Advanced Healthcare Materials
·
2024
·
IF 10
Hao Fang,Tingting Wang,Jun Dai,Jing-Jing Hu,Zhaojun Chen,Lizhen Yuan,Yuning Hong,Fan Xia,Xiaoding Lou
Many diseases are associated with genetic mutation and expression of mutated proteins, such as cancers. Therapeutic approaches that selectively target the synthesis process of multiple proteins show greater potential compared to single-protein approaches in oncological diseases. However, conventional agents to regulate the synthesis of multiple protein still suffer from poor spatiotemporal selectivity and stability. Here, a new method using a dye-peptide conjugate, PRFK, for multi-protein interference with spatiotemporal selectivity and reliable stability, is reported. By using the peptide sequence that targets tumor cells, PRFK can be efficiently taken up, followed by specific binding to the KDELR (KDEL receptor) protein located in the endoplasmic reticulum (ER). The dye generates 1 O 2 under light irradiation, enabling photodynamic therapy. This process converts the furan group into a cytidine-reactive intermediate, which covalently binds to mRNA, thereby blocking protein synthesis. Upon treating 4T1 cells, the proteomics data show alterations in apoptosis, ferroptosis, proliferation, migration, invasion, and immune infiltration, suggesting that multi-protein interference leads to the disruption of cellular physiological activities, ultimately achieving tumor treatment. This study presents a multi-protein interference probe with the potential for protein interference within various subcellular organelles in the future.
研究领域:
癌症生物学
·
分子生物学
·
治疗学
·
光动力疗法
·
蛋白质组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2018
·
IF 3.095
Xiaoye Yang,Xiaoqun Shi,Jianbo Ji,Guangxi Zhai
The development of imaging-guided smart drug delivery systems for combinational photodynamic/chemotherapy of the tumor has become highly demanded in oncology. Herein, redox-responsive theranostic polymeric nanoparticles (NPs) were fabricated innovatively using low molecular weight heparin (LWMH) as the backbone. Chlorin e6 (Ce6) and alpha-tocopherol succinate (TOS) were conjugated to LMWH via cystamine as the redox-sensitive linker, forming amphiphilic Ce6-LMWH-TOS (CHT) polymer, which could self-assemble into NPs in water and encapsulate paclitaxel (PTX) inside the inner core (PTX/CHT NPs). The enhanced near-infrared (NIR) fluorescence intensity and reactive oxygen species (ROS) generation of Ce6 were observed in a reductive environment, suggesting the cystamine-switched “ON/OFF” of Ce6. Also, the in vitro release of PTX exhibited a redox-triggered profile. MCF-7 cells showed a dramatically higher uptake of Ce6 delivered by CHT NPs compared with free Ce6. The improved therapeutic effect of PTX/CHT NPs compared with mono-photodynamic or mono-chemotherapy was observed in vitro via MTT and apoptosis assays. Also, the PTX/CHT NPs exhibited a significantly better in anti-tumor efficiency upon NIR irradiation according to the results of in vivo combination therapy conducted on 4T1-tumor-bearing mice. The in vivo NIR fluorescence capacity of CHT NPs was also evaluated in tumor-bearing nude mice, implying that the CHT NPs could enhance the accumulation and retention of Ce6 in tumor foci compared with free Ce6. Interestingly, the anti-metastasis activity of CHT NPs was observed against MCF-7 cells by a wound healing assay, which was comparable to LMWH, suggesting LMWH was promising for construction of nanocarriers for cancer management.
研究领域:
肿瘤学
·
纳米技术
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2021
·
IF 5.875
Wei He,Yawei Du,Tao Wang,Ji Wang,Lei Cheng,Xinsong Li
7-Ethyl-10-hydroxycamptothecin (SN38), a potent camptothecin derivative specifically targeting DNA topoisomerase I cleavage complexes, has shown great potential in the treatment of solid tumors . Because of its poor solubility and chemical and metabolic stability, the clinical application of SN38 is highly limited. To address these problems, a novel redox-responsive SN38 conjugate based liposomal formulation is developed in this report. First, SN38 was conjugated with lysophospholipid by using a cleavable disulfide bond linker. After that, the conjugate (SN38-SS-PC) was assembled into liposomes by thin film method. Dynamic light scattering (DLS) characterization indicated that SN38-SS-PC liposomes possessed a narrow size distribution (172.8 ± 10.5 nm) and negative charged zeta potential (-8.9 ± 0.3 mV). The results of storage and physiological stabilities showed that SN38-SS-PC liposomes was stable under different conditions. More importantly, a reduction responsive release of parent drug SN38 was observed in the medium containing glutathione (GSH). In addition, SN38-SS-PC liposomes had a much more rapid cellular uptake behavior against cancer cells. The enhanced anti-cancer efficacy of SN38-SS-PC liposomes was further demonstrated by in vitro cytotoxicity assay against MCF-7 and A549 cells. Under in vivo evaluation in 4 T1 xenograft tumor model, SN38-SS-PC liposomes were observed to have lower systemic toxicity and higher tumor inhibition rate of 53.3% compared with the commercialized SN38 prodrug Irinotecan (Ir). In summary, SN38-SS-PC liposomes could be a promising redox responsive delivery system of SN38 for cancer therapy.
研究领域:
药学
·
肿瘤学
·
药物递送系统
·
生物药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2021
·
IF 4.939
Zhiting Sun,Xiaoxiao Wang,Jing Liu,Zhihong Wang,Weiwei Wang,Deling Kong,Xigang Leng
Photodynamic therapy (PDT) is promising for clinical cancer therapy; however, the efficacy was limited as an individual treatment regimen. Here, an approach synergistically combining PDT and nitric oxide (NO) gas therapy along with destruction of the tumor extracellular matrix (ECM) was presented to eliminate cancer. Specifically, the NO donor l-arginine (l-Arg) and the photosensitizer indocyanine green (ICG) were co-encapsulated in poly(lactic-glycolic acid) (PLGA) nanoparticles and then loaded into the poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL–PEG–PCL) hydrogel to develop an injectable, thermosensitive dual drug delivery system (PLGA@ICG@l-Arg/Gel). Significantly, reactive oxygen species (ROS) produced by PLGA@ICG@l-Arg/Gel under near-infrared (NIR) light irradiation could not only result in the apoptosis of cancer cells but also oxidize l-Arg to generate NO, which could suppress the proliferation of cancer cells. Moreover, ROS could further oxidize NO to generate peroxynitrite anions (ONOO–). ONOO– could activate matrix metalloproteinases (MMPs), which notably degraded collagen in ECM so as to damage the tumor microenvironment. PLGA@ICG@l-Arg/Gel significantly increased the antitumor efficacy against highly malignant 4T1 tumors in mice. Taken together, PLGA@ICG@l-Arg/Gel is a multifunctional platform that provides a novel strategy for cancer treatment with cascade amplification of the ROS oxidation effect, which holds great potential in clinical translation.
研究领域:
癌症治疗
·
药物递送系统
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2021
·Vol. 13
·期 9
·4855-4870
·
IF 7.79
Qifang Chen,Xianbin Ma,Li Xie,Wenjie Chen,Zhigang Xu,Erqun Song,Xiaokang Zhu,Yang Song
Ferroptosis therapy, which applies ferroptotic inducers to produce lethal lipid peroxidation and induce the death of tumor cells, is regarded as a promising therapeutic strategy for cancer treatment. However, there is still a challenge regarding how to increase reactive oxygen species (ROS) accumulation in the tumor microenvironment (TME) to enhance antitumor efficacy. Herein, we designed a nanosystem coated with the FDA approved poly(lactic-co-glycolic acid) (PLGA) containing ferrous ferric oxide (Fe3O4) and chlorin E6 (Ce6) for synergistic ferroptosis-photodynamic anticancer therapy. The Fe3O4-PLGA-Ce6 nanosystem can dissociate in the acidic TME to release ferrous/ferric ions and Ce6. Then, the Fenton reaction between the released ferrous/ferric ions and intracellular excess hydrogen peroxide can occur to produce hydroxyl radicals (˙OH) and induce tumor cell ferroptosis. The released Ce6 can increase the generation and accumulation of ROS under laser irradiation to offer photodynamic therapy, which can boost ferroptosis in 4T1 cells. Moreover, magnetic monodisperse Fe3O4 loading provides excellent T2-weighted magnetic resonance imaging (MRI) properties. The Fe3O4-PLGA-Ce6 nanosystem possesses MRI ability and highly efficient tumor suppression with high biocompatibility in vivo due to the synergism of photodynamic and ferroptosis antitumor therapies.
研究领域:
纳米技术
·
癌症治疗
·
磁共振成像
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2022
·Vol. 34
·期 37
·2204585
·
IF 32.086
Xiu Zhao,Yiyang Wang,Wenxiao Jiang,Qiongwei Wang,Jun Li,Zhiyang Wen,Airong Li,Kaixiang Zhang,Zhenzhong Zhang,Jinjin Shi,Junjie Liu
Virus-based immunotherapy is a promising approach to treat tumor. Closely mimicking the structure and sequential infection processes of natural viruses is highly desirable for effective tumor immunotherapy but remains challenging. Here, inspired by the robust innate immunity induced by herpesvirus, a herpesvirus-mimicking nanoparticle (named Vir-ZM@TD) is engineered for tumor therapy by mimicking the structure and infection processes of herpesvirus. In this biomimetic system, DNAzyme-loaded manganese‑doped zeolitic imidazolate framework‑90 (ZIF-90) nanoparticles (ZM@TD) mimic the virus nucleocapsid containing the genome; the erythrocyte membrane mimics the viral envelope; and two functional peptides, RGD and HA2 peptides, resemble the surface glycoprotein spikes of herpesvirus. Vir-ZM@TD can both effectively evade rapid clearance in the blood circulation and closely mimic the serial infection processes of herpesvirus, including specific tumor targeting, membrane fusion-mediated endosomal escape, and TFAM (transcription factor A, mitochondrial) deficiency-triggered mitochondrial DNA stress, as well as the release of manganese ions (Mn 2+ ) from organelles into the cytosol, ultimately effectively priming cGAS-STING pathway-mediated innate immunity with 68% complete regression of primary tumors and extending by 32 days the median survival time of 4T1-tumor-bearing mice.
研究领域:
生物医学工程
·
癌症免疫疗法
·
纳米技术
·
分子生物学
·
细胞生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2022
·
IF 10.761
Huijia Mao,Yangyang Wen,Yonghui Yu,Hongyan Li,Jing Wang,Baoguo Sun
Chemodynamic therapy (CDT) is a promising tumor-specific treatment, but still suffering insufficient reactive oxygen species (ROS) levels due to its limited efficacy of Fenton/Fenton-like reaction. Polyphenol, as a natural reductant, has been applied to promote the efficacy of Fenton/Fenton-like reactions; however, its intrinsic pro-apoptosis effects was ignored. Herein, a novel CDT/polyphenol-combined strategy was designed, based on Avenanthramide C-loaded dendritic mesoporous silica (DMSN)-Au/Fe 3 O 4 nanoplatforms with folic acid modification for tumor-site targeting. For the first time, we showed that the nanocomplex (DMSNAF-AVC-FA) induced ROS production in the cytoplasm via Au/Fe 3 O 4 -mediated Fenton reactions and externally damaged the mitochondrial membrane; simultaneously, the resultant increased mitochondrial membrane permeability can facilitate the migration of AVC into mitochondrial, targeting the DDX3 pathway and impairing the electron transport chain (ETC) complexes, which significantly boosted the endogenous ROS levels inside the mitochondrial. Under the elevated oxidative stress level via both intra- and extra-mitochondrial ROS production, the maximum mitochondrial membrane permeability was achieved by up-regulation of Bax/Bcl-2, and thereby led to massive release of Cytochrome C and maximum tumor cell apoptosis via Caspase-3 pathway. As a result, the as-designed strategy achieved synergistic cytotoxicity to 4T1 tumor cells with the cell apoptosis rate of 99.12% in vitro and the tumor growth inhibition rate of 63.3% in vivo , while very minor cytotoxicity to normal cells with cell viability of 95.4%. This work evidenced that natural bioactive compounds are powerful for synergistically boosting ROS level, providing new insight for accelerating the clinical conversion progress of CDT with minimal side effects.
研究领域:
癌症治疗
·
纳米技术
·
药学
·
生物化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2023
·
IF 9.9
Yunchao Zhao,Tian Huang,Shaobo Wang,Shuncheng Yao,Quanhong Hu,Xingyi Wan,Ning Guo,Yang Zhang,Linlin Li
Sonodynamic therapy (SDT) is considered as a new-rising strategy for cancer therapeutics, but the inefficient production of reactive oxygen species (ROS) by current sonosensitizers seriously hinders its further applications. Herein, a piezoelectric nanoplatform is fabricated for enhancing SDT against cancer, in which manganese oxide (MnO x ) with multiple enzyme-like activities is loaded on the surface of piezoelectric bismuth oxychloride nanosheets (BiOCl NSs) to form a heterojunction . When exposed to ultrasound (US) irradiation, piezotronic effect can remarkably promote the separation and transport of US-induced free charges, and further enhance ROS generation in SDT. Meanwhile, the nanoplatform shows multiple enzyme-like activities from MnO x , which can not only downregulate the intracellular glutathione (GSH) level, but also disintegrate endogenous hydrogen peroxide (H 2 O 2 ) to generate oxygen (O 2 ) and hydroxyl radicals (•OH). As a result, the anticancer nanoplatform substantially boosts ROS generation and reverses tumor hypoxia . Ultimately, it reveals remarkable biocompatibility and tumor suppression in a murine model of 4 T1 breast cancer under US irradiation. This work provides a feasible pathway for improving SDT using piezoelectric platforms.
研究领域:
纳米技术
·
癌症治疗
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Yufei Liu,Yao Qi,Chen Chen,Yincheng Jin,Shi Du,Jianan Qiao,Jing Yao
Tumor recurrence mainly triggered by tumor residual cells significantly contributes to mortality following breast tumor resection, and meanwhile post-surgical bacterial wound infections may accelerate tumor recurrence due to a series of infection-related complications. In this study, a nano-sensor system, Van-ICG@PLT, is constructed by a membrane camouflage and small molecule drug self-assembly strategy. This nano-sensor harnesses the innate tropism of platelets (PLT) to deliver vancomycin (Van) and indocyanine green (ICG) to surgical incisions, effectively eliminating both residual tumor cells and bacterial infections. Our findings demonstrate that Van-ICG@PLT preferentially accumulates at surgical wound. Under near-infrared (NIR) laser irradiation, Van-ICG@PLT exhibits significant cytotoxicity against 4T1 cells. Additionally, it is found to significantly promote ROS production thus inhibiting Staphylococcus aureus ( S. aureus ) growth, underscoring the synergistic benefits of phototherapy in combination with antibiotic treatment. In the 4T1 post-surgery recurrence mice model, Van-ICG@PLT is shown to efficiently ablate tumors in tumor-bearing mice (tumor inhibition rate of about 83%), and it demonstrates an excellent anti-infective effect in mice abscess models. Taken together, Van-ICG@PLT represents a promising paradigm in post-surgical adjuvant therapy (PAT). Its dual benefit in inhibiting cancer growth and promoting antibacterial activity makes Van-ICG@PLT a valuable addition to the existing arsenal of therapeutic options available for breast cancer patients.
研究领域:
癌症生物学
·
纳米技术
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Yiqian Wang,Yuzhi Qiu,Sihan Chen,Jinzhao Huang,Xiuwen Hu,Jiawen Chen,Sheng Wang,Xiangliang Yang,Yan Zhang,Yanhong Zhu
Systemically administered drugs often lead to off-target delivery, inducing compromised therapy efficacy and significant toxicity. We hypothesize that improving the drugs’ targeting and spatiotemporally controllable releasing capabilities can enhance the anti-tumor effects and reduce the side effects. To achieve this goal, a functionalized biomimetic photoactivatable nanotherapeutics (U-ACPT@MM) is designed. The U-ACPT@MM comprises of melittin, a pore-forming protein, functionalized within the 4 T1 tumor cell membrane, camouflaged with lanthanide-doped upconversion nanoparticles (UCNPs) conjugated with 9-aminocamptothecin (ACPT), a chemotherapeutics, by photolabile linkers. The melittin-functionalized 4 T1 tumor cell membrane not only enables homologous targeting ability to 4 T1 tumors, but also increases both the concentration of melittin and ACPT within tumor. Meanwhile, upon 808 nm irradiation, the UV emissions from UCNPs cut off photolabile linker to release ACPT. The synergism of enhanced tumor targeting and combinational therapeutic effects of ACPT and melittin leads to significant inhibition of 4 T1 tumor and lung metastasis with reduced side effects in vivo . Thus, our study provides a promising functional biomimetic photoactivatable nano-therapeutical strategy for cancer therapy.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
高影响因子
ACS Nano
·
2024
·
IF 15.8
Weiya Zeng,Ying Wang,Qing Zhang,Chengyi Hu,Jing Li,Jinwei Feng,Chenglu Hu,Yong Su,Jie Lou,Ling Long,Xing Zhou
Cancer metastasis is the main cause of cancer-related deaths and involves the interaction between tumor cells and neutrophils. In this study, we developed activated neutrophil membrane-coated nanoparticles (aNEM NPs) as nanodecoys to block neutrophil-mediated cancer metastasis. The aNEM NPs were fabricated by cloaking poly(lactic acid) nanoparticles with membranes derived from activated neutrophils and inherited the functional proteins of activated neutrophils. We demonstrated that aNEM NPs could interfere with the recruitment of neutrophils to the primary tumor and premetastatic niches, inhibit the adhesion of neutrophils to tumor vascular endothelium and circulating tumor cells (CTCs), and disrupt the formation of CTC–neutrophil clusters in vitro and in vivo. In 4T1-bearing mice, aNEM NPs could effectively reduce breast cancer metastasis to various organs in mice. Our results suggest that aNEM NPs are a promising nanomedicine for preventing or treating cancer metastasis by acting as neutrophil nanodecoys.
研究领域:
肿瘤学
·
纳米医学
·
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
JOURNAL OF CONTROLLED RELEASE
·
2020
·
IF 7.727
Xiaoye Yang,Xiaoqun Shi,Yanan Zhang,Jiangkang Xu,Jianbo Ji,Lei Ye,Fan Yi,Guangxi Zhai
To improve the anti-cancer therapeutic effect of nanosystems for chemo-photodynamic therapy, there remain several hurdles to be addressed, e.g. , limited co-loading efficiency, insufficient stimulus-responsiveness and lack of synergetic effect. This work reported novel reactive‑oxygen-species (ROS)-responsive chlorin e6 (Ce6) and paclitaxel (PTX) co -encapsulated chondroitin sulfate- g -poly (propylene sulfide) nanoparticles (CP/ChS- g -PPS NPs), wherein the drug loading efficiencies of Ce6 and PTX were as high as 14.93% and 24.31%, respectively. To enlarge the ROS signal at tumor sites thus enhancing the ROS-responsiveness of ChS- g -PPS NPs, near-infrared (NIR) light was utilized to induce Ce6 to produce more ROS to destruct the NPs. Our data showed that the photo-triggered self-destructive property of NPs helped drugs to spread deeper in tumors upon laser irradiation, making the NPs promising to thoroughly remove tumor cells. CP/ChS- g -PPS NPs exhibited a synergetic chemo-photodynamic therapy effect in vitro , which was suggested by the combination indexes of PTX and Ce6 lower than 1 when 20–80% inhibition rates of MCF-7 cells were achieved. As for the in vivo antitumor activity , the tumor inhibition rates of CP/ChS- g -PPS NPs (with laser irradiation) were as high as 92.76% and 88.57% in 4T1 bearing BALB/c mice and MCF-7 bearing BALB/c nude mice, respectively, which were significantly higher than those of other treatment groups. This work provided a simple yet effective strategy to develop photo-triggered ROS-responsive NPs for synergetic chemo-photodynamic therapy with quick ROS-responsive self-destruction, spatiotemporally controllability, reduced off-target toxicity, and desirable therapeutic effect.
研究领域:
药学
·
纳米技术
·
癌症治疗
·
生物医学工程
✓ 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）