial. Taken together, Dap-based drug delivery systems are promising and effective in cancer therapy.

CAS / MDL: 25316-40-9 298-93-1
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DRUG DELIVERY · 2021 · IF 6.419

Self-assembled polymeric nanocarrier-mediated co-delivery of metformin and doxorubicin for melanoma therapy

Mingming Song,Wentao Xia,Zixuan Tao,Bin Zhu,Wenxiang Zhang,Chang Liu,Siyu Chen

Malignant melanoma is a life-threatening form of skin cancer with a low response rate to single-agent chemotherapy. Although combined therapies of metformin (MET) and doxorubicin (DOX) are effective in treating a variety of cancers, including breast cancer, their different physicochemical properties and administration routines reduce the effective co-accumulation of both drugs in tumors. Nanoparticles (NPs) have been demonstrated to potentially improve drug delivery efficiency in cancer therapy of, for example, liver and lung cancers. Hence, in this study, we prepared pH-sensitive, biocompatible, tumor-targeting NPs based on the conjugation of biomaterials, including sodium alginate, cholesterol, and folic acid (FCA). As expected, since cholesterol and folic acid are two essentials, but insufficient, substrates for melanoma growth, we observed that the FCA NPs specifically and highly effectively accumulated in xenograft melanoma tumors. Taking advantage of the FCA NP system, we successfully co-delivered a combination of MET and DOX into melanoma tumors to trigger pyroptosis, apoptosis, and necroptosis (PANoptosis) of the melanoma cells, thus blocking melanoma progression. Combined, the establishment of such an FCA NP system provides a promising vector for effective drug delivery into melanoma and increases the possibility and efficiency of drug combinations for cancer treatment.

CAS / MDL: 1154-25-2 69-09-0
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY · 2020 · IF 2.734

Self-assembly of pH-sensitive micelles for enhanced delivery of doxorubicin to melanoma cells

Miaomiao Long,Shenhuan Liu,Xiaotian Shan,Jing Mao,Fuwei Yang,Xiaoyu Wu,Lipeng Qiu,Jinghua Chen

Polymeric micelles have attracted much attention in the field of anticancer drug delivery system because of their special properties. However, the slow drug release rate of micelles after reaching tumor cells is still considered to be a major problem. Therefore, we constructed a new orthoester-based pH-sensitive polyethylene glycol–hydroxydodecanoic acid (PAE) polymer to form doxorubicin-loaded micelles (DOX/PAE). DOX/PAE micelles with uniform particle size showed pH-sensitive drug release behavior in vitro . And the in vitro cytotoxicity studies showed that blank PAE micelles were nontoxic to cells while DOX/PAE micelles could inhibit the growth of tumor cells in a concentration-dependent manner. Furthermore, cellular uptake studies showed that DOX/PAE micelles were uptaken by tumor cells and transported into the nucleus to achieve the effect of killing tumor cells. The results of the uptake mechanism showed that clathrin and macrophage mediated endocytic pathways played important roles in internalization of DOX/PAE micelles. Altogether, the above results show that pH-sensitive PAE micelles have potential in anticancer drug delivery.

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JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION · 2021 · IF 3.517

Keratin-tannic acid complex nanoparticles as pH/GSH dual responsive drug carriers for doxorubicin

Jinsong Du,Lijuan Wang,Xiao Han,Jie Dou,Jiang Yuan,Jian Shen

Drug-loaded nanoparticles have been widely used in the field of tumor treatment due to their low side effects and reduced frequency of administration. In this study, pH and glutathione (GSH) dual-responsive keratin-tannic acid (TA) complex nanoparticles were established to trigger drug release under tumor microenvironments. Reductive keratin was first extracted using a reduction method. Then, keratin-TA complex nanoparticles (KNPs) were self-assembled via non-covalent interaction and further stabilized by self-crosslinking of thiols. This method was facile and green without chemicals during the whole procedure. KNPs exhibited pH and GSH dual responsiveness as well as charge reversibility in the simulated tumor microenvironment. The anticancer drug of doxorubicin (DOX) was loaded on KNPs by hydrophobicity and hydrogen bonds. Drug-loaded KNPs accelerated drug release under mimicked tumor microenvironments, performing high toxic against A549 cells while low toxic on normal cells. Besides, drug-loaded nanoparticles could be endocytosed by tumor cells. Based on these results, KNPs may serve as drug carriers for therapeutic delivery.

CAS / MDL: 70-18-8 1401-55-4
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EUROPEAN POLYMER JOURNAL · 2019 · IF 3.621

Polymeric micelles with aggregation-induced emission based on microbial ε-polylysine for doxorubicin delivery

Yanhai Li,Feng Gao,Jin Guo,Peng Ren,Zhenzhen Tian,Jianan Bai,Jie Hua

Natural polymers have shown special advantages in application as drug delivery carriers. However, microbial ε-polylysine seems to have been snubbed. In this study, we constructed a drug delivery system based on natural ε-polylysine. Amphipathic graft copolymer, methoxypoly(ethylene glycol)- graft -ε-polylysine-tetraphenylethylene (mPEG- g -Plys-TPE), was synthesized based on microbial ε-polylysine which was modified completely with PEG and TPE. MPEG- g -Plys-TPE could self-assemble into nanomicelles with stable shell-core structure. PEG served as the hydrophilic shell to provide long blood circulation and biocompatibility. TPE formed the hydrophobic core with aggregation-induced emission (AIE) effect to load drugs. The physical and chemical properties, including size distribution, morphology, stability and photoluminescent effect, were investigated in detail. In vitro drug release indicated pH-dependent patterns. Furthermore, cytotoxicity of doxorubicin (DOX)-loaded micelles against HT-29, HCT116 and SW480 was significantly higher than that of free DOX, which was explained by the mechanism of cellular uptake against tumor cells. In summary, all results suggested that mPEG- g -Plys-TPE as new type biomaterials exhibited great potential for drug delivery.

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JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY · 2019 ·Vol. 19 ·期 9 ·5463-5468 · IF 1.093

Ultrasound-Triggered Gas-Generating Doxorubicin Poly(lactic-co-glycolic acid)-Nanoparticles for Cancer Therapy

Zhang Nan,Liu Xinyang,Hou Ruirui,Zhang Jiangnan,Li Jia,Huo Pengchao,Xu Yue,Zhang Zhenzhong

The purpose of current research is to develop ultrasound-triggered gas-generating Doxorubicin PLGA nanoparticle for cancer therapy. Method: pH-sensitive PLGA nanoparticles (PLGANPs) was fabricated to deliver doxorubicin (DOX) and sodium bicarbonate (NaHCO3) using the water-in-oil-in-water (w/o/w) double emulsion method. Result: The nanoparticle with the size (650 nm) and high drug loading (15.8±2.3%) were successfully prepared and showed pH-responsive release characteristics. In vitro results indicate that DOX/NaHCO3@PLGANPs with ultrasound had higher inhibition and cell uptake on MCF-7 cells than free DOX and other formulation. In vivo animal experiments showed that after treatment of DOX/NaHCO3@PLGANPs with ultrasound, the relative tumor volume (0.63) of S180-tumor-bearing mice was lower than that of without ultrasound (0.81), DOX@PLGANPs (1.00) and Free DOX (1.12). Moreover, safety evaluation result indicated that DOX/NaHCO3@PLGANPs was safer than free DOX. In conclusion, the DOX/NaHCO3@PLGANPs was successfully developed and evaluated In vitro and In vivo. This drug delivery system will be a promising strategy for cancer therapy and diagnosis.

CAS / MDL: 9002-89-5
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PHARMACEUTICAL RESEARCH · 2019 ·Vol. 36 ·期 12 ·1-10 · IF 3.896

Transferrin Receptor Targeted Cellular Delivery of Doxorubicin Via a Reduction-Responsive Peptide-Drug Conjugate

Li Songtao,Zhao Hongling,Mao Xiaoxia,Fan Yanfang,Liang Xiujun,Wang Ruxing,Xiao Lijun,Wang Jianping,Liu Qi,Zhao Guiqin

Purpose Transferrin receptors (TfRs) are overexpressed in tumor cells but are scarce in normal tissues, which makes TfR an attractive target for drug treatment of cancer. The objective of this study was to evaluate the potential of BP9a (CAHLHNRS) as a peptide vector for constructing TfR targeted peptide-drug conjugates and selective drug delivery. Methods Doxorubicin (DOX) was connected to BP9a via a disulfide-intercalating linker to afford a reduction-responsive BP9a-SS-DOX conjugate. By using HepG2 human liver cancer cells and L-O2 normal hepatic cells as TfR over-expressing and low-expressing in vitro models, respectively, TfR mediated cellular uptake of this conjugate was studied by using flow cytometry and confocal laser scanning microscopy. The in vitro cytotoxicities of the conjugate against HepG2 and L-O2 cells were examined by cell counting kit-8 (CCK-8) assay to evaluate its tumorous specificity. Results Cellular uptake and TfR blockage test results showed that the BP9a-SS-DOX conjugate gained entry into HepG2 cells via endocytosis mediated by TfR and mainly accumulated in cytoplasm. The in vitro antiproliferative activity of this conjugate against HepG2 cells (IC 50 6.21 ± 1.12 μM) was approximately one-sixth of that of free DOX (IC 50 1.03 ± 0.13 μM). However, its cytotoxic effect on L-O2 cells was obviously reduced compared with that of free DOX. Conclusions The BP9a-SS-DOX conjugate showed specific antiproliferative activity against HepG2 liver cancer cells. Our study suggests that BP9a has the potential to target chemotherapeutic agents to tumor cells over-expressing TfR and facilitate selective drug delivery.

CAS / MDL: 25316-40-9
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Biomaterials Science · 2019 ·Vol. 7 ·期 11 ·4615-4623 · IF 5.251

Doxorubicin-loaded nanoscale metal–organic framework for tumor-targeting combined chemotherapy and chemodynamic therapy

Ting Xue,Caina Xu,Yu Wang,Yanbing Wang,Huayu Tian,Yingchao Zhang

Doxorubicin (DOX) as a traditional chemotherapy drug is restricted in clinical applications due to its poor therapeutic activity and severe side effects. Herein, we prepared a metal–organic framework (MOF) MIL-100 by a microwave-assisted synthesis and DOX was loaded in MIL-100 and then, hyaluronic acid (HA) was modified on the surface of MIL-100 to give DMH NPs. The DMH NPs possessed the following advantages: (1) MIL-100 could serve as a drug carrier with a high DOX loading efficiency; MIL-100 could also generate a hydroxyl radical (˙OH) in the presence of H2O2 for chemodynamic therapy (CDT) via a Fenton-like reaction. (2) To improve the dispersibility of MIL-100, HA was modified on the surface of MIL-100, which could endow MIL-100 with a targeting ability towards tumor tissues. (3) DMH NPs could enhance antitumor efficacy and reduce drug-related toxicity though the combination of chemotherapy and chemodynamic therapy. DMH NPs have enormous potential as a candidate for reducing the systemic toxicity and improving the treatment effect for breast cancer.

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ONCOLOGY REPORTS · 2019 ·Vol. 42 ·期 1 ·313-320 · IF 3.041

miR‑92a contributes to cell proliferation, apoptosis and doxorubicin chemosensitivity in gastric carcinoma cells

Xuan‑Chen Tao,Xin‑Yu Zhang,Shi‑Bo Sun,De‑Quan Wu

MicroRNAs (miRNAs) are a class of short noncoding RNAs that negatively regulate gene expression and act as oncogenes or tumor suppressors. Numerous miRNAs have been reported be associated with the occurrence and development of gastric carcinoma (GC). For instance, miR‑92a has been observed to be overexpressed in GC; however, the precise mechanisms underlying the role of miR‑92a in GC and its role in clinical therapy require further investigation. In the present study, it was reported that miR‑92a expression was significantly upregulated in GC tissues compared with in adjacent tissues. Additionally, suppression of miR‑92a significantly reduced SGC7901 cell viability as demonstrated by a Cell Counting Kit‑8 and colony formation assays. Suppression of miR‑92a inhibited SGC7901 cell proliferation as determined by Ki‑67 immunofluorescence staining, and the expression levels of proliferating cell nuclear antigen, cyclin dependent kinase (CDK)4 and CDK6, and increased that of p53. In addition, we reported that suppression of miR‑92a induced apoptosis in SGC7901 cells. Furthermore, bioinformatics analysis identified that ING2 as a potential target of miR‑92a. Downregulation of miR‑92a significantly increased ING2 expression at the mRNA and protein levels. A dual‑luciferase reporter assay validated a direct binding site of miR‑92a on ING2. In addition, SGC7901 cells with suppression of miR‑92a were more sensitive to doxorubicin treatment. Knockdown of miR‑92a reduced the half‑maximal inhibitory concentration of doxorubicin from 147.6 nM to 82.1 nM in SGC7901 cells. Knockdown of miR‑92a also reduced SGC7901 cell survival under doxorubicin stimulation. Furthermore, SGC7901 cells with suppression of miR‑92a harbored a greater number of DNA damage foci upon doxorubicin treatment compared with in control cells. The findings of the present study revealed that miR‑92a contributes to cell proliferation, apoptosis and doxorubicin chemosensitivity in GC cells, which suggests a potential therapeutic strategy for the treatment of GC.

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