查找使用阿拉丁产品的科研文献

A novel self-assembled galactose/polysuccinimide-coated hydroxyapatite nanocarriers for targeted hepatic doxorubicin delivery

Junxia Gao,Wenhui Zhang,Qiang Wang,Jingdan Cao,Ying Zhu,Guifang Liu,Youbiao Jia,Fengbo Yu

To mitigate the adverse effects of doxorubicin (DOX) during the treatment of liver cancer, this study aimed to develop a novel DOX-encapsulated active-targeted nanodelivery system. The auxiliary materials hydroxyapatite (HAP), polysuccinimide (PSI), galactose-modified polyethylene glycol (Gal-PEG), PSI covalently linked with three different mole ratios of polyethylene glycol (PEG-PSIs), and galactose covalently linked with PEG-PSIs (Gal-PSIs) were synthesized and structurally characterized. The Box-Behnken and Three-Level Factorial Design response surface methodologies were employed to optimize the formulations and synthesis protocols for DOX@HAP/PSI (DOX@DC, where DC denotes the drug carrier), DOX@PEG-DCs, and DOX@Gal-DCs. The in vitro drug release and in vivo tissue distribution of each formulation were examined. Furthermore, in vitro studies were conducted to examine the effects of these formulations on the proliferation, apoptosis, and migration of Huh-7 liver cancer cells. The formulations and synthesis protocols for different DOX-based preparations were optimized. All nanoparticles gradually released DOX at pH levels >5, with the release rate increasing with the pH value. Among the tested formulations, DOX@Gal-DC20 (mole ratio of Gal-PEG to PSI = 1:20) showed the best hepatic targeting in mice in vivo. Furthermore, in vitro pharmacodynamic experiments indicated that Gal-DC20 had low cytotoxicity, could be taken up by cancer cells, and could significantly inhibit the proliferation of Huh-7 cells. Hemolysis experiments confirmed that none of the prepared formulations induced hemolysis. The novel nanodelivery system established in the study (DOX@Gal-DC) is simple to prepare and shows significant hepatic targeting.

Repurposing the hERG activator NS-1643 as a ferroptosis-targeting therapeutic against doxorubicin cardiotoxicity

Xie-Huang Sheng,Lin-Song Teng,Xin-Hui Wang,Li-Qi Jiang,Xue-Cheng Sun,Jin-Long Mao,Lei Zhang

Cardiovascular diseases arise from intertwined cell-death and stress-response pathways, underscoring the need for therapeutics that extend beyond single-target mechanisms. Seeking drug-repurposing opportunities within existing cardiovascular agents, we screened clinically explored compounds for unrecognized cytoprotective activity and identified the hERG/Kv11.1 activator NS-1643—originally developed as an antiarrhythmic candidate—as a potent ferroptosis inhibitor. NS-1643 broadly suppressed GPX4 inhibitor–induced ferroptotic death across diverse cell types, whereas other hERG modulators were inactive, and neither pharmacologic blockade nor genetic silencing of hERG altered its efficacy, demonstrating that its protective mechanism is independent of ion-channel modulation. Mechanistic profiling showed that NS-1643 does not restore canonical ferroptosis-defense systems, but instead operates as a direct lipid-peroxyl radical trapper, supported by radical-scavenging assays and density functional theory revealing an energetically favorable hydrogen-atom transfer mediated by its ortho-amino–phenolic motif. In a murine model of doxorubicin (DOX) cardiotoxicity, NS-1643 markedly improved survival, preserved systolic performance, and reduced myocardial injury, fibrosis, and 4-HNE accumulation, whereas the comparator hERG agonist NS-3623 conferred no benefit. These findings reposition NS-1643 as a dual-mechanism, ferroptosis-targeting cardioprotective agent and illustrate how drug repurposing can reveal multi-target therapeutic potential within existing cardiovascular chemical space, offering a promising strategy to mitigate anthracycline-induced cardiac injury.

Carrier-free doxorubicin nanomedicine integrates chemotherapy and chemodynamic therapy to achieve anti-tumor efficacy

Min Liu,Xin Hu,Siyi Liu,Jingya Xiu,Dan Li,Jiulong Zhang,Xiuli Zhao

Nanomedicines have been constructed to enhance the efficacy and safety of traditional anti-cancer drugs. However, the clinical translation of these nanomedicines was hindered by the complexity of carrier materials and functional integration. In this study, a carrier-free nanomedicine composed of doxorubicin (DOX), Cu 2+ and siRNA of GPX4 was constructed for combination therapy of tumors. DOX, Cu 2+ , and siRNA were assembled through multiple forces and decorated with hyaluronic acid (HA) to prepare tumor targeted carrier-free nanomedicines (HDCS). The HA coating on the surface of HDCS ensured specific tumor targeting, and the released drugs triggered by acidity could eliminate tumor cells. The nanomedicine showed significant anti-cancer efficiency and quite reduced side effects in the breast cancer model when compared with DOX solution. HDCS treatment led to significant accelerated production of ROS, reduced GPX4 expression, and sustained decrease in GSH at tumor sites, ultimately forming a powerful chemodynamic effect enhancing circuit. The HDCS provides an effective strategy for tumor combination therapy with good clinical translation and application potential.

Preparation of Photoresponsive Doxorubicin/ICG Microfluidic Nanoparticles and Their Enhanced Anti-B16F10 Melanoma Activity

Xia Cao,Zhangxintian Ding,Yize Lv,Xuedi Weng,Hongran Huang,Jinghan Li,Ximing Xu,Qilong Wang

The clinical treatment of melanoma is severely limited by the rapid development of intrinsic and acquired resistance to conventional chemotherapeutic drugs, such as doxorubicin (DOX), as well as their severe, dose-limiting systemic toxicities. To address this issue, we developed a novel nanoplatform for near-infrared (NIR)- activatable nanoplatform leveraging microfluidics as a precision fabrication tool to overcome the limitations of conventional nanocarrier synthesis, including poor batch-to-batch reproducibility, heterogeneous size distribution, and suboptimal drug co-loading. A photocrosslinkable copolymer, Pluronic F127 diacrylate (F127DA), was synthesized and processed using a custom-designed dual-zone microfluidic chip that integrates sequential flow-focusing and turbulent mixing. This approach enabled the one-step, highly controlled co-encapsulation of DOX and indocyanine green (ICG) into monodisperse F127DA nanoparticles (43.9 ± 0.6 nm, polydispersity index: 0.18) with superior encapsulation efficiency (DOX: 60.4%) and drug loading (12.8%). Upon NIR irradiation, the resulting DOX/ICG@F127DA nanoparticles mediated synergistic chemo-photothermal-photodynamic therapy, as evidenced by potent cytotoxicity (melanoma cell viability reduced to 35%), a significant 3.1-fold increase in reactive oxygen species (ROS) generation, and effective inhibition of cell migration (wound closure rate of 17.2% compared to 21.7% with free DOX). Mechanistically, the NIR-triggered ROS burst induced mitochondrial-mediated apoptosis by dysregulating the Bax/Bcl-2 ratio (increased by 2.7-fold), culminating in an apoptosis rate of up to 68.3%. Collectively, this work establishes microfluidics as a robust and scalable platform for engineering complex nanomedicines and delineates the “NIR light–ROS–Bax/Bcl-2” axis as a critical molecular pathway for overcoming chemoresistance in melanoma. Download: Download high-res image (231KB) Download: Download full-size image

Postbiotic metabolites from Bifidobacterium adolescentis alleviates doxorubicin‑induced aging in canine vascular endothelial cells

Hongchen Jin,Huasong Bai,Tong Liu,Hengyan Wang,Yunliang Li,Zhanzhong Wang

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

A charge-reversible hyaluronic acid prodrug nanoplatform for synergistically enhanced tumor-targeted doxorubicin delivery

Yulong Yan,Jing Shi,Zhenqiao Zheng,Xiaojing Shi,Xubo Zhao

Conventional nanocarriers often face challenges of insufficient tumor specificity and poor cellular internalization. To overcome these limitations, we developed an all-in-one prodrug nanoplatform based on hyaluronic acid (HA) that synergistically integrates active targeting, pH-responsive charge reversal, and controlled drug release. Doxorubicin (DOX) was covalently conjugated to oxidized HA via a pH-sensitive imine bond, while a charge-reversal polymer (PLL-DMMA) was grafted onto the HA backbone. This design enables CD44-mediated active targeting toward cancer cells. Crucially, the nanoplatform exhibits a smart charge-reversal characteristic: maintaining a negative surface charge (−32.8 mV) at physiological condition (pH 7.4) for extended circulation, while switching to positive (+16.5 mV) in the acidic tumor microenvironment (pH 6.5) to enhance cellular uptake. In vitro studies demonstrated significantly improved internalization in CD44-overexpressing MKN-45 cells compared to SNU-216 cells with low CD44 expression. The release profile showed high stability at pH 7.4 (<5% release in 5 days) and rapid drug release at endo/lysosomal pH (61.6% at pH 5.0). Cytotoxicity assays confirmed enhanced efficacy of the charge-reversed formulation, with lower IC 50 values in both cell lines. This multifunctional prodrug nanoplatform represents a promising strategy for precision cancer chemotherapy through synergistic enhancement of tumor targeting and intracellular drug delivery. In this study, we developed an all-in-one prodrug nanoplatform based on hyaluronic acid (HA) that synergistically integrates active targeting, pH-responsive charge reversal, and controlled drug release. In vitro studies demonstrated significantly improved internalization in CD44-overexpressing MKN-45 cells compared to SNU-216 cells with low CD44 expression. Cytotoxicity assays confirmed enhanced efficacy of the charge-reversed formulation, with lower IC50 values in both cell lines. This multifunctional prodrug nanoplatform represents a promising strategy for precision cancer chemotherapy through synergistic enhancement of tumor targeting and intracellular drug delivery. Download: Download high-res image (132KB) Download: Download full-size image

The revolutionizing osteosarcoma therapy of carbon monoxide and doxorubicin synergy via mesoporous silica nanoparticles

Yating Lian,Junyi Zhou,Wei Li,Zhijie Yuan,Minghui Zhong,Tian Wei,Huishan Liang,Shicong Yang,Li Ding,Li-Ming Zhang,Fen Wang

Chemoresistance is the main cause of recurrence and metastasis in osteosarcoma patients; therefore, efficient therapeutic measures need to be developed to reverse chemoresistance. In this study, we designed and synthesized selenium-hybrid degradable hollow mesoporous silica nanoparticles (SeNPs) to simultaneously encapsulate doxorubicin (DOX) and carbon monoxide (CO)-releasing molecule-3 (CORM-3), and modified their surfaces with polyethylene glycol (PEG) via disulfide bonds (SeNP-PEG@DOX-CO). Subsequently, after incubation with SeNP-PEG@DOX-CO, DOX was effectively delivered into 143B cells, and CO was released in the mitochondria under the stimulation of high concentrations of glutathione (GSH) and reactive oxygen species (ROS). All in vitro anticancer functional experiments and animal experiments confirmed that DOX had CO-enhanced antitumor efficacy and that CO cooperated with chemotherapeutic drugs to resist tumors. Meanwhile, we provided for the first time a combined proteomic and metabolomic landscape of CO reversing chemotherapy resistance in osteosarcoma. This study revealed a revolutionizing osteosarcoma therapy to treat resistance for chemotherapy.

Charge-convertible MnO2-coated liposomal nanocarriers boost doxorubicin delivery for potentiated breast cancer chemotherapy

Chuanchuan He,Shuaizhi Kong,Jie Zhang,Lihua Chen,Guoqing Zhang,Limin Jin,Xiaojuan Zhang,Baoyue Ding

Efficient completion of the CAPIR (circulation, accumulation, penetration, internalization, and release) cascade is essential for nanosystems to achieve satisfactory therapeutic efficacy and prognosis. Herein, we fabricated a manganese dioxide (MnO 2 )-coated cationic liposomal nanocarrier (MnO 2 @CLDOX) for enhanced doxorubicin (DOX) delivery via a multistage strategy. The anionic MnO 2 shell conferred negative zeta potential, enabling prolonged blood circulation and reduced systemic toxicity. In the tumor microenvironment, MnO 2 selectively decomposed under acidic pH and high hydrogen peroxide, exposing cationic CLDOX and generating O 2 . Cationic CLDOX facilitated cellular uptake via electrostatic interactions with tumor cell membranes. Meanwhile, O 2 alleviated tumor hypoxia, downregulated hypoxia-inducible factor-1 α , decreased collagen deposition, and improved extracellular matrix permeability, thus boosting drug penetration. Collectively, MnO 2 @CLDOX enhanced DOX delivery efficiency through synergistic mechanisms, achieving superior therapeutic efficacy against breast cancer.

Dual-targeted nanomedicine delivering doxorubicin and nitric oxide for tumor immunomodulation and synergistic therapy

Xingzhou Peng,Wei Chen,Shuyu Li,Xiaomin Ma,Yanfeng Dai,Yan Wang,Changqiang Xie,Yazhe Xiao,Hesong Han,Yumiao Zhang,Junjie Wang

Cancer therapeutic efficacy is significantly influenced by tumor immunosuppressive environment possibly induced by chemotherapy-mediated tumor-intrinsic programmed death-ligand 1 (PD-L1) upregulation or tumor-associated macrophages (TAMs) promoting additional PD-L1 expression on tumor cells through distinct paracrine signaling pathways. To overcome this dual resistance mechanism, we developed a hyaluronic acid-functionalized nanoplatform for co-delivering DOX and nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine (SNAP), termed HA-DS@PLGA. This system facilitates dual targeting of CD44-overexpressing tumor cells and TAMs via HA-mediated recognition while the PLGA core ensures sustained release of both agents. SNAP-derived NO effectively attenuates DOX-induced PD-L1 expression through NO-mediated signaling disruption while synergistically potentiating DOX's immunogenic cell death effects. In TAMs, the system synergistically eliminates M2 macrophages and reprograms residual macrophages toward the tumoricidal M1 phenotype via PI3K-AKT signaling. In 4T1-tumor-bearing mouse models, HA-DS@PLGA achieved 95.8%, 94.5%, and 88.4% tumor inhibition versus PBS, HA-S@PLGA (SNAP alone), and HA-D@PLGA (DOX alone), respectively. Meanwhile, HA-DS@PLGA elicited systemic immunity, as evidenced by enhanced dendritic cell maturation, increased cytotoxic T lymphocyte infiltration, elevated IFN-γ production, and downregulation of PD-L1. By simultaneously targeting tumor-intrinsic and microenvironment-mediated immunosuppression, HA-DS@PLGA overcomes multifaceted resistance mechanisms and amplifies antitumor immunity, offering a promising paradigm for combinatorial cancer nanomedicine.

Optimizing doxorubicin prodrug albumin nanoparticles through tailored alkyl chain lengths and optimized linker chemistry

Hongkai Fang,Jingxuan Zhang,Jialin Xing,Yuebin Dai,Yanzhong Hao,Wenjing Wang,Zhiyu Kuang,Mingyang Han,Zhonggui He,Bingjun Sun,Jin Sun

Albumin-based nanoparticle (ANP) drug delivery systems have achieved significant clinical success. However, the low affinity between Doxorubicin (DOX) and human serum albumin (HSA) hinders the formation of stable nanoparticles. In our studies, we initially conjugated DOX to disulfide bond-containing fatty alcohols via carboxamide bond to systematically evaluate the impact of carbon chain length (C4, C8, C12, C20) on the binding affinity between DOX and HSA. Notably, when the carbon chain length of fatty alcohols reached eight (C8), DOX exhibited strong binding affinity to HSA. However, these prodrugs exhibited weak cytotoxicity, indicating insufficient DOX release due to the stable carboxamide bond. To address this issue, we further replaced the stable carboxamide bond with relative active carbamate bond (DOX-OCO-C 8 ). Under high glutathione (GSH) conditions in tumor cells, DOX-OCO-C 8 ANPs exhibited accelerated hydrolytic activity and efficient release of DOX. The ANPs significantly improved the pharmacokinetic profile and antitumor efficacy of DOX while reducing systemic toxicity. Our findings suggested optimizing alkyl chain lengths and linker chemistry offers a promising strategy for developing effective and safe DOX prodrug ANPs.

Preparation and evaluation of SiO2-deposited stearic acid-g-chitosan nanoparticles for doxorubicin delivery

Hong Yuan,Xin Bao,Yong-Zhong Du,Jian You,Fu-Qiang Hu

Implantable 3D Printed Hydrogel Scaffolds Loading Copper-Doxorubicin Complexes for Postoperative Chemo/Chemodynamic Therapy

Wentao Dang,Yuqin Wang,Wei-Chih Chen,Enguo Ju,Rachel L. Mintz,Yue Teng,Lili Zhu,Kun Wang,Shixian Lv,Hon Fai Chan,Yu Tao,Mingqiang Li

Biomaterial-based implants hold great potential for postoperative cancer treatment due to the enhanced drug dosage at the disease site and decreased systemic toxicity. However, the elaborate design of implants to avoid complicated chemical modification and burst release remains challenging. Herein, we report a three-dimensional (3D) printed hydrogel scaffold to enable sustained release of drugs for postoperative synergistic cancer therapy. The hydrogel scaffold is composed of Pluronic F127 and sodium alginate (SA) as well as doxorubicin (DOX) and copper ions (F127-SA/Cu-DOX hydrogel scaffold). Benefiting from the coordination of Cu(II) with both SA and DOX, burst release of DOX can be overcome, and prolonged release time can be achieved. The therapeutic efficiency can be adjusted by altering the amount of DOX and Cu(II) in the scaffolds. Moreover, apoptosis and ferroptosis of cancer cells can be induced through the combination of chemotherapy and chemodynamic therapy. In addition, DOX supplies excess hydrogen peroxide to enhance the efficiency of Cu-based chemodynamic therapy. When implanted in the resection site, hydrogel scaffolds effectively inhibit tumor growth. Overall, this study may offer a new strategy for fabricating local implants with synergistic therapeutic performance for preventing postoperative cancer recurrence.