Advanced Therapeutics
·
2023
·Vol. 6
·期 4
·2200304
·
IF 4.6
Dan Zhao,Min Wu,Yanan Tian,Lu Gao,Fu Wang
With the advantages of ferroptosis therapy (FT) in solving the apoptotic resistance of tumors, a smart strategy based on the combination of glucose oxidase (GOx) and ferroptosis-inducing nanoagents is proposed to boost the FT. However, most of the nanoagents remain limited in complex synthesis, poor targeting specificity, and unclarified biological mechanisms. Herein, a multifunctional nanoplatform based on fluorescent apoferritin-gold nanoclusters combined with GOx (AFt-AuNCs@GOx) is designed for tumor-targeted imaging and FT. The results show that AFt-AuNCs@GOx catalyze the generation of toxic ·OH from H 2 O 2 supplied by GOx. Consequently, AFt-AuNCs@GOx induce the enhanced ferroptosis effect in 4T1 cells. Additionally, the transcriptome assay of 4T1 cells identifies the differential expression genes related to ferroptosis process after AFt-AuNCs@GOx treatment. Moreover, with the merit of intrinsic fluorescence, the biodistribution both in vitro and in vivo of AFt-AuNCs@GOx can be effectively visualized. In vivo evidences reveal that AFt-AuNCs@GOx have the desired efficacy of FT and excellent biosafety. Overall, the AFt-AuNCs@GOx nanoplatform offer remarkable advantages in simple architecture, fluorescent imaging, precise targeting, and tumor inhibition. The exploration of the ferroptosis effect and biological mechanisms of AFt-AuNCs@GOx, as well as its application in tumor therapy, can introduce a new insight into the field of ferroptotic nanomedicine.
研究领域:
纳米技术
·
癌症治疗
·
分子生物学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2025
·
IF 4.5
Shuang Yang,Beibei He,Cuiping He,Fengye Zhao,Ran Li,Minfei Shi,Bin Zheng
As a potential drug, antisense oligonucleotides (AO) have considerable application prospects in the field of tumor treatment. However, the main problem to be solved is the lack of an efficient and safe carrier that contributes to reaching the target cancer cells and utilizing the antitumor effect of AO. Here, we designed and developed a novel AO delivery system, which was based on a modified polyethylenimine (PEI) named TPGS-SS-PEI by connecting tocopherol polyethylene glycol succinate (TPGS) to PEI through the disulfide bond (SS) and the biomimetic red blood cell membrane vesicles (RVs). R-TSP/AO was composed of an AO-loaded micelle (TSP/AO) as the “core” prepared by TPGS-SS-PEI, and RVs as the “shell”. The formulations and properties of R-TSP/AO were optimized and characterized. The mean particle size and zeta potential of R-TSP/AO were 109.7 nm and −24.10 mV, respectively. In vitro studies indicated that R-TSP/AO was sensitive to highly reducing conditions and exhibited excellent stability and high security. In addition, R-TSP showed higher AO transfection efficiency and excellent gene silencing efficiency compared with unmodified PEI (P < 0.001). R-TSP/AO exhibited potent tumor inhibition (55.65%) in 4T1 tumor-bearing mice without inducing systemic toxicity. These findings suggested that R-TSP/AO was safe and efficient in enhancing the antitumor efficacy and R-TSP had the potential to be further researched as a carrier for nucleic acid drugs delivery.
研究领域:
药剂学
·
纳米技术
·
分子治疗学
·
生物医学工程
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Sustainable Chemistry & Engineering
·
2021
·
IF 8.198
Yong-E Gao,Shengxin Hou,Jiaqi Cheng,Xinyi Li,Yongqiong Wu,Yuran Tang,Yanke Li,Peng Xue,Yuejun Kang,Zhigang Xu,Mingming Guo
With the merits of noninvasiveness, flexibility of treatment, and nonsystemic toxicity, photodynamic therapy (PDT) holds great promise in fighting against malignant cancers. Issues with conventional PDT, including severe hydrophobicity of the majority of photosensitizers (PSs), poor accumulation at the tumor site, and potential long-term side effects, greatly attenuate its therapeutic efficacy. Nanotheranostic systems are thus expected to assist our battle against cancer. Herein, we rationally designed the silk sericin (SS) based nanoparticles (designated as SSC NPs), in which photosensitizer chlorin e6 (Ce6) was conjugated with water-soluble SS via simple amidation reaction, for enhanced imaging-guided PDT. Compared with free Ce6, the as-prepared SSC NPs showed enhanced intracellular uptake efficiency and penetrability into tumor spheres. Furthermore, the SSC NPs exhibited negligible cytotoxicity toward 4T1 cells in darkness, while presenting a remarkable anticancer effect under a reduced laser power density (660 nm, 100 mW cm−2), indicating their good biocompatibility and feasibility as PDT nanoagents. Following systemic administration in 4T1 tumor-bearing mice, the SSC NPs achieved superior accumulation in tumor sites in comparison with free Ce6, which might contribute to prolonged blood circulation of nanoscale drugs. In vivo studies revealed that SSC NPs suppress the growth of tumors more effectively compared to free Ce6 and did not induce apparent side effects to the treated animals. Taken together, these results indicate that the SSC NPs have an exciting opportunity as an alternative candidate for SS-based phototherapy of cancer.
研究领域:
纳米技术
·
癌症研究
·
治疗诊断学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2018
·
IF 8.097
Zhanwei Zhou,Chenzi Li,Minghua Zhang,Qingyan Zhang,Chenggen Qian,David Oupicky,Minjie Sun
Hydrophobic modification on polycations were commonly used to improve the stability and transfection efficiency of polyplexes. However, the improved stability often means undesired release of the encapsulated siRNA, limiting the application of cationic micelles for siRNA delivery. The current strategy of preparing bioresponsive micelles based on the cleavage of sensitive linkages between polycation and hydrophobic part was far from sufficient, owing to the siRNA binding of the separated polycations from micelles leading to the incomplete release of siRNA. In this study, we propose a new strategy by the combination of micelles disassembly and separated polycations charge reversal. FPBA (3-fluoro-4-carboxyphenylboronic acid) grafted PEI 1.8 k (polyethylenimine) as the polycations of PEI-FPBA and dopamine (with diol-containing moiety) conjugated with cholesterol as the hydrophobic part (Chol-Dopa). The PFCDM micelles was assembled by PEI-FPBA and Chol-Dopa, based on the FPBA-Dopa conjugation. The prepared PFCDM showed strong siRNA loading ability and superior stability in the presence of PBS or serum. Besides, the PFCDM exhibited excellent ATP sensibility. The intracellular ATP could effectively trigger the disassembly of micelles and charge reversal of PEI-FPBA, resulting in the burst release of siRNA in the cytosol. With the property of extracellular stability and intracellular instability, PFCDM displayed good performance on in vitro and in vivo luciferase silencing on 4T1 cells. It should also be noted that the assembly of low molecular weight PEI was relatively safe to cells compared with 25 k PEI. To sum up, the ATP-fueled assembly and charge reversible micelles gave examples for polyplexes to achieve better stability and on demand cargo release at the same time and shows potential to be used for in vitro and in vivo siRNA transfection.
研究领域:
纳米技术
·
药学
·
生物医学工程
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2023
·
IF 14
Zhuoya Gao,Jiarong Zhang,Yingchao Hou,Jinjin Lu,Jing Liang,Yufeng Gao,Boqi Li,Shuai Gao,Yanjun Zhao,Min Gao,Jinghua Chen
Both ferroptotic therapy and immunotherapy have been widely employed in cancer treatment. However, ferroptotic cell death fails to induce dendritic cells maturation, which limits the therapeutic outcome of ferroptotic cancer therapy. To address this, the current work reports a tailored liposome to establish a positive loop between ferroptotic therapy and immunotherapy. As the key component of liposome, a unique phospholipid is designed to bear two arachidonic acid tails. The liposome is further surface-engineered with fucose ligand and physically encapsulates immunostimulatory CpG oligodeoxynucleotides (ODNs). The tailored liposome shows enhanced cellular uptake in a model 4T1 cell line. Meanwhile, the high level of reactive oxygen species in cancer cells can induce ferroptosis-specific peroxidation of DAPC and trigger the release CpG ODNs. The CpG ODNs further enable the maturation of dendritic cells and enhance the effector function of CD8 + T cells . IFN-γ released from CD8 + T cells promotes cancer cell ferroptosis via inhibiting SLC7A11 and suppressing the biosynthesis of glutathione . The tailored liposome can also act in synergism with PD-L1 antibody, resulting in enhanced anti-cancer efficacy in a 4T1 tumor-bearing mice model. This work provides a promising strategy for cancer treatment through orchestrating ferroptotic therapy and immunotherapy.
研究领域:
肿瘤学
·
药学
·
免疫学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMISTRY OF MATERIALS
·
2024
·
IF 7.2
Xiangjie Tian,Hui Xu,FangFang Zhou,Xiyu Gong,Songwen Tan,Yongju He
Cuproptosis is a newly identified copper-dependent cell death and holds great promise for cancer therapy. However, transporting enough copper into cancer cells is a challenge. Herein, an intelligent cupreous nanoplatform (denoted as CuO2-MSN@TA-Cu2+), consisting of in situ formation of CuO2 within mesoporous silica nanoparticles (MSN) and then deposition with a tannic acid (TA)-Cu2+ complex, is designed and developed to realize on-demand copper delivery for cuproptosis-based combination therapy. CuO2-MSN@TA-Cu2+ exhibits tumor microenvironment-triggered therapeutic activity, wherein the outer TA-Cu2+ complex is readily disassembled to release Cu2+ and liberate the internal CuO2 to produce Cu2+ and H2O2. The overloaded Cu2+ can not only directly convert endogenous H2O2 and self-supplied H2O2 into highly toxic hydroxyl radicals for chemodynamic therapy (CDT) via Cu-based Fenton-like reaction but also undergo glutathione-mediated reduction into Cu+ species to induce potent cellular cuproptosis and enhance CDT. The experimental results indicate that CuO2-MSN@TA-Cu2+ produces remarkable cytotoxicity against cancer cells and significantly suppresses tumor growth by 93.42% in mice-bearing 4T1 breast tumors. This work provides a new paradigm to boost cuproptosis-related therapy and may also inspire the design of advanced therapeutic nanoplatforms.
研究领域:
纳米技术
·
癌症生物学
·
治疗学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2020
·
IF 10.652
Dejun She,Shaojun Peng,Li Liu,Huihui Huang,Yingyan Zheng,Yiping Lu,Daoying Geng,Bo Yin
Hypothermal photothermal therapy (HPTT) employs hyperthermia (<45 °C) to destroy tumor cells with negligible side effects to the surrounding normal tissues. Despite extensive studies, the clinical translation of HPTT is severely hindered, owing to the discounted therapeutic effect and maximum permissible power of near-infrared (NIR) laser by food and drug administration (FDA). Herein, we report a rational design of red blood cell membranes (RBCs) coated FeS 2 (FeS 2 @RBCs) with strong absorption at NIR-Ⅱ window for effective HPTT augmented chemodynamic therapy (CDT). FeS 2 @RBCs exhibits prolonged blood circulation and negligible immune response, leading to improved tumor accumulation for enhanced HPTT. Furthermore, the CDT effect of FeS 2 @RBCs is significantly augmented by the temperature elevation in the tumor region, which leads to the synergetic HPTT and CDT. Lipidomics analysis reveals that the damage of tumor cells by CDT is via the lipid peroxidation. In addition, FeS 2 @RBCs exhibits self-enhanced magnetic resonance imaging after reacting with H 2 O 2 in tumor region for imaging-guided laser irradiation. Thus, FeS 2 @RBCs achieves remarkable inhibition of subcutaneous 4T1 breast tumor growth without obvious side effects by a 1064 nm laser irradiation of 1.0 W/cm 2 (FDA approved power density). Overall, this work provides a HPTT augmented CDT strategy for effective cancer therapy with a clinical approved laser power, which may pave the way for the clinical application of HPTT augmented CDT in the future.
研究领域:
癌症治疗
·
生物医学工程
·
纳米技术
·
分子生物学
·
药学
✓ 已验证
产品关联
DOI
高影响因子
ACS Nano
·
2020
·
IF 14.588
Xuliang Guo,Fang Liu,Jian Deng,Peipei Dai,Yan Qin,Zhi Li,Bingbing Wang,Aiping Fan,Zheng Wang,Yanjun Zhao
Ferroptotic antitumor therapy has been compromised by various intracellular antioxidants, particularly glutathione and thioredoxin. Both are cofactors of glutathione peroxide 4 (GPX4) that act against oxidative stress via catalyzing the reduction of lipid peroxides. It was postulated that tailored polymer micelles could enhance ferroptotic antitumor efficacy via diminishing glutathione and thioredoxin under hypoxia. The aim was to engineer hypoxia-responsive micelles for selective enhancement of ferroptotic cell death in solid tumor. The polymer contains hydrophilic poly(ethylene glycol) (PEG) that is linked by azobenzene linker with nitroimidazole-conjugated polypeptide. The tailored polymer could self-assemble into nanoscale micelles to encapsulate RAS-selective lethal small molecule 3, a covalent GPX4 inhibitor. Under hypoxia, the azobenzene moiety enabled PEG shedding and enhanced micelles uptake in 4T1 cells. Likewise, the nitroimidazole moiety was reduced by the overexpressed nitroreductase with reduced nicotinamide adenine dinucleotide phosphate (NADPH) as the cofactor, resulting in transient depletion of NADPH. This impaired both the glutathione and thioredoxin redox cycle, leading to diminished intracellular glutathione and thioredoxin. The selective potency of ferroptotic micelles in depleting NADPH, glutathione and thioredoxin was further verified in vivo in the 4T1 tumor xenograft mice model. This work highlights the role of hypoxia-responsive polymers in enhancing the potency of ferroptotic inducers against solid tumors without additional side effects to healthy organs.
研究领域:
肿瘤学
·
药学
·
生物医学工程
·
癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2024
·
IF 5.3
Ge Sun,Yubiao Huang,Xiaoyu Cheng,Lijun Fang,Chunling Wang,Yinlong Zhang
Anlotinib, a multitargeted tyrosine kinase inhibitor (TKI) with a dual effect of inhibiting both tumor angiogenesis and tumor cell proliferation, holds great promise in cancer therapy. However, its clinical application has been limited due to off-target side effects. With the rapid development of drug delivery systems, there is increasing potential to improve therapeutic efficacy while reducing the toxicity associated with free drugs. Among these, liposomes stand out due to their excellent biocompatibility, and several liposomal drug formulations have been approved by the U.S. Food and Drug Administration (FDA). In this study, we prepared anlotinib-loaded liposomes (designated as Lipo-Anlotinib) using the ammonium sulfate gradient method, aiming to enhance its clinical applicability through a more efficient delivery system. The antitumor activity of Lipo-Anlotinib was evaluated in vitro against three cell lines (A549, 4T1, and CT26). Additionally, Lipo-Anlotinib exhibited improved therapeutic efficacy over free anlotinib in a 4T1 subcutaneous tumor model. Serum biochemical analysis and histological examination revealed that Lipo-Anlotinib exhibited reduced toxicity in comparison to free anlotinib. This liposomal formulation offers a promising approach to enhancing the antitumor efficacy while mitigating the side effects of anlotinib.
研究领域:
药理学
·
肿瘤学
·
纳米技术
·
生物医学工程
·
癌症治疗
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Kexin Fan,Ludan Zhang,Qinqiu Zhong,Yanhe Xiang,Bowei Xu,Yuguang Wang
Although acceptor-donor-acceptor (A-D-A)-type molecules show advantages in constructing NIR absorbing photothermal agents (PTAs) due to their strong intramolecular charge transfer and molecular planarity, their applications in photothermal therapy (PTT) of tumor are insufficiently explored. In particular, the influence of ESP distribution on optical properties of A-D-A photosensitizers has not been investigated. Herein, we utilized the advantages of A-D-A-type molecules with large ESP difference to construct NIR absorbing PTA with sufficient extinction coefficient (ɛ) and high photothermal conversion efficiency (PCE). The calculation results of density functional theory (DFT) indicate that the large ESP difference of Y6 may increase intermolecular interactions and induce tight packing of the A-D-A photosensitizer. As a result, Y6 NP exhibited an obvious bathochromic shift of absorption peak from 711 nm to 822 nm, with a NIR-II emission extended to 1400 nm. Moreover, a sufficient ɛ of 3.34 L·g-1·cm-1 and PCE of 66.3% were attained, making Y6 NP suitable for PTT. With a concentration of 100 μg/mL, Y6 NPs in aqueous dispersion yielded a death rate of 93.4% for 4T1 cells upon an 808 nm laser irradiation (1 W·cm-2) for 10 min, which is comparable with the best results of recently reported PTT agents.
研究领域:
生物医学工程
·
纳米技术
·
光疗
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Extracellular Vesicles
·
2023
·Vol. 12
·期 9
·12356
·
IF 16
Chuqi Liu,Dexiang Liu,Shen Wang,Lu Gan,Xiangliang Yang,Cong Ma
Exosomes play crucial roles in local and distant cellular communication and are involved in various physiological and pathological processes. Tumour-derived exosomes are pivotal to tumorigenesis, but the precise mechanisms underlying their secretion remain elusive. In particular, the SNARE proteins that mediate the fusion of multivesicular bodies (MVBs) with the plasma membrane (PM) in tumour cells are subject to debate. In this study, we identified syntaxin-4, SNAP-23, and VAMP-7 as the SNAREs responsible for exosome secretion in MCF-7 breast cancer cells and found that a SNARE complex consisting of these SNAREs can drive membrane fusion in vitro. Deletion of any of these SNAREs in MCF-7 cells did not affect MVB biogenesis and transportation, indicating their specific involvement in MVB–PM fusion. In addition, syntaxin-4, SNAP-23, and VAMP-7 play equivalent roles in exosome secretion in both HeLa cervical cancer cells and A375 melanoma cells, suggesting their conserved function in exosome secretion. Furthermore, deletion of VAMP-7 in 4T1 mammary carcinoma cells efficiently inhibited exosome secretion and led to significant attenuation of tumour growth and lung metastasis in mouse models, implying that VAMP-7 may hold promise as a novel therapeutic target for breast cancer.
研究领域:
癌症生物学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
INORGANIC CHEMISTRY
·
2025
·
IF 4.7
Zitian Zhuang,Yutong Gu,Wenjie Yang,Xianying Cao,Ling Zhang,Ke Jiang
Combination chemotherapy is a key strategy for improving cancer treatment efficacy and overcoming drug resistance, but it requires smart nanocarriers capable of codelivering multiple drugs and achieving precise release at the tumor site. Herein, we report a ZIF-90-based dual-drug delivery platform (NAR@ZIF-90-DOX) for synergistic cancer therapy. The natural product naringenin (NAR) was encapsulated within ZIF-90 pores via a “one-pot” method, while the chemotherapeutic drug doxorubicin (DOX) was covalently grafted onto the surface through a pH-sensitive Schiff base linkage. This dual-gated design leverages the acidic tumor microenvironment to trigger simultaneous ZIF-90 degradation and Schiff base cleavage. This enables the synchronous and targeted release of both drugs in 4T1 cells, leading to a significantly enhanced synergistic anticancer effect compared to single-drug administration. This work provides a strategy for designing multifunctional, intelligent Metal–Organic Frameworks (MOFs) nanoplatforms for combination chemotherapy.
研究领域:
纳米技术
·
药学
·
材料科学
·
生物化学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）