JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2025
·Vol. 29
·期 11
·e70636
·
IF 4.2
Hao Zhang,Guoyan Liu
Gastric cancer is a common malignant tumour. Copper‐induced cell death, a recently discovered form of metal ion‐related cell death, has garnered significant attention from researchers. We synthesised a multifunctional nanoparticle, ZnO@CuEA, and characterised its morphology using transmission electron microscopy. Cytotoxicity was analysed via CCK8 assays and calcein‐AM staining. The tumour‐targeting capability of ZnO@CuEA was validated using confocal microscopy and in vivo imaging experiments. RNA‐seq and proteomic analysis were conducted to assess changes in mRNA and protein expression before and after ZnO@CuEA treatment. Lysosomal β‐galactosidase staining was employed for cellular senescence detection, and protein expression levels were analysed via Western blot. Finally, in vivo experiments demonstrated the tumour‐inhibitory effect of ZnO@CuEA. ZnO@CuEA is a multifunctional nanoparticle capable of targeting tumour cells and inducing cuproptosis. In vivo experiments showed that ZnO@CuEA exhibits significant antitumor activity. The multifunctional nanoparticles synthesised in this study provide a novel therapeutic approach for cancer treatment.
研究领域:
肿瘤学
·
分子生物学
·
材料科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Xinxin Xie,Jinxia Zhang,Lihong Sun,Shuyu Xu,Shiti Sha Ma,Haonan Wang,Xiaoda Li,Qiong Xiang,Ligang Cui,Xiaolong Liang
Hypoxia is a common feature of malignant tumors, which can accelerate tumor growth and reduce the sensitivity of chemotherapy and sonodynamic therapy by activating the hypoxia-inducible factor (HIF) signaling pathway. In HER2-positive gastric cancer, HER2 overexpression enhances HIF-1α synthesis, exacerbating hypoxia and impairing sonodynamic therapy. It also reduces trastuzumab-mediated antibody-dependent cytotoxicity, significantly compromising therapeutic outcomes. Herein, pyropheophorbide-conjugated lipid (pyropheophorbide-lipid, PL) and trastuzumab were fabricated into targeted nanoparticles (TP NPs) for loading perfluorobromooctane (PFOB) carrying oxygen (TPPO NPs), thus enabling oxygen self-supplied sonodynamic and antibody therapies. In vitro experiments showed that antibody targeting significantly increased the cellular uptake of sonosensitizers, and the controlled release of oxygen was dependent on ultrasound parameters, greatly enhancing the killing effects of SDT and antibody therapy. In vivo animal experiments showed that TPPO NPs-mediated enhanced permeation and retention (EPR) effects, along with antibody targeting, improved the enrichment of sonosensitizers in tumors. Notably, ultrasound-triggered topical delivery of oxygen significantly alleviated tumor hypoxia and further improved the efficacy of SDT and antibody therapy. Given the good biosafety profile of TPPO NPs, this system holds great promise for future clinical applications in gastric cancer.
研究领域:
肿瘤学
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药剂学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
Materials Today Chemistry
·
2024
·
IF 6.7
Jinyu Wang,Qianqian Qiao,Yuqi Feng,Yuhao Guo,Tao Liao,Linwei Li,Ying Kuang,Bingbing Jiang,Ziqiang Xu,Cao Li
In cancer treatment, although prodrugs have been developed to overcome obstacles such as undesirable pharmacokinetic performance and serious off-target toxicity of most chemotherapeutics, the combination of prodrugs with nanotechnology could be used to overcome the shortcomings of conventional prodrug strategies and facilitate more efficient drug delivery and accumulation of anticancer prodrugs at specific sites/tissues. Phototherapy is a method that uses near-infrared (NIR) light to achieve local and non-invasive tumor therapy. The combination of chemotherapy and phototherapy has shown many therapeutic advantages, including synergistic therapeutic effects and the reduction of toxic and side effects of drugs through dose reduction. In this work, a hydrazone linkage was reported to conjugate Ti 3 C 2 T x MXene nanosheets with doxorubicin hydrochloride (DOX) and methoxy poly(ethylene glycol) benzaldehyde (mPEG-CHO) through a chemical surface modification to form a two-dimensional (2D) nano-prodrug Ti 3 C 2 T x -DOX/PEG (TDP) for synergistic chemo-photothermal therapy. First, hydrazide functionalized Ti 3 C 2 T x was obtained. Then, the carbonyl group of DOX and the aldehyde group of mPEG-CHO can form a pH-responsive hydrazone bond with hydrazide-functionalized Ti 3 C 2 T x . The high surface area of Ti 3 C 2 T x could overcome the reduced drug loading caused by conjugation. Aqueous stability and biocompatibility were enhanced by the introduction of PEG, making the material capable of prolonged circulation in the body's bloodstream. By achieving excellent antitumor results with this nano-prodrug, we have added another brick to the edifice of Ti 3 C 2 T x MXene as an anticancer drug carrier, and given new vitality to the study of anticancer prodrugs combined with nanotechnology.
研究领域:
肿瘤学
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纳米医学
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2017
·
IF 4.3
Caiying Zhu,Jingjing Xiao,Ming Tang,Hua Feng,Wulian Chen,Ming Du
The preparation of polymer therapeutics capable of controlled release of multiple chemotherapeutic drugs has remained a tough problem in synergistic combination cancer therapy. Herein, a novel dual-drug co-delivery system carrying doxorubicin (DOX) and platinum(IV) (Pt[IV]) was developed. An amphiphilic diblock copolymer, PCL-b-P(OEGMA-co-AzPMA), was synthesized and used as a nanoscale drug carrier in which DOX and Pt(IV) could be packaged together. The copolymers were shell cross-linked by Pt(IV) prodrug via a click reaction. Studies on the in vitro drug release and cellular uptake of the dual-drug co-delivery system showed that the micelles were effectively taken up by the cells and simultaneously released drugs in the cells. Futhermore, the co-delivery polymer nanoparticles caused much higher cell death in HeLa and A357 tumor cells than either the free drugs or single-drug-loaded micelles at the same dosage, exhibiting a synergistic combination of DOX and Pt(IV). The results obtained with the shell cross-linked micelles based on an anticancer drug used as a cross-linking linkage suggested a promising application of the micelles for multidrug delivery in combination cancer therapy.
研究领域:
肿瘤学
·
药剂学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Journal of Functional Biomaterials
·
2024
·Vol. 15
·期 12
·388
·
IF 5
Siwei Sun,Xinyi Hou,Ke Li,Chenqi Huang,Yu Rong,Jiao Bi,Xueping Li,Daocheng Wu
Metformin (Met) is one of the most commonly prescribed first-line drugs for diabetes treatment. However, it has several issues, including low bioavailability, therapeutic platform, and side effects at high doses. In order to improve the therapeutic efficiency of Met, this study proposes a strategy of using Met and curcumin (Cur) to prepare Cur-Zn(II)-Met infinite coordination polymer nanoparticles (CM ICP NPs), and combining this with intraperitoneal injections, for the treatment of diabetic mice. Fourier transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), nanoparticle analysis, cytotoxicity experiments, and mice experiments were used to investigate structure, properties, and application effects. The results showed that CM ICP NPs exhibit a high drug encapsulation rate (100%), good stability, and an absence of in vivo and in vitro toxicity. The blood glucose level of diabetic mice after treatment was reduced to 6.7 ± 0.65 mmol/L at the seventh week. In terms of therapeutic mechanism, it appears that Met and Cur can synergistically regulate blood glucose in mice from multiple paths. This study provides a promising method for the treatment of diabetes using Met and other drugs.
研究领域:
药理学
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生物医学工程
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代谢疾病研究
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产品关联
DOI
PubMed
高影响因子
Journal of Inorganic and Organometallic Polymers and Materials
·
2024
·
IF 3.9
Zhao Qiong,Duan Jianying
Membranous glomerulonephritis (MN) is clinically marked by significant proteinuria or nephrotic syndrome, and pathologically by a uniform thickening of the glomerular capillary basement membrane due to diffuse subepithelial immune complex deposition without notable cell proliferation. In this study, we synthesized a novel therapeutic agent, compound 1, designed for synergistic use with Eculizumab (Ecu) in MN treatment. To optimize the delivery and therapeutic effect of this combination, we developed an advanced composite drug carrier, mPEG-pHPMA@CP1@1@Ecu, incorporating methoxy polyethylene glycol (mPEG) and poly(2-hydroxypropyl methacrylamide) (pHPMA) with a metal-organic framework known as CP1. Structural and compositional integrity of this carrier was rigorously characterized. Our studies demonstrated that mPEG-pHPMA@CP1@1@Ecu could significantly mitigate hypoxia-induced renal tubular epithelial cell damage, highlighting the synergistic potential of compound 1 and Ecu. This new carrier system shows promising therapeutic potential for MN management.
研究领域:
医学
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药学
·
生物材料科学
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产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2019
·
IF 7.901
Cong Luo,Bingjun Sun,Chen Wang,Xuanbo Zhang,Yao Chen,Qin Chen,Han Yu,Hanqing Zhao,Mengchi Sun,Zhenbao Li,Haotian Zhang,Qiming Kan,Yongjun Wang,Zhonggui He,Jin Sun
There is an urgent need to develop efficient combination drug delivery approaches to address the low efficiency of clinical cancer monotherapy . However, how to achieve high-efficient synchronous co-delivery and synergistic therapy remains a big challenge. Herein, we report a self-facilitated nanoassembly of a heterotypic chemo-photodynamic dimer for multimodal cancer therapy. A reactive oxygen species (ROS)-responsive dimer of paclitaxel (PTX) and pyropheophorbide a (PPa) is rationally designed and synthesized. The “Two-in-One” dimer serves as both carrier material and cargo, could self-assemble into nanoparticles in water with ultrahigh co-loading capacity and self-facilitated ROS-responsive drug release. The endogenous ROS overproduced in tumor cells together with PPa-generated ROS under laser irradiation synergistically facilitate on-demand drug release from the nano-assembly. The disintegration of nanoassembly triggered by ROS effectively addresses the dilemma of aggregation-caused quenching (ACQ) effect of photosensitizer (PPa). Both in vitro and in vivo results suggest that PTX-initiated chemotherapy in combination with PPa-mediated PDT exhibits synergistic antitumor activity . Our findings provide a strategy for the rational design of nanocarrier for high-efficient synergetic cancer therapy.
研究领域:
肿瘤学
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药剂学
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2022
·
IF 5.112
Xiaowei Wang,Yanhong Liu,Yue Hu,Hong Gao,Meiling Ge,Jie Ding,Dongkai Wang
The synergistic therapy of malignant tumors with chemotherapy and photothermal therapy has attracted extensive researcher attention. With the further development of photosensitizers, photosensitizer delivery and stability are the urgent problem to be solved at present. In this study, the biodegradable hybrid micelles (HMs) nano system for co-delivery paclitaxel (PTX) and IR825, investigating the photosensitizer stability in the drug delivery system and therapeutic effectiveness in vitro or in vivo . The hybrid micelle (PTX/IR825-TAT HMs) was self-assembled through hydrophobic interactions between polyethyleneimine-polycaprolactone (PEI-PCL) and TAT peptide modifided-1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(polyethylene glycol) 5000 (TAT-PEG-DSPE). The results indicated that TAT HMs could successfully encapsulate IR825 PTX (PTX/IR825-TAT HMs). More importantly, IR825 encapsulated in hybrid micelles improved physiological stability, thermostability and photostability. In addition, the PTX released rapidly from PTX/IR825-TAT HMs in acidic and laser irradiation environments. In vitro cell analysis demonstrated that PTX/IR825-TAT HMs exhibited effective internalization of breast cancer cells. At the same time, PTX/IR825-TAT HMs with laser irradiation synergistically induced cancer cell apoptosis and death . indicating chemo-photothermal therapy synergistic therapeutic effect. In vivo antitumor studies showed that PTX/IR825-TAT HMs precisely reached the tumor tissue and convert light energy into heat energy under laser irradiation, PTX/IR825-TAT HMs had excellent synergistic antitumor efficiency compared to single chemotherapy and photothermal therapy.
研究领域:
药剂学
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肿瘤学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
Polymer Chemistry
·
2024
·Vol. 15
·期 28
·2883-2898
·
IF 4.1
Yaodong Di,Hanning Zhang,Zimu Luo,Congshu Feng,Xi Zhang,Shuai Yang,Jie Hou,Lesan Yan
In tumor treatment, traditional single therapies such as chemotherapy or photothermal therapy often suppress tumor growth while also causing serious toxic side effects on normal tissues and organs. Additionally, reducing drug dosage is challenging to achieve the desired therapeutic effects. Therefore, combining chemotherapy and photothermal therapy has become an effective strategy to enhance tumor treatment efficiency. To achieve this, a biodegradable amphiphilic block copolymer with carboxyl-functionalized side chains, named mPEG-b-P(CL-co-MPC/TMA), was designed and synthesized. It was then complexed with cisplatin to successfully prepare mPEG-b-P(CL-co-MPC/TMA)-Pt. Subsequently, the novel conjugated polymer photothermal agent PDPPDTP was encapsulated to prepare PDPPDTP-loaded mPEG-b-P(CL-co-MPC/TMA)-Pt nanomicelles. These nanomicelles not only co-deliver cisplatin drugs and photothermal agents but also exhibit excellent stability and photothermal performance. Under lower doses of cisplatin drugs and photothermal effects, they can still efficiently eradicate tumor cells in a relatively gentle manner, demonstrating significant potential in synergistic cancer therapy.
研究领域:
肿瘤学
·
生物材料学
·
药剂学
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Tonghao Ma,Qi Zhang,Qize Xuan,Jiafeng Zhuang,Wei Zhang,Hui Li,Chao Chen,Ping Wang
Currently, single chemotherapeutics or photosensitizers implemented in clinic present huge challenges in terms of unfavorable therapeutic efficacy, physiological instability and non-selective toxicity. In order to remedy the faultiness of insufficient efficiency of monotherapy, we herein synthesized an “all-in-one” targeting drug delivery system with multimodal therapy based on chemo-photodynamic synergistic therapy. Specifically, mesoporous silica nanorods were first synthesized through doping chlorin e6 (Ce6) in the sol–gel process, and then were used to load chemotherapy drug. After the amino groups and boronic acid groups were sequentially modified on the surface of nanoparticles, lactobionic acid (LA) was chosen as an intermediary to achieve simultaneous crosslinking of targeting agent LA and sealing agent sericin through pH responsive boronic ester linkage. The obtained ultimate nanocomposites possessed good biocompatibility, colloidal stability and hemocompatibility. Besides, in vitro endocytosis experiment performed with confocal laser scanning microscopy and flow cytometry testified the LA-mediated accurate tumor-specific targeting ability of synthesized nanocarriers. Moreover, a series of in vitro assays demonstrated that fabricated therapeutic nanoplatform could not only release loaded drugs in response to acidic environment to achieve chemotherapy, but also could generate singlet oxygen from photosensitizer Ce6 under external light stimulation to realize photodynamic therapy. Most interestingly, the combination therapy including photodynamic therapy and chemotherapy exhibited a synergistic effect against tumor cells in both in vivo and ex vivo experiments. Briefly, the drug delivery system reported here could attain effective chemo-photodynamic synergistic therapy to dispose of the insufficient lethality of monotherapy while guaranteeing the safety during in vivo application.
研究领域:
纳米医学
·
肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
MICROPOROUS AND MESOPOROUS MATERIALS
·
2020
·
IF 4.551
Renlu Han,Keqi Tang,Yafei Hou,Jiancheng Yu,Chenlu Wang,You Wang
A core/shell/shell structure nanoparticle with anticancer drug and dual-photosensitizer co-loading for synergistic chemotherapy and photodynamic therapy was developed. The nanoparticle contains an upconversion nanoparticle (UCNP) core, a middle silica shell with the first photosensitizer (PS) methylene blue (MB) encapsulated, and an outside mesoporous silica shell with the second PS rose bengal (RB) electrostatically attached to the channel walls and anticancer drug doxorubicin hydrochloride (DOX) uploaded into channel pores later. Cyclodextrine (CD) is next conjugated on the nanoparticle surface via acid-labile bond as gatekeeper to block pore openings and it can be dissociated in the acid microenvironment of cancer cells to release drug for Chemo. Upon near-infrared light irradiation, the upconverted red and green lights by UCNP core activate MB and RB simultaneously producing maximized singlet oxygen ( 1 O 2 ) for PDT to efficiently further kill the Chemo-treated cancer cells in a synergistic way. The anticancer effect of the nanoparticles was demonstrated both in vitro and in vivo . The combination of Chemo and PDT showed significantly enhanced therapeutic effect compared to single Chemo or PDT, endowing the core/shell/shell structure nanoparticle with a great potential for synergistic cancer treatments.
研究领域:
生物医学工程
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2013
·
IF 3.554
Yan Wang,Shurong Ma,Zhongshi Xie,Haishan Zhang
Doxorubicin was chemically conjugated to a biodegradable polymeric carrier as a polymer-doxorubicin (polymer-Dox) conjugate via an acid labile Schiff-base bond. Then, paclitaxel was physically encapsulated by the polymer-Dox conjugate to self assemble in water as micellar nanoparticles with both doxorubicin and paclitaxel in one nanoparticle. In this way, doxorubicin and paclitaxel were combined. The preparation of the polymer-doxorubicin conjugates, encapsulation of paclitaxel, characterization of nanoparticles was systematically studied and the biological evaluation of the free drug combination as well as the micellar platform combination in vitro was thoroughly detailed.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）