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Doxorubicin
APPLIED CATALYSIS B-ENVIRONMENTAL · 2022 · IF 24.319

Nitrogen doped carbon-distributed and nitrogen-stabilized ultrafine FeM (M = Pd, Pt, Au) nanoclusters for doxorubicin detoxification

Haoyang Fu,Meirong Li,Qianyu Xu,Guoliang Chen,Yunjie Zou,Weixian Zhang,Shuzhou Li,Lan Ling

Downsizing supported metal of Fe 0 -based materials in dealing with ever-growing pharmaceutical contamination issues are highly desired but still challenging. Herein, we develop a modular design protocol to synthesize a family of ultrafine alloy nanoclusters embedded in a nitrogen-enriched carbon framework (NEC@FeM (M=Pd, Pt, Au)). Engineering the fine structure of nitrogen-enriched carbon and interfacial interaction with bimetallic nanoclusters largely suppresses bimetallic overgrowth, eventually producing supported ultrafine (< 4 nm), highly dispersed, well-alloyed nanoclusters. The alloying Fe 0 with M for ultrafine nanoclusters optimize the electron flow, chemical stability, and catalytic property, resulting in the obtained NEC@FeM exhibiting excellent doxorubicin (DOX) degradation performance. Density functional theory calculation combined with experimental results attribute the outstanding DOX degradation ability of NEC@FePd originally to the synergistic effect of enhanced DOX affinity and efficient electrons transfer from Fe to DOX. This work provides a paradigm for the design of ultrafine Fe 0 -based nanocluster with application in pollution control.

CAS / MDL: 527-31-1
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International Journal of Nanomedicine · 2022 · IF 7.033

Tumor Microenvironment Multiple Responsive Nanoparticles for Targeted Delivery of Doxorubicin and CpG Against Triple-Negative Breast Cancer

Fenfen Gu,Chuling Hu,Wei Cao,Chao Li,Qingming Xia,Yuan Gao,Yan Liu,Shen Gao

Introduction Currently, the main treatment for advanced breast cancer is still chemotherapy. Immunological and chemical combination therapy has a coordinated therapeutic effect and achieves some efficacy. However, the immunosuppressive tumor microenvironment is a major cause for the failure of immunotherapy in breast cancer. CpG oligodeoxynucleotides can activate the tumor immune microenvironment to reverse the failure of immunotherapy. Methods In this study, we designed an amphiphilic peptide micelle system (Co-LMs), which can targeted delivery of the immune adjuvant CpG and the chemotherapeutic drug doxorubicin to breast cancer tumors simultaneously. The peptide micelle system achieved tumor microenvironment pH and redox-sensitive drug release. Results and Discussion Co-LMs showed 2.3 times the antitumor efficacy of chemotherapy alone and 5.1 times the antitumor efficacy of immunotherapy alone in triple-negative breast cancer mice. Co-LMs activated cytotoxic CD8+ T lymphocytes and CD4+ T cells in mice to a greater extent than single treatments. We also found that Co-LMs inhibited the metastasis of circulating tumor cells in the bloodstream to some extent. These results indicate that the Co-LMs offer a promising therapeutic strategy against triple-negative breast cancer.

CAS / MDL: 25952-53-8 6066-82-6
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS · 2021 · IF 4.539

Self-assembly of polymer-doxorubicin conjugates to form polyprodrug micelles for pH/enzyme dual-responsive drug delivery

Mengna Zhang,Shujing Zhang,Kun Zhang,Zongyuan Zhu,Yalei Miao,Yudian Qiu,Panke Zhang,Xubo Zhao

Functionality of polymers is crucially fundamental to polymers. However, the application of polymers faces great challenges due to the insufficient function of hydrophobic chain, especially in drug delivery. One novel approach to solve this dilemma involves the use of medicated hydrophobic chains. Herein, the polymer-doxorubicin conjugates are synthesized from hydrophilic copolymer and hydrophobic chain composed of doxorubicin (DOX). DOX, a common hydrophobic anticancer drug , is used to serve as a hydrophobic pendant for inducing self-assembly of polymer-doxorubicin conjugates. The self-assembly of polymer-drug conjugates is employed to encapsulate the unreacted drug for the first time and form drug-loaded polyprodrug micelles that possess a low critical micelle concentration (CMC), which improves the use efficiency of expensive drug. The detachment of DOX moieties from polymer-doxorubicin conjugates caused by amidase facilitates the disintegration of DOX-loaded polyprodrug micelles to trigger the enhanced release of DOX in a slightly acidic medium. It is demonstrated that the DOX-loaded polyprodrug micelles have a higher suppression against cancer cells in in vitro investigations. This work thus proposes a strategy to modify the poor functionality of polymer-based nanostructures , through designing the medicated hydrophobic chains. This strategy facilitates the potential application of polymer-drug conjugates and provides profound insights into the effect of medicated polymer on drug delivery system.

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PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY · 2020 · IF 2.169

Mitochondrial targeted doxorubicin derivatives delivered by ROS-responsive nanocarriers to breast tumor for overcoming of multidrug resistance

Xin-Cheng Zhong,Ming-Han Shi,Hui-Na Liu,Jie-Jian Chen,Tian-Tian Wang,Meng-Ting Lin,Zhen-Tao Zhang,Yi Zhou,Yi-Ying Lu,Wen-Hong Xu,Jian-Qing Gao,Dong-Hang Xu,Min Han,Yi-Ding Chen

CAS / MDL: 68-12-2
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JOURNAL OF MATERIALS SCIENCE · 2020 ·Vol. 55 ·期 35 ·16718-16729 · IF 3.553

A novel high doxorubicin-loaded Fe3O4@void@ZnO nanocomposite: pH-controlled drug release and targeted antitumor activity

Wang Chen,Wen Hao,Guo Hailing,Wang Xueyan,Shen Yuhua,Xie Anjian

A novel ferroferric oxide (Fe 3 O 4 )@void@zinc oxide (ZnO) nanocomposite was constructed through a template-assisted selective etching method. The experiment results showed that the magnetic saturation value of nanocomposite could reach to 44.07 emu g −1 , indicating the favorable magnetic targeting function. The presence of the void endowed the nanocomposite with high drug doxorubicin (DOX) loading capacity (85.65 μg mg −1 ). The pH-sensitive drug release was realized due to the gating effect of ZnO, and the DOX release rates were 92.7%, 60.8% and 23.4% at the pH values of 5.0, 6.5 and 7.4, respectively (37 °C). Besides, the Fe 3 O 4 @void@ZnO-DOX exhibited desirable antitumor effects attributed to their cellular uptake and above advantages. Therefore, the Fe 3 O 4 @void@ZnO nanocomposite may serve as a promising drug carrier in cancer therapy and other biomedical applications.

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NANOTECHNOLOGY · 2020 ·Vol. 31 ·期 19 ·195103 · IF 3.551

Doxorubicin-loaded pH-responsive nanoparticles coated with chlorin e6 for drug delivery and synergetic chemo-photodynamic therapy

Junlong Liang,Xiaokang Jin,Biling Chen,Jinhua Hu,Qianwei Huang,Junmin Wan,Zhiwen Hu,Bing Wang

The integration of chemotherapy drugs and photosensitizers to form versatile nanoplatforms for achieving chemo-photodynamic synergetic therapy has shown great superiority in tumor theranostic applications. We constructed pH-responsive nanoparticles (DOX/PB NPs) encapsulating the chemotherapeutic drug doxorubicin (DOX) into the cores of PLGA NPs coated with bovine serum albumin (BSA) via a water-in-oil (W/O/W) emulsion method. A simple and efficient chemo-photodynamic synergetic nanoplatform (DOX/PB@Ce6 NPs) was obtained by the adsorption of photosensitizer chlorin e6 (Ce6) onto the surface of the DOX/PB NPs. With optimal size, pH-responsive drug release behavior and excellent singlet oxygen production, the DOX/PB@Ce6 NPs have the potential to enhance anti-tumor efficiency. The cellular uptake, cytotoxicity, chemo-photodynamic synergetic effect and biocompatibility of the NPs were evaluated based on HeLa cells via in vitro experiments. The in vitro chemo-photodynamic synergetic experiments indicated that the DOX/PB@Ce6 NPs had remarkable cancer cell killing efficiency under laser irradiation. Notably, by hemolysis assay, all the NPs displayed excellent blood compatibility and were expected to be applicable for intravenous injection. In summary, the designed DOX/PB@Ce6 NPs multifunctional theranostic nanoplatform had excellent reactive oxygen species generation and would be a potential therapeutic platform for chemo-photodynamic synergetic therapy.

CAS / MDL: 26780-50-7
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PLoS One · 2020 ·Vol. 15 ·期 6 ·e0235090 · IF 2.74

Doxorubicin-loading core-shell pectin nanocell: A novel nanovehicle for anticancer agent delivery with multidrug resistance reversal

Jiabi Ouyang,Mohui Yang,Tian Gong,Jinlai Ou,Yani Tan,Zhen Zhang,Sha Li

Tumor is a prevalent great threat to public health worldwide and multidrug resistance (MDR) of tumor is a leading cause of chemotherapy failure. Nanomedicine has shown prospects in overcoming the problem. Doxorubicin (DOX), a broad-spectrum anticancer drug, showed limited efficacy due to MDR. Herein, a doxorubicin containing pectin nanocell (DOX-PEC-NC) of core-shell structure, a pectin nanoparticle encapsulated with liposome-like membrane was developed. The DOX-PEC-NC, spheroid in shape and sized around 150 nm, exerted better sustained release behavior than doxorubicin loading pectin nanoparticle (DOX-PEC-NP) or liposome (DOX-LIP). In vitro anticancer study showed marked accumulation of doxorubicin in different tumor cells as well as reversal of MDR in HepG2/ADR cells and MCF-7/ADR cells caused by treatment of DOX-PEC-NC. In H 22 tumor-bearing mice, DOX-PEC-NC showed higher anticancer efficacy and lower toxicity than doxorubicin. DOX-PEC-NC can improve anticancer activity and reduce side effect of doxorubicin due to increased intracellular accumulation and reversal of MDR in tumor cells, which may be a promising nanoscale drug delivery vehicle for chemotherapeutic agents.

CAS / MDL: 57-88-5 112-80-1
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Nano Today · 2020 · IF 16.907

Carrier-free nanoassembly of doxorubicin prodrug and siRNA for combinationally inducing immunogenic cell death and reversing immunosuppression

Senbiao Chen,Dongdong Li,Xiaojiao Du,Xinyu He,Mengwen Huang,Yang Wang,Xianzhu Yang,Jun Wang

Doxorubicin (DOX) can elicit antitumor immunity responses by inducing immunogenic cell death (ICD) but also triggers upregulated expression of various immunosuppressive genes to counteract the ICD effect. To resolve this conflict, a carrier-free nanoassembly of acid-activatable DOX prodrug and small interfering RNA (siRNA) was developed to combinationally induce ICD and reverse immunosuppression. The carrier-free nanoassembly with rather high drug contents (4.13 % for siRNA and 21.67 % for DOX) was formed via cooperative π–π stacking and electrostatic interactions. The formed nanoassembly, termed as [email protected] :siRNA, possessed a well-defined nanostructure: a core consisting of DOX plus siRNA and a shell consisting of polyethylene glycol (PEG). It has been demonstrated that this carrier-free nanoassembly carrying siRNA targeting PD-L1 can significantly increase tumor-infiltrating T lymphocytes, improve interferon-γ (IFN-γ) expression, and ultimately strengthen the ICD effect of the DOX prodrug, resulting in a significantly enhanced anticancer immune response and superior tumor growth inhibition. In addition, carrier-free nanoassembly [email protected] :siRNA can also be conveniently extended as a general strategy to combine chemotherapy and immunotherapy, providing a facile avenue for improving cancer chemoimmunotherapy.

CAS / MDL: 7693-46-1
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ChemNanoMat · 2022 ·Vol. 8 ·期 12 ·e202200424 · IF 3.82

FeOCl Nanodots and Doxorubicin Co-loaded Polymer Nanoparticles for Glutathione/pH-responsive Chemodynamic Therapy/Chemotherapy of Tumors

Lihui Yuwen,Yue Zhang,Huayu Xiao,Hang Xiao,Xiao Li,Wenjing Yang,Zhaoxia Yang,Heng Dong,Lianhui Wang

Graphical FeOCl nanodots were prepared by a ball-milling method and used as novel Fenton agents. Glutathione/pH dual-responsive polymer nanoparticles were synthesized by co-polymerization of acrylic acid and 3-methacrylamido dopamine with a cross-linker containing disulfide bonds, which can load FeOCl nanodots and doxorubicin to form a multifunctional nanoplatform for efficient chemodynamic therapy/chemotherapy. Chemodynamic therapy (CDT) based on the Fenton reaction has been considered as a promising solution for the treatment of tumors. However, the limited therapeutic efficacy and lack of responsive release of Fenton agents still hinder the further application of CDT. To this end, we designed a disulfide bond (−S−S−) cross-linked polymer nanoparticles (poly(AA-co-DMA), PAD) to load FeOCl nanodots (FeOCl NDs) and doxorubicin (DOX) with the surface coating of bovine serum albumin (BSA) to prepare glutathione (GSH)/pH-responsive PAD-FeOCl/DOX@BSA nanoparticles (PFDB). In the tumor microenvironment (TME) with abundant GSH and acidic pH, the −S−S− bond in PFDB can be reduced and the linkage between the polymer chains is broken down, which facilitates the controlled release of FeOCl NDs and DOX. Both in vitro and in vivo experimental results showed that PFDB can serve as a GSH/pH-responsive nanoagent for the effective killing of 4T1 tumor cells by combined CDT/chemotherapy. This study provides a promising TME-responsive nanoagent with dual therapeutic modes for the effective treatment of tumors.

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ACS Applied Nano Materials · 2023 · IF 5.9

Aptamer- and Lauric Acid-Modified Au Nanocrystals for Targeted Doxorubicin Delivery and Combined Phototherapy, Chemotherapy, and Immunotherapy

Li Sun,Tao Li,Binglin Li,Yingshu Guo

A bispecific thermosensitive system was created to deliver drugs and aid T cells in identifying cancer cells for enhancing the tumor-killing effect. Among various nanocarriers, gold nanocages (AuNCs) were selected as the photothermal agents for photothermal therapy (PTT) due to their distinctive hollow and void structures, which make them ideal carriers throughout the therapy. To achieve controlled drug release under near-infrared radiation, lauric acid (LA) was chosen as the “gatekeeper”, responding to a temperature stimulus. Bispecific aptamers with surface modifications were utilized to increase the intracellular drug content while triggering the immune system to eliminate the cancer cells. The homologous targeting ability of AuNCs/LA/ doxorubicin (DOX)/Apt resulted in a high tumor site aggregation. PTT-induced in situ tumor heat elimination and increased tumor cell immunogenicity upon exposure to laser irradiation. Consequently, the smart nano platform not only destroyed the tumor cells through PTT and chemotherapy but also formed a T cell–cancer cell complex at the tumor site, causing the immune cells to precisely identify the tumor and achieve in situ activation of the immune response at the tumor site. The proposed strategy was a classic “cocktail therapy”.

CAS / MDL: 25952-53-8 6066-82-6
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Materials Science & Engineering C-Materials for Biological Applications · 2017 · IF 4.164

Multimodal nanoporous silica nanoparticles functionalized with aminopropyl groups for improving loading and controlled release of doxorubicin hydrochloride

Xin Wang,Chang Li,Na Fan,Jing Li,Zhonggui He,Jin Sun

The purpose of this study was to develop amino modified multimodal nanoporous silica nanoparticles (M-NSNs-NH 2 ) loaded with doxorubicin hydrochloride (DOX), intended to enhance the drug loading capacity and to achieve controlled release effect. M-NSNs were functionalized with aminopropyl groups through post-synthesis. The contribution of large pore sizes and surface chemical groups on DOX loading and release were systemically studied using transmission electron microscope (TEM), nitrogen adsorption/desorption measurement, Fourier transform infrared spectroscopy (FTIR), zeta potential analysis, X-ray photoelectron spectroscopy (XPS) and ultraviolet spectrophotometer (UV). The results demonstrated that the NSNs were functionalized with aminopropyl successfully and the DOX molecules were adsorbed inside the nanopores by the hydrogen bonding. The release performance indicated that DOX loaded M-NSNs significantly controlled DOX release, furthermore DOX loaded M-NSNs-NH 2 performed slower controlled release, which was mainly attributed to its stronger hydrogen bonding forces. As expected, we developed a novel carrier with high drug loading capacity and controlled release for DOX.

CAS / MDL: 919-30-2 78-10-4
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Materials Today Bio · 2023 · IF 8.2

Morphologically transformable peptide nanocarriers coloaded with doxorubicin and curcumin inhibit the growth and metastasis of hepatocellular carcinoma

Yun Liu,Yunxia Liu,Xinyu Sun,Yue Wang,Changqing Du,Jingkun Bai

In tumor treatment, the highly disordered vascular system and lack of accumulation of chemotherapeutic drugs in tumors severely limit the therapeutic role of nanocarriers. Smaller drug-containing nanoparticles (NPs) can better penetrate the tumor but are easily removed, which severely limits the tumor-killing properties of the drug. The chemotherapeutic medication doxorubicin (DOX) is highly toxic to the heart, but this toxicity can be effectively mitigated and the combined anticancer effect can be enhanced by clinically incorporating curcumin (CUR) as part of the dual therapy. We designed a small-molecule peptide, Pep1, containing a targeting peptide (CREKA) and a pH-responsive moiety. These NPs can target the blood vessels in tumor microthrombi and undergo a morphological shift in the tumor microenvironment. This process enhances the penetration and accumulation of drugs, ultimately improving the effectiveness of cancer treatment. In vitro and in vivo experiments demonstrated that this morphological transformation allowed rapid and effective drug release into tumors, the effective inhibition of tumor angiogenesis, and the promotion of tumor cell apoptosis, thus effectively killing tumor cells. Our findings provide a novel and simple approach to nhibit the growth and metastasis of hepatocellular carcinoma.

CAS / MDL: 458-37-7
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