Frontiers in Pharmacology
·
2019
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IF 3.845
Feng Chan,Zhu Donglei,Chen Lv,Lu Yonglin,Liu Jie,Kim Na Yoon,Liang Shujing,Zhang Xia,Lin Yun,Ma Yabin,Dong Chunyan
The off-target activation of photosensitizers is one of the most well-known obstacles to effective photodynamic therapy (PDT). The selected activation of photosensitizers in cancer cells is highly desired to overcome this problem. We developed a strategy that enabled diselenide bonds to link hyaluronic acid (HA) and photosensitizer chlorin e6 (Ce6) to assemble the micelles (HA-sese-Ce6 NPs) that can target cancer and achieve a redox responsive release of drugs to enhance the PDT efficiency in breast cancer. The HA was used to form a hydrophilic shell that can target cluster of differentiation 44 (CD44) on the cancer cells. The selenium-containing core is easily dissembled in a redox environment to release Ce6. The triggered release of Ce6 in a redox condition and the positive feedback release by activated Ce6 were observed in vitro. In cytotoxicity assays and in vitro cellular uptake assays, the increased PDT efficiency and targeted internalization of HA-sese-Ce6 NPs in the cells were verified, compared to a free Ce6 treated group. Similar results were showed in the therapeutic study and in vivo fluorescence imaging in an orthotopic mammary fat pad tumor model. In addition, a significant inhibition of metastasis was found after the HA-sese-Ce6 NPs treatment. In general, this study promises an ingenious and easy strategy for improved PDT efficiency.
研究领域:
癌症研究
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药学科学
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治疗学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2025
·
IF 5.7
Haizhou Qiu,Kunlin Chen,Yiwen Qiu,Yi Yang,Tao Wang,Li Jiang,Wentao Wang
Hepatocellular carcinoma (HCC) is a highly aggressive malignancy characterized by inadequate drug delivery to tumor sites, insufficient immune activation, and poor response to conventional monotherapies. To overcome these limitations, we developed a pH and near-infrared (NIR) responsive nanoplatform (DOX@MPDA-TPP@HA) by encapsulating doxorubicin (DOX) into mesoporous polydopamine (MPDA) nanoparticles functionalized with triphenylphosphonium (TPP) and hyaluronic acid (HA) to achieve mitochondrial and CD44 dual-targeting. This system enables combined chemotherapy and photothermal therapy, while simultaneously promoting immunogenic cell death and enhancing antitumor immunity. In vitro and in vivo experiments demonstrated that the nanoplatform exhibits acid and NIR-triggered drug release, efficient photothermal conversion, and enhanced cellular uptake in tumor cells. Treatment significantly increased calreticulin exposure and high-mobility group box 1 (HMGB1) release, both recognized as hallmarks of immunogenic cell death. Flow cytometry revealed a marked increase in the maturation of CD11c⁺CD80⁺CD86⁺ dendritic cells in tumor-draining lymph nodes, elevated intratumoral CD8⁺ cytotoxic T lymphocyte infiltration, and a reduction in CD4⁺Foxp3⁺ regulatory T cells. Enzyme-linked immunosorbent assay (ELISA) confirmed the elevated secretion of proinflammatory cytokines including interleukin-6, interleukin-12, tumor necrosis factor-alpha, and interferon-gamma, suggesting immune reprogramming of the tumor microenvironment.
研究领域:
纳米医学
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癌症治疗
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免疫治疗
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药物递送系统
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生物医学工程
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分子肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2017
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IF 4.811
Ting Zhao,Yue He,Huali Chen,Yan Bai,Wenjing Hu,Liangke Zhang
We aimed to construct a novel nano-assembly carrying apigenin (APG), a hydrophobic drug, and to evaluate its in vitro targeting ability for A549 cells overexpressing CD44 receptors. The apigenin-loaded sodium hyaluronate nano-assemblies (APG/SH-NAs) were assembled by multiple non-covalent interactions between sodium hyaluronate (SH) and APG. The prepared APG/SH-NAs exhibited a small average size and narrow particle size distribution. In addition, satisfactory encapsulation efficiency and drug loading were obtained. The drug release curves indicated that APG/SH-NAs achieved a sustainable drug-release effect due to the presence of hydrophilic materials. The in vitro cytotoxicity of APG/SH-NAs against A549 cells and HepG2 cells was evaluated, and the results indicated that the prepared APG/SH-NA showed higher cytotoxicity compared to apigenin suspensions. When CD44 receptors on the surface of A549 cells were blocked by the addition of excess SH, the cytotoxicity of APG/SH-NA was significantly reduced. However, similar phenomena were not observed in HepG2 cells with relatively low CD44 receptor expression. The resulting APG/SH-NAs could efficiently facilitate the internalization of APG into A549 cells, which might be due to their high affinity for CD44 receptors. Moreover, the apoptotic rate of APG/SH-NAs through receptor-mediated endocytosis mechanism was higher than that of the other groups in A549 cells. Thus, such nano-assemblies were considered to be an effective transport system with excellent affinity for CD44 receptors to allow the SH-mediated targeted delivery of APG.
研究领域:
药剂学
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肿瘤学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2026
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IF 5.2
Dandan Liu,Changwei An,Danfeng Zhang,Yujia Qi,Hao Pan
HA@PDA/Cu/DOX oral nanoplatform is designed for CRC synergistic CT/CDT therapy. • The nanosystem shows efficient DOX loading and sustained release to avoid premature leakage. • HA modification enhances the nanoplatform's mucus penetration ability. • The nanoplatform achieves CD44-mediated uptake and CT/CDT synergy against CT26 cells. • HA@PDA/Cu/DOX realizes deep intratumoral penetration in 3D colon tumor spheroids. Clinical outcomes in colorectal cancer (CRC) are frequently compromised by systemic toxicity and poor tumor targeting associated with conventional chemotherapy (CT) regimens. Herein, we rationally designed an oral colon-targeted nanoplatform, HA@PDA/Cu/DOX, for synergistic CT and chemodynamic therapy (CDT) to address these limitations. The system consists of a polydopamine (PDA) core that co-delivers doxorubicin (DOX) and copper ions, surface-functionalized with hyaluronic acid (HA) for CD44-mediated active targeting. Physicochemical characterization verified the successful preparation of the formulation, with DOX loading efficiency of 5.64 ± 0.42%, and a uniform size distribution. In vitro investigations showed that HA@PDA/Cu/DOX achieved sustained drug release, and displayed favorable mucus penetration (67.81%). HA-mediated targeting was observed to promote cellular uptake in CT26 cells, mainly through clathrin- and lipid raft/caveolae-dependent endocytosis. Meanwhile, Cu 2+ -catalyzed Fenton-like reactions were shown to generate reactive oxygen species (ROS) and deplete glutathione (GSH), thereby disturbing redox balance and sensitizing tumor cells to DOX. In addition, the nanosystem enabled deep penetration into 3D tumor spheroids (up to 72 μm) and exhibited cytotoxic effects, with CT26 cell viability below 15% at a DOX concentration of 5 μg/mL. This fabricated oral system combines colon-targeted delivery with gastrointestinal barrier penetration and synergistic CT/CDT therapy, exhibiting excellent in vitro antitumor performance and providing a feasible basis for subsequent in vivo verification and CRC treatment research. Download: Download high-res image (350KB) Download: Download full-size image
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DOI
高影响因子
Advanced Science
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2026
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IF 14.1
Yao Xiao,Yuxuan Yang,Haosen Qiu,Jia Yang,Hao Liang,Zhaojun Jiang,Xiao Tong,Yongying Li,Qunfeng Huang,Jiaming Wu,Tian Lin,Jiang Yu,Min Liang
Colorectal cancer (CRC) remains therapeutically challenging due to high metastasis, recurrence, and immunotherapy resistance driven by tumor microenvironment-mediated immune evasion. Immunogenic cell death (ICD) offers a promising strategy to reshape the immune microenvironment, yet existing ICD inducers suffer from poor targeting efficiency and insufficient death signal release. Here, we constructed a calcium overload-based smart nanosystem, HA-HAP@CUR, to achieve highly efficient ICD induction via a triple-effect mechanism: hyaluronic acid (HA)-mediated CD44 targeting enables tumor-selective accumulation; pH-responsive hydroxyapatite (HAP) degradation releases Ca 2+ in the acidic tumor microenvironment; and curcumin (CUR) amplifies intracellular calcium overload by promoting endoplasmic reticulum Ca 2+ release, collectively establishing a positive feedback loop disrupting calcium homeostasis. Mechanistically, calcium overload induces mitochondrial membrane potential dissipation and sustained mPTP opening, triggering mitochondrial oxidative stress and energy metabolic disorders. This mitochondrial crisis concurrently activates caspase-3, GSDMD, and RIPK1, synergistically initiating apoptosis, pyroptosis, and necroptosis, ultimately converging into PANoptosis with potent immunostimulatory potential. This strategy, encompassing targeted accumulation, calcium storm activation, and multi-modal cell death synergy, provides a biologically precise approach to overcoming immunotherapy resistance in CRC.
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2016
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IF 3.902
Jing Zhang,Yujie Sun,Baocheng Tian,Keke Li,Lele Wang,Yan Liang,Jingtian Han
In this paper, a CD44-targeted and redox-responsive drug delivery system based on mesoporous silica nanoparticles (MSNs) was synthesized by conjugating tumor-shedable hyaluronic acid (HA) on the surface of MSNs via disulfide bonds. Doxorubicin hydrochloride (DOX·HCl) was physically encapsulated into HA modified MSNs (MSNs/SS/HA@DOX) as a model drug. MSNs/SS/HA@DOX (40 nm) had a high drug loading (14.1%) and redox-responsive drug release property. The cellular uptake behaviors of MSNs/SS/HA@DOX by HeLa and LO2 cells were evaluated by confocal laser scanning microscopy (CLSM) and flow cytometry (FCM). MSNs/SS/HA@DOX exhibited higher cellular uptake efficacy via CD44-mediated endocytosis by HeLa cells (CD44 over-expressed cells) than by LO2 cells (CD44 deficient cells). The in vitro cytotoxicity assay demonstrated that MSNs/SS/HA@DOX exhibited higher cytotoxicity to HeLa cells than to LO2 cells. These results indicated that MSNs/SS/HA@DOX might be promising as a multifunctional drug delivery system to improve the anti-tumor efficacy of chemotherapeutic drugs.
研究领域:
药剂学
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肿瘤学
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
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2022
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IF 8.101
Jin Li,Zi-Hui Wang,Ya-Min Dang,Dan-Ni Li,Zhen Liu,Da-Peng Dai,Jian-Ping Cai
MTH1 protein can sanitize the damaged (d)NTP pool and MTH1 inhibitors have been developed to impede the growth of rapidly proliferating tumor cells; however, the effect of MTH1 inhibition on breast cancer stemness has not been reported yet. Here, we constructed breast cancer cell lines with the stable depletion of MTH1. MTH1 suppression clearly increased the ratio of CD44 + CD24 −/low subpopulations and promoted the formation of tumorspheres in MCF7 and T47D cells. RNA expression profiling, RT–qPCR and Western blotting showed the upregulation of master stem cell transcription factors Sox2 , Oct4 and Nanog in MTH1 knockdown cells. GSEA suggested and Western blotting verified that MTH1 knockdown increased the expression of phosphorylated STAT3 (Tyr705). Furthermore, we indirectly demonstrated that the increased concentration of 8-oxo-dGTP and 8-oxo-GTP in MTH1 -knockdown cells and exogenous 8-oxoGTP, rather than 8-oxo-dGTP, could significantly increase the phosphorylation of STAT3. In conclusion, this work indicates that MTH1 inhibition increased the proportion of breast cancer stem cells (BCSCs) and promoted stemness properties in MCF7 cells.
研究领域:
肿瘤学
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分子生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2024
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IF 10.7
Pengrong Zhu,Lingtong Meng,Yue Shu,Yuqiao Xu,Weiming Liu,Yong Bi,Jian Xu,Lijuan Meng,Yanan Li
The abundance of Fusobacterium nucleatum ( F. nucleatum ) is highly associated with the development and poor prognosis of colorectal cancer (CRC), which is regarded as a promising target for CRC. However, until now, the novel strategy to clear F. nucleatum in the colon and CRC has not been well proposed. Herein, a probiotic strain Enterococcus faecium ( E. faecium , EF47) is verified to secrete various organic acids and bacteriocins to exert superior antimicrobial activity towards F. nucleatum . However, the oral delivery of EF47 is affected by the complex digestive tract environment, so we design the hyaluronic acid-inulin (HA-IN) coated EF47 for colon-targeted delivery to fight F. nucleatum . IN can protect EF47 from the harsh gastrointestinal tract environment and is degraded specifically in the colon, acting as prebiotics to further promote the proliferation of EF47. The exposed HA can also enhance the targeting effect to the tumor area via the interaction with the CD44 receptor on the tumor cells, which is confirmed to increase the adhesive ability in tumor tissues and inhibit the growth of F. nucleatum . Therefore, this colon-targeted delivery system provides a novel platform to realize high-activity and adhesive delivery of probiotics to assist the therapeutic efficiency of CRC.
研究领域:
微生物学
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药学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
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IF 8.3
Songtao Li,Tianxing Lv,Xiaxia Fan,Mangmang Feng,Meng Zhou,Zhuoyu Li
Background Chemotherapy remains the main treatment for colon cancer, but the development of resistance has limited its efficacy. There is an urgent need to exploit a more effective therapeutic strategy. Alpha-linolenic acid (ALA), as an essential nutrient for the human body, has been found to increase the therapeutic effect of chemotherapy drugs. Purpose Exploring the potential mechanism of alpha linolenic acid reversing chemotherapy resistance in colon cancer. Results ALA reverses chemoresistance in colorectal cancer and suppresses stemness in resistant colorectal cancer cells. SPP1 functions as a key mediator in ALA-induced reversal of chemoresistance; its downregulation disrupts the interaction with the downstream receptor CD44, thereby mitigating chemotherapy resistance. Subsequently, ALA inhibits the expression of SOX2, a transcription factor that promotes SPP1 transcription. Further analysis revealed that decreased SPP1 expression leads to reduced levels of FAP, a marker of cancer-associated fibroblasts (CAFs), and that a functional interaction exists between SPP1 and FAP. Interestingly, ALA disrupted the interaction between SPP1 and FAP, thereby preventing CAFs accumulation. In vivo studies confirmed that ALA reverses colorectal cancer chemoresistance via the SOX2/SPP1/FAP signaling axis. Conclusion The study demonstrates that ALA in quinoa depresses the stemness of colorectal cancer and reduces the number of CAFs via SPP1, thereby reversing chemotherapy resistance. These findings highlight ALA as a promising dietary-based adjuvant for enhancing chemotherapy efficacy in colorectal cancer and provide new mechanistic insights into targeting tumor stemness and stromal remodeling.
研究领域:
肿瘤学
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分子生物学
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营养与癌症
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转化医学
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肿瘤微环境
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干细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2018
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IF 8.097
Yao-Hui Zhang,Wen-Xiu Qiu,Mingkang Zhang,Lu Zhang,Xian-Zheng Zhang
Here, a tumor-targeted MnO2 motor nanosystem (designed as MG/HA) was constructed by the assembly of glucose oxidase (GOD), manganese dioxide (MnO2), and glycoprotein CD44-targeting polymer hyaluronic acid (HA) to elevate cancer-starving therapy efficacy in solid tumor. Upon the specific uptake of MG/HA by CD44 overexpressed cancer cells, GOD catalyzed the oxidation of glucose into gluconic acid and hydrogen peroxide (H2O2) accompanying the consumption of oxygen (O2). Meanwhile, MnO2 would react with H2O2 and acid to generate O2, which is in turn supplied to the glucose-depletion process, running like a loop. As a result, MnO2 is displayed as a motor to promote the rate of glucose depletion that contributed to the starving therapy. In contrast to G/HA, MG/HA could not only achieve effective glucose consumption to depress cancer progression, but also alleviate hypoxia and reduce the expression of Glut1 to inhibit the metabolism for further restraining the tumor aggressiveness and metastasis. The concept of MnO2 motor shows a promising prospect to overcome the restriction of the starving therapy.
研究领域:
肿瘤学
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生物医学工程
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药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2026
·
IF 8.2
Shaoyou Wang,Quan Zhou,Jiachen Hong,Xinrong Wang,Baocai Zhang,Huihui Wang,Yong Shi,Ayesha Younas,Shuanghu Wang,Shujiao Lu
A CD44-targeted, NIR-II-responsive nanoplatform (CuS@ZIF-8/HA NPs) was developed for TNBC therapy. • Acidic TME triggers ZIF-8 decomposition, releasing Cu 2+ for sustained mitochondrial copper overload. • Cu + drives lipoylated DLAT oligomerization, the core event of cuproptosis. • NIR-II photothermal therapy (55.6 °C) synergizes with cuproptosis for enhanced tumor ablation. • In vivo : pronounced tumor suppression without relapse or toxicity. Triple-negative breast cancer (TNBC) lacks targetable receptors and rapidly expels cytotoxic copper via ATPase copper–transporting alpha/beta (ATP7A/B) pumps, rendering conventional cuproptosis inducers ineffective. We report an acid-activatable, CD44-directed nanoplatform (CuS@ZIF-8/HA NPs) that converts NIR-II irradiation into a synchronized mitochondrial “copper flood–heat shock” event. In the acidic tumor microenvironment, ZIF-8 decomposes and releases Cu 2+ , which is reduced to cytotoxic Cu + , triggering oligomerization of lipoylated dihydrolipoamide S-acetyltransferase (DLAT), the core driver of cuproptosis. Concomitant ferredoxin 1 (FDX1) protein degradation serves as a downstream biochemical marker of cuproptotic injury. The photothermal effect (55.6 °C at 1 W cm −2 ) simultaneously accelerates copper release, amplifies oxidative damage, and ablates cells by hyperthermia. In 4 T1 tumor mice model, eight i.v. doses (10 mg kg −1 ) plus NIR-II light achieved profound tumor suppression without relapse or systemic toxicity, outperforming either monotherapy. Thus, CuS@ZIF-8/HA NPs turns NIR-II light into a spatially confined cuproptotic-photothermal double hit, offering a safe, precise, and translatable strategy against therapy-refractory TNBC. Download: Download high-res image (174KB) Download: Download full-size image
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DOI
高影响因子
ACS Applied Nano Materials
·
2025
·
IF 5.5
Hongyan Liu,Jie Shi,Jiafan Bai,Wenzhen Peng,Jie Weng,Wei Zhi,Jianxin Wang,Min Jia
Gastric ulcers, caused by factors such as H. pylori infection and NSAID misuse, are characterized by mucosal barrier erosion and severe complications. Current therapeutic approaches employing proton pump inhibitors, H2-receptor antagonists, antibiotics, and antacids face challenges, including reduced bone density, rising antibiotic resistance, and poor drug targeting. Here, we developed a dual-targeting oral nanodelivery system (CFLTM) with a size range of 100 nm to 450 nm and an average size of 335 nm using a cascade-targeting strategy. CFLTM combines folic acid and chondroitin sulfate to enhance targeting precision in an acidic gastric environment. It is loaded with tannic acid and magnolol for anti-inflammatory and antioxidant effects. The study shows that CFLTM exhibits exceptional targeting efficiency, with its dual-targeting uptake capability demonstrating a significant 1.21-fold enhancement compared to single-targeting systems. This enables rapid and precise localization to gastric ulcer sites while reducing oxidative stress and inflammation through modulation of key biomarkers. Using a green aqueous synthesis process, CFLTM achieves low energy consumption and high encapsulation efficiency. This innovative system shifts gastric ulcer treatment from passive acid suppression to active tissue repair, providing a new therapeutic approach and a platform for treating other digestive diseases.
研究领域:
纳米医学
·
胃肠病学
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药物递送
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生物材料
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炎症性疾病
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抗氧化治疗
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靶向治疗
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）