ACS Nano
·
2019
·
IF 13.903
Xin Pang,Qicai Xiao,Yi Cheng,En Ren,Lanlan Lian,Yang Zhang,Haiyan Gao,Xiaoyong Wang,Wingnang Leung,Xiaoyuan Chen,Gang Liu,Chuanshan Xu
Rapid emergence of multidrug resistant (MDR) “superbugs” poses a severe threat to global health. Notably, undeveloped diagnosis and concomitant treatment failure remain highly challenging. Herein, we report a sonotheranostic strategy to achieve bacteria-specific labeling and visualized sonodynamic therapy (SDT). Using maltohexaose-decorated cholesterol and bacteria-responsive lipid compositions, a smart nanoliposomes platform (MLP18) was developed for precise delivery of purpurin 18, a potent sonosensitizer proved in this study. Taking advantage of the bacteria-specific maltodextrin transport pathway, the prepared MLP18 can specifically target the bacterial infection site and accurately distinguish the foci from sterile inflammation or cancer with a highly selective fluorescence/photoacoustic signal on the bacteria-infected site of mice. Moreover, the bacteria-responsive feature of MLP18 activated an efficient release and internalization of high concentration sonosensitizer into bacterial cells, resulting in effective sonodynamic elimination of MDR bacteria. In situ MRI monitoring visualized such potent sonodynamic activity and indicated that MLP18-mediated SDT could successfully eradicate inflammation and abscess from mice with bacterial myositis. In view of the above advantages, the developed nanoliposomes may serve as a promising sonotheranostic platform against MDR bacteria in the areas of healthcare.
研究领域:
纳米医学
·
诊疗学
·
传染病学
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药学科学
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生物医学工程
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DOI
PubMed
高影响因子
Small
·
2023
·Vol. 19
·期 24
·2300327
·
IF 13.3
Yiming Ding,Yunchao Zhao,Shuncheng Yao,Shaobo Wang,Xingyi Wan,Quanhong Hu,Linlin Li
Sonodynamic therapy (SDT) is regarded as a new-rising strategy for cancer treatment with low invasiveness and high tissue penetration, but the scarcity of high-efficiency sonosensitizers has seriously hindered its application. Herein, the iron-doped and oxygen-deficient bismuth tungstate nanosheets (BWO-Fe NSs) with piezotronic effect are synthesized for enhanced SDT. Due to the existence of oxygen defects introduced through Fe doping, the bandgap of BWO-Fe is significantly narrowed so that BWO-Fe can be more easily activated by exogenous ultrasound (US). The oxygen defects acting as the electron traps inhibit the recombination of US-induced electrons and holes. More importantly, the dynamically renewed piezoelectric potential facilitates the migration of electrons and holes to opposite side and causes energy band bending, which further promotes the production of reactive oxygen species. Furthermore, Fe doping endows BWO-Fe with Fenton reactivity, which converts hydrogen peroxide (H 2 O 2 ) in tumor microenvironment into hydroxyl radicals (•OH), thereby amplifying the cellular oxidative damage and enhancing SDT. Both in vitro and in vivo experiments illustrate their high cytotoxicity and tumor suppression rate against refractory breast cancer in mice. This work may provide an alternative strategy to develop oxygen-deficient piezoelectric sonosensitizers for enhanced SDT via doping metal ions.
研究领域:
纳米技术
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生物医学工程
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癌症研究
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材料科学
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诊疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2022
·Vol. 18
·期 31
·2202921
·
IF 15.153
Kexin Bian,Weitao Yang,Yan Xu,Weiwei Zeng,Hui Wang,Hongying Liang,Tianming Cui,Zhuo Wang,Bingbo Zhang
Sonosensitizers-assisted sonodynamic therapy (SDT) has been emerging as a promising treatment for cancers, and yet few specific regulations of band structure of sonosensitizers have been reported in relation to oxygen in tissues. Herein, by a gradient doping technique to modulate the band structure of hetero-semiconductor nanorods, it is found that the reduction potential of band-edge is very critical to reactive oxygen species (ROS) production under low-intensity ultrasound (US) irradiation and particularly, when aligned with the reduction of oxygen, ROS generation is found to be most significantly enhanced. Withal, US-generated oxidation holes are found to be effective in consuming overexpressed glutathione in tumor lesions, which amplifies cellular oxidative stress and finally induces tumor cell death. Moreover, the intrinsic fluorescence property of semiconductors provides imaging capability to illumine tumor area and guide the SDT process. This study demonstrates that the reduction potential state of sonosensitizers is of crucial importance in ROS generation and the proposed reduction potential-tailored hetero-semiconductor nanorods materialize low-intensity US irradiation yet highly effective SDT and synergetic hole therapy of tumors with imaging guidance and reduced radiation injury.
研究领域:
癌症治疗
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纳米技术
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材料科学
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生物医学工程
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超声治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Xinxin Zhang,Jimin Huang,Jinzhou Huang,Zhe Shi,Huicong Niu,Yi Zheng,Xiao Wang,Chengtie Wu,Jiajie Chen,Ping Liu,Yufang Zhu
The simultaneous inhibition of tumor recurrence and promotion of wound healing are critical for patients undergoing melanoma surgery. However, the development of an effective yet straightforward platform that meets the comprehensive therapeutic requirements of clinical melanoma postoperative care still remains a significant challenge. Herein, a 2D semiconductive MnPSe 3 nanosheets (MPS NSs)-engineered sodium alginate (SA) hydrogel dressing (SA-MPS) is developed. The MPS NSs, a member of the ternary transition metal phosphorous chalcogenides (TMPCs), are successfully prepared through an ultrasonic-assisted liquid phase exfoliation approach from bulk MnPSe 3 . These nanosheets exhibit the integrative functions of sonosensitizers, Fenton-like catalysts, glutathione (GSH) scavengers, and phosphorus (P)/selenium (Se)-containing nutrients. In vitro and in vivo evaluations demonstrate that the SA-MPS hydrogel dressing possesses excellent biocompatibility and is effective for combined sonodynamic/chemodynamic therapy (SDT/CDT) of tumors, with amplified reactive oxygen species (ROS) production. Additionally, it promotes skin regeneration in postoperative wounds by supplying bioactive P/Se elements. Hence, such a multifunctional SA-MPS hydrogel dressing without complex integration offers great potential for suppressing postoperative melanoma recurrence while facilitating wound healing, making it a promising candidate for melanoma postoperative care.
研究领域:
生物医学工程
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材料科学
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肿瘤学
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纳米技术
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治疗学
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Hongwei Xiang,Bin Shen,Chunmei Zhang,Rui Li
Introduction Cell death regulation holds a unique value in the field of cancer therapy. Recently, disulfidptosis has garnered substantial scientific attention. Previous studies have reported that sonodynamic therapy (SDT) based on reactive oxygen species (ROS) can regulate cancer cell death, achieving an limited anti-cancer effect. However, the integration of SDT with disulfidptosis as an anti-cancer strategy has not been extensively developed. In this study, we constructed an artificial membrane disulfidptosis sonosensitizer, specifically, a nanoliposome (SC@lip) coated with a combination of the chemotherapy medicine Sorafenib (Sora) and sonosensitizer Chlorin e6 (Ce6), to realize a one-stop enhanced SDT effect that induces disulfidptosis-like cancer cell death.Methods Sorafenib and Ce6 were co-encapsulated into PEG-modified liposomes, and SC@Lip was constructed using a simple rotary evaporation phacoemulsification method. The cell phagocytosis, ROS generation ability, glutathione (GSH) depletion ability, lipid peroxidation (LPO), and disulfidptosis-like death mediated by SC@Lip under ultrasound (US) irradiation were evaluated. Based on a 4T1 subcutaneous tumor model, both the in vivo biological safety assessment and the efficacy of SDT were assessed.Results SC@Lip exhibits high efficiency in cellular phagocytosis. After being endocytosed by 4T1 cells, abundant ROS were produced under SDT activation, and the cell survival rates were below 5%. When applied to a 4T1 subcutaneous tumor model, the enhanced SDT mediated by SC@Lip inhibited tumor growth and prolonged the survival time of mice. In vitro and in vivo experiments show that SC@Lip can enhance the SDT effect and trigger disulfidptosis-like cancer cell death, thus achieving anti-tumor efficacy both in vitro and in vivo.Conclusion SC@Lip is a multifunctional nanoplatform with an artificial membrane, which can integrate the functions of sonosensitization and GSH depletion into a biocompatible nanoplatform, and can be used to enhance the SDT effect and promote disulfidptosis-like cancer cell death.
研究领域:
癌症治疗
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纳米技术
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细胞生物学
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药学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Pengying Wu,Zhen Ya,Yan Li,Mingting Zhu,Lei Zhang,Yujin Zong,Shifang Guo,Mingxi Wan
The combination of checkpoint blockade with focused ultrasound (FUS) physical therapy can enhance antitumor immune response by improving the precision and efficiency of immunotherapy. However, one of the major disadvantages of conventional FUS treatment is the small lesion size, which prolongs treatment duration. We constructed a focused acoustic vortex (FAV) system with a hollow cylindrical focal region, which exhibited a larger focal region compared to conventional FUS of the same frequency. We developed an all-in-one synergistic therapy against metastatic breast cancer based on integrated FAV double combination sequence-regulated phase-transformation nanodroplets (CPDA@PFH) with checkpoint blockade immunotherapy. A single treatment with FAV + CPDA@PFH resulted in 2.25-fold higher inhibition of tumor growth compared to that with FUS + CPDA@PFH. In addition, FAV-regulated CPDA@PFH combined with ICB induced a systemic immune response that not only inhibited the growth of primary (98.41% inhibition rate) and distal (80.71%) 4T1 tumors but also reduced the progression of lung metastasis. In addition, the synergistic therapy achieved long-term immune memory that effectively prevented tumor growth and improved the survival time of mice. The long-term survival rate of 4T1 tumor-bearing mice treated with FAV + CPDA@PFH + Anti-PD-L1 was 57.14% on day 60 after treatment. Our study is a proof-of-concept of cascade-amplified synergistic tumor therapeutics based on ultrasonic-hyperthermia, cavitation, sonodynamic therapy (SDT), and checkpoint blockade immunotherapy through FAV-regulated CPDA@PFH phase-transformation nanodroplets.
研究领域:
肿瘤学
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生物医学工程
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免疫疗法
·
诊疗一体化
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale Horizons
·
2024
·
IF 8
Yue Chen,Tong Ding,Zhengzheng Qian,Zerui Ma,Liming Zhou,Zhiling Li,Runkai Lv,Yinghui Xu,Yingjie Xu,Linhui Hao,Chen Zhu,Xikuang Yao,Wenying Yu,Wenpei Fan
Sonodynamic therapy (SDT) is gaining popularity in cancer treatment due to its superior controllability and high tissue permeability. Nonetheless, the efficacy of SDT is severely diminished by the transient generation of limited reactive oxygen species (ROS). Herein, we introduce an acid-activated nanosonosensitizer, CaO2@PCN, by the controllable coating of porphyrinic metal-organic frameworks (PCN-224) on CaO2 to induce cascaded oxidative stress in tumors. The PCN-224 doping could generate ROS during SDT to induce intracellular oxidative stress and abnormal calcium channels. Meanwhile, the ultrasound also promotes extracellular calcium influx. In addition, the CaO2@PCN will sequentially degrade in the tumor cell lysosomes, releasing Ca2+ and H2O2 to induce further abnormal calcium channels and elevate the levels of Ca2+. Insufficient catalase (CAT) in tumor cells promotes intracellular calcium overload, which can induce persistent ROS generation and mitochondrial dysfunction through ion interference therapy (IIT). More importantly, PCN-224 also protects CaO2 against significant degradation under neutral conditions. Hence, the well-designed CaO2@PCN produces synergistic SDT/IIT effects and persistent ROS against cancer. More notably, the acidity-responsive biodegradability endows CaO2@PCN with excellent biosafety and promising clinical potential.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2024
·
IF 5.8
Xinru Kong,Yanxi Yang,Xueli Ren,Yandai Lin,Yu Shi,Zhe Liu
The concept of combining external medical stimuli with internal functional biomaterials to serve cancer-oriented treatments is emergingly developed. Optical and acoustical activations have shown special promises as non-invasive regulation modalities in cancer treatment and intervention. It is always challenging to leverage their contributions between optical and acoustical stimuli and find the appropriate biomaterials to optimally match them. Herein, a type of hybrid nanomicelles (ICG@PEP@HA) containing ICG as photo/sonosensitizers, an amphiphilic peptide for membrane penetration and hyaluronic acid for cluster determinant 44 (CD44) targeting were fabricated. Triggered by external stimuli of laser and US irradiations, their photo/sonothermal performances, in vitro reactive oxygen species (ROS) production capabilities and tumor-targeting efficiency have been systematically evaluated. It was interestingly found that the external stimulus of laser induced more quantity of ROS which resulted in a significant cell apoptosis and tumor growth inhibition in the presence of ICG@PEP@HA. The individual analysis and corresponding rationales have been investigated. In the meanwhile, these hybrid nanomicelles were administered into the MDA-MB-231 tumor-bearing nude mice for PDT and SDT therapies and their biocompatibility assessment, and a PDT prevailing efficacy and reliable bio-safety have been evidenced based on the hematological analysis and histochemical stainings. In summary, this study has validated a novel pathway to utilize these hybrid nanomicelles for laser/US-triggered localized tumor treatments, and the treatment efficiency may be leveraged by different external stimuli sources. It is also expected to give birth to full accessibility to clinical translations for human cancer treatments by means of as-reported laser/US-nanomicelles combination strategy.
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Meiting Li,Yaqian Zhang,Xiaoge Zhang,Zhuoyin Liu,Junjie Tang,Miao Feng,Baizhu Chen,Dalin Wu,Jie Liu
Sonodynamic therapy (SDT) benefiting from its intrinsic merits, such as noninvasiveness and deep tissue penetrability, is receiving increasing considerable attention in reactive oxygen species (ROS)-based tumor treatment. However, current sonosensitizers usually suffer from low tumor lesion accumulation, insufficient ROS generation efficiency under ultrasound, and non-biodegradability, which seriously impede the therapeutic outcomes. Additionally, it is difficult that SDT alone can completely eradicate tumors because of the complex and immunosuppressive tumor microenvironment (TME). Herein, we simultaneously employ sonosensitive porphyrin building blocks and glutathione (GSH)-responsive disulfide bonds to construct a novel degradable multifunctional porphyrin-based hollow porous organic polymer (POP) nanosonosensitizer (H-Pys-HA@M/R), which combine SDT, “on-demand” chemotherapy, and immunotherapy. Taking the unique advantages of POPs with designable structures and high specific surface area, this H-Pys-HA@M/R nanosonosensitizer can achieve tumor target accumulation, GSH-triggered drug release, and low-frequency ultrasound-activating ROS generation with encouraging results. Furthermore, this multifunctional nanosonosensitizer can effectively evoke immunogenic cell death (ICD) response through the combination of SDT and chemotherapy for both primary and distal tumor growth suppression. Meanwhile, H-Pys-HA@M/R exhibits favorable biodegradation and biosafety. Therefore, this study provides a new strategy for reasonably designing and constructing POP-related sonosensitizers combining SDT/chemotherapy/immunotherapy triple treatment modalities to eradicate malignant tumors.
研究领域:
生物医学工程
·
癌症治疗
·
纳米技术
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2021
·Vol. 9
·期 11
·3989-4004
·
IF 6.843
Yanan Zhang,Na Qiu,Yu Zhang,Huixian Yan,Jianbo Ji,Yanwei Xi,Xiaoye Yang,Xiaogang Zhao,Guangxi Zhai
Sonodynamic therapy (SDT) is a promising non-invasive approach for cancer therapy. However, tumor hypoxia, a pathological characteristic of most solid tumor types, poses a major challenge in the application of SDT. In this study, a novel CD44 receptor-targeted and redox/ultrasound-responsive oxygen-carrying nanoplatform was constructed using chondroitin sulfate (CS), reactive oxygen species (ROS)-generating sonosensitizer Rhein (Rh), and perfluorocarbon (PFC). Perfluoroalkyl groups introduced into the structures preserved the oxygen carrying ability of PFC, increasing the oxygen content in B16F10 melanoma cells and enhancing the efficiency of SDT. Controlled nanoparticles without PFC generated lower ROS levels and exerted inferior tumor inhibition effects, both in vitro and in vivo, under ultrasound-treatment. In addition, SDT promoted immunogenic cell death (ICD) by inducing exposure of calreticulin (CRT) after treatment with CS–Rh–PFC nanoparticles (NPs). The immune system was significantly activated by docetaxel (DTX)-loaded NPs after SDT treatment due to the enhanced secretion of IFN-γ, TNF-α, IL-2 and IL-6 cytokines and tumor-infiltrating CD4+ and CD8+ T cell contents. Our findings support the utility of CS–Rh–PFC as an effective anti-tumor nanoplatform that promotes general immunity and accommodates multiple hydrophobic drugs to enhance the beneficial effects of chemo-SDT therapy.
研究领域:
癌症治疗
·
纳米技术
·
免疫学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Xun Guo,Peng Tu,Leilei Zhu,Chen Cheng,Weixi Jiang,Chier Du,Xiaoting Wang,Xiaoling Qiu,Yuanli Luo,Li Wan,Rui Tang,Haitao Ran,Zhigang Wang,Jianli Ren
Cancer multidrug resistance (MDR) is an important reason that results in chemotherapy failure. As a main mechanism of MDR, overexpressed P-glycoprotein (P-gp) utilizes adenosine triphosphate (ATP) to actively pump chemotherapy drugs out of cells. In addition, metabolic reprogramming of drug-resistant tumor cells (DRTCs) exacerbates the specific hypoxic microenvironment and promotes tumor metastasis and recurrence. Therefore, we propose a novel sonodynamic therapy (SDT) paradigm to induce energy metabolism disorder and drug resistance change of DRTCs. A US-controlled “Nanoenabled Energy Metabolism Jammer” (TL@HPN) is designed using perfluoropentane (PFP) adsorbing oxygen in the core, and a targeting peptide (CGNKRTR) is attached to the liposome as the delivery carrier shell to incorporate hematoporphyrin monomethyl ether (HMME) and paclitaxel (PTX). The TL@HPN with ultrasonic/photoacoustic imaging (PAI/USI) precisely controlled the release of drugs and oxygen after being triggered by ultrasound (US), which attenuated the hypoxic microenvironment. SDT boosted the reactive oxygen species (ROS) content in tumor tissues, preferentially inducing mitochondrial apoptosis and maximizing immunogenic cell death (ICD). Persistently elevated oxidative stress levels inhibited ATP production and downregulated P-gp expression by disrupting the redox balance and electron transfer of the respiratory chain. We varied the effect of TL@HPN combined with PD-1/PD-L1 to activate autoimmunity and inhibit tumor metastasis, providing a practical strategy for expanding the use of SDT-mediated tumor energy metabolism.
研究领域:
肿瘤学
·
药理学
·
治疗学
·
免疫学
·
医学影像学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Xingyue Yang,Ren Fang,Xiaotian Li,Weihao Kong,Yubao Jin,Ruohan Jiao,Zhenggong Liu,Meiqi Zhang,Qixian Peng,Yumiao Zhang,Ningning Song
The clinical treatment of hospital-acquired persistent osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) presents two major challenges: ineffective drug delivery into deep tissues and counteracting the rapid establishment of an immunosuppressive microenvironment. Indeed, MRSA can evade immunosurveillance and undermine both innate and adaptive immune responses. Herein, the engineered nanovesicles, functioning by combining sonodynamic therapy (SDT) with immune modulation, were constructed for the precise and noninvasive removal of MRSA in deep tissue and activation of the antimicrobial immune response using a newly engineered nanovesicle. Macrophage-derived M1 phenotypic microvesicles (M1-MW) internalized vancomycin-cross-linked micelles with the acoustic sensitizer indocyanine green (ICG) (VCG micelles). The vesicles of M1-MW were grafted with PEGylated mannose, allowing for targeted accumulation at the infection site. The VCG micelles were responsive to the highly reducing environment and released ICG to generate ROS after exposure to ultrasounds. This effect was combined with the presence of vancomycin to kill MRSA. In an osteomyelitis infection model, we observed an improved survival rate and reprogramming of macrophages to a pro-inflammatory M1 phenotype. The latter promoted T-cell activation and immune defense against MRSA-camouflaged homologous cell-transferred infections. Thus, our study presents a noninvasive and efficient treatment (VCG@MMW) for deep osteomyelitis with improved bacterial clearance and reduced risk of recurrence with enhanced immune response.
研究领域:
纳米技术
·
传染病学
·
免疫学
·
药学
·
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）