INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2021
·
IF 5.875
Zhimei Xiao,Bo Zhuang,Guoli Zhang,Miao Li,Yiguang Jin
Sonodynamic therapy (SDT) has been tried for cancer treatment; however, sonosensitizers are usually administered by injection, leading to low distribution in the tumor tissue and compromised therapeutic effect, even serious side effect. Here, we combined cationic liposomal hydroxycamptothecin (CLH) and 5-aminolevulinic acid (5-ALA) via intratracheal (i.t.) administration for the chemo-sonodynamic (Chemo-SDT) therapy of metastatic lung cancer. CLH was prepared from HCPT and the lipid mixture of soybean lecithin/cholesterol/octadecylamine with a film method. The optimal pre-incubation time of 5-ALA with tumor cells before ultrasound exposure was 4 h, for sake of sonosensitizer accumulation, i.e., protoporphyrin IX, the metabolite of 5-ALA. In vitro studies showed the higher cytotoxicity of Chemo-SDT compared to the other treatments, including i.t. CLH, intravenous (i.v.) CLH, and SDT alone. The combination of pulmonary delivery and Chemo-SDT showed the highest anticancer effect among the treatments on the metastatic lung tumor-bearing mice, which was judged according to the tumor appearance and pathological sections. The major anticancer mechanism of Chemo-SDT included the improved apoptosis of cancer cells and the enhanced production of reactive oxygen species, and more importantly, the synergy of chemotherapy and SDT. Pulmonary delivery of chemotherapeutics and sonosensitizers is a promising strategy for the treatment of lung cancer.
研究领域:
肿瘤学
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药剂学
·
治疗学
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产品关联
DOI
PubMed
高影响因子
Nanomaterials
·
2020
·Vol. 10
·期 10
·2058
·
IF 4.324
Liang Hong,Artem M. Pliss,Ye Zhan,Wenhan Zheng,Jun Xia,Liwei Liu,Junle Qu,Paras N. Prasad
Sonodynamic therapy (SDT) has emerged as an important modality for cancer treatment. SDT utilizes ultrasound excitation, which overcomes the limitations of light penetration in deep tumors, as encountered by photodynamic therapy (PDT) which uses optical excitations. A comparative study of these modalities using the same sensitizer drug can provide an assessment of their effects. However, the efficiency of SDT and PDT is low in a hypoxic tumor environment, which limits their applications. In this study, we report a hierarchical nanoformulation which contains a Food and Drug Administration (FDA) approved sensitizer chlorin, e6, and a uniquely stable high loading capacity oxygen carrier, perfluoropolyether. This oxygen carrier possesses no measurable cytotoxicity. It delivers oxygen to overcome hypoxia, and at the same time, boosts the efficiency of both SDT and PDT. Moreover, we comparatively analyzed the efficiency of SDT and PDT for tumor treatment throughout the depth of the tissue. Our study demonstrates that the strengths of PDT and SDT could be combined into a single multifunctional nanoplatform, which works well in the hypoxia environment and overcomes the limitations of each modality. The combination of deep tissue penetration by ultrasound and high spatial activation by light for selective treatment of single cells will significantly enhance the scope for therapeutic applications.Keywords:photodynamic;sonodynamic;hypoxia;nanoemulsion;delivery;tumor
研究领域:
肿瘤学
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药剂学
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生物医学工程
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DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2020
·
IF 0
Lintao Bai,Mingkun Wang,Lin Zhang,Meijun Zhao,Mei Ren,Lirong Zheng,Ming Lei,Heyun Shen
Sonodynamic therapy (SDT) has gained widespread attention owning to its much deeper tissue penetration depth compared with phototherapy. However, developing sonosensitizers with high sonosensitization efficacy in a tumor hypoxic environment is still a significant challenge. Herein, we fabricated a poly(amino acid) coordination nanoparticle (PFHF) as a potent sonosensitizer with great biocompatibility and high hydroxyl radical (•OH)-generation capacity for efficient SDT. PFHF was identified as a hexa-coordination structure by X-ray absorption fine structure and density functional theory. Furthermore, PFHF could be excited by ultrasound, which directly cleaved H2O into •OH, achieving oxygen-independent SDT. In addition, doxorubicin-loaded PFHF achieved a significant synergistic chemo-sonodynamic therapeutic effect with a tumor inhibition rate of 89%. The poly(amino acid) coordination nanoparticle with good biocompatibility and oxygen-independent ability could provide an idea for the rational design of sonosensitizers.
研究领域:
癌症治疗
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纳米技术
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超声治疗
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材料科学
✓ 已验证
产品关联
DOI
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2021
·
IF 5.875
Xuexue Liu,Kai Zhao,Jin Cao,Xueyong Qi,Lin Wu,Song Shen
Nanoparticles have been demonstrated to be effective in targeted drug delivery to tumor due to the enhanced permeability and retention (EPR) effect. However, the inhomogeneous distribution of the nanoparticles in the tumor and the slow release of the drug make the therapeutic effect unsatisfied. Here, we present reactive oxygen species (ROS)-responsive micelles comprising poly (ethylene glycol)-poly(propylene sulfide) (PEG-PPS) for targeted delivery and in situ release of drug. Upon the irradiation of ultrasound, the loaded sonosensitizer hypocrellin (HC) will generate ROS to trigger the disassembly of the micelles and meanwhile realize sonodynamic therapy (SDT) effect of cancer. The in vivo experiment indicates that the HC loaded PEG-PPS are biocompatible and much more efficacious than an equivalent amount of free HC in inhibiting the growth of cancer.
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
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
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诊疗学
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传染病学
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药学科学
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Sijia Wu,Qian Wang,Jun Du,Lejin Zhu,Fujun Yang,Jiacheng Lu,Xueyu Li,Yuhao Li,Jingtao Cui,Yuqing Miao
Sonodynamic therapy (SDT) represents a promising, noninvasive, and precise treatment modality for tumors, demonstrating significant potential in clinical applications. However, the efficiency of sonosensitizers in generating reactive oxygen species (ROS) is often limited by rapid electron-hole recombination. In this study, BiF 3 @BiOI is synthesized via a co-precipitation method, followed by in-situ reduction to decorate it with Pt nanoparticles, resulting in BiF 3 @BiOI@Pt-PVP (BBP) nanocomposite for enhancing SDT efficacy. The formation of the BiF 3 @BiOI heterojunction enhances charge separation ability. The decoration of Pt nanoparticles narrows the bandgap and alters the band positions and Fermi level of BBP, which can effectively mitigate the rapid recombination of electron-hole pairs and facilitate a cascade reaction of ROS, thereby improving ROS generation efficiency with ultrasound excitation. Additionally, bismuth ions in BBP and the generated holes consume glutathione, exacerbating cellular oxidative damage, and triggering PANoptosis and ferroptosis. Furthermore, Pt nanoparticles demonstrate peroxidase-like activity, catalyzing endogenous hydrogen peroxide to oxygen. These functions are helpful against tumors for alleviating hypoxic conditions, reshaping the microenvironment, modulating immune cell infiltration capacity, and enhancing the efficacy of immunotherapy. The dual strategy of forming heterojunctions and sensitization with noble metals effectively enhances the efficacy of sono-catalytic therapy-induced immune activation in tumor treatment.
研究领域:
肿瘤学
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生物材料学
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免疫学
✓ 已验证
DOI
高影响因子
Small
·
2022
·Vol. 18
·期 12
·2106568
·
IF 15.153
Anwei Zhou,Tianliang Fang,Kerong Chen,Yurui Xu,Zhuo Chen,Xinghai Ning
Ferroptosis is a type of nonapoptotic cell death and is gradually emerging as an important anticancer treatment. However, its therapeutic efficacy is impaired by low intracellular levels of reactive oxygen species (ROS) and long-chain polyunsaturated fatty acids, significantly limiting its therapeutic potential. Herein, a multimodal strategy to improve ferroptosis is presented, in which a state-of-art engineered erythrocyte, termed as sonodynamic amplified ferroptosis erythrocyte (SAFE), is developed for simultaneously activating ferroptosis and oxygen-riched sonodynamic therapy (SDT). SAFE is composed of internalizing RGD peptide and red blood cell membrane hybrid camouflaged nanocomplex of hemoglobin, perfluorocarbon, ferroptosis activator (dihomo-γ-linolenic acid, DGLA), and sonosensitizer verteporfin. It is identified that SAFE, under ultrasound stimulation, can not only substantially supply oxygen to overcome tumor hypoxia associated therapeutic resistance, but effectively activate ferroptosis through the coeffect of SDT triggered ROS production and DGLA mediated lipid peroxidation. In vivo studies reveal that SAFE selectively accumulates in tumor tissues and induces desirable anticancer effects under mild ultrasound stimulation. Importantly, SAFE can effectively inhibit tumor growth with minimal invasiveness, resulting in a prolonged survival period of mice. Therefore, a multimodal ferroptosis therapy driven by oxygen-riched sonodynamic peroxidation of lipids, significantly advancing synergistic cancer treatment, is presented.
研究领域:
肿瘤学
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生物医学工程
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药理学
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2025
·
IF 6.5
Wentao Xu,Jiajia Zheng,Jiaqi Zhang,Houhui Shi,Weili Peng,Yang Liu,Guodong Feng,Yuguang Wang,Yi-Jun Liang,Jun Chen
Background Liver cancer is one of the most prevalent cancers globally, with approximately 90% of primary liver cancers being hepatocellular carcinomas (HCC). However, current systemic treatment options (whether monotherapy or combination therapy) are limited and offer only modest survival benefits. The effectiveness of a drug is largely determined by its concentration at the target site. Therefore, an effective drug delivery system must enhance drug accumulation at the target site, enable selective drug release there, and facilitate escape from lysosomes.Methods cRGD-Lipo@Ce6/DOX was prepared by modifying c(RGDyK) onto the surface of drug-loaded liposomes containing Chlorin e6 (Ce6) and doxorubicin (DOX) through an amide reaction. The targeting capability and uptake mechanism of cRGD-Lipo@Ce6/DOX for HCC were analyzed using flow cytometry. To investigate drug release mechanisms and changes in subcellular distribution following ultrasound stimulation, further studies were conducted. The therapeutic efficacy and biosafety of this dual-modality therapy were then evaluated in an HCC subcutaneous tumor-bearing mouse model.Results The prepared nanocomplex exhibits a surface charge of −9.91 ± 2.94 mV and an apparent size of 118.07 ± 1.46 nm. Modification of the RGD cyclic peptide on the surface of the drug-carrying liposomes enhanced the targeting and penetration efficiency for HCC. In vitro experiments on drug uptake mechanisms and release demonstrated that reactive oxygen species (ROS) generated by sonodynamic therapy (SDT) promote effective drug release from the carrier into the non-lysosomal region. The combined SDT and chemotherapy treatment achieved a 94% tumor inhibition rate and showed excellent biosafety in HCC subcutaneous tumor-bearing mice.Conclusion Therefore, the effectiveness of the combination treatment strategy utilizing SDT in conjunction with chemotherapy provides additional treatment options for patients with HCC.
研究领域:
肿瘤学
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药剂学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Yanling Wang,Lishi Luo,Tuotuo Zhang,Jun-Rui Hu,Huiling Wang,Feng Bao,Chonglu Li,Yao Sun,Junrong Li
Sonodynamic therapy (SDT) can generate reactive oxygen species (ROS) to combat multidrug-resistant biofilms, which pose significant challenges to human health. As the key to producing ROS in SDT, the design of sonosensitizers with optimal molecular structures for sufficient ROS generation and activity in complex biofilm matrix is essential. In this study, we propose a π-expansion strategy and synthesize a series of small-molecule metal Ru(II) complexes (Ru1–Ru4) as sonosensitizers (Ru1–Ru4) to enhance the efficacy of SDT. Among these complexes, Ru4 demonstrates remarkable ROS generation capability (∼65.5-fold) that surpasses most commercial sonosensitizers (1.3- to 6.7-fold). Through catalyzing endogenous H2O2 decomposition, Ru4 facilitates the production of abundant O2 as a resource for 1O2 and the generation of new ROS (i.e., •OH) for improving SDT. Furthermore, Ru4 maintains the sustained ROS activity via consuming the interferences (e.g., glutathione) that react with ROS. Due to these unique advantages, Ru4 exhibits potent biofilm eradication ability against methicillin-resistant Staphylococcus aureus (MRSA) both in vitro and in vivo, underscoring its potential use in clinical settings. This work introduces a new approach for designing effective sonosensitizers to eliminate biofilm infections, addressing a critical need in healthcare management.
研究领域:
医学
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微生物学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Shuangyu Tian,Jinghang Li,Dongdong Wang,Yingchao Han,Honglian Dai,Lesan Yan
Sonodynamic therapy (SDT), an emerging cancer treatment with significant potential, offers the advantages of non-invasiveness and deep tissue penetrability. The method involves activating sonosensitizers with ultrasound to generate reactive oxygen species (ROS) capable of eradicating cancer cells, addressing the challenge faced by photodynamic therapy (PDT) where conventional light sources struggle to penetrate deep tissues, impacting treatment efficacy. This study addresses prevalent challenges in numerous nanodiagnostic and therapeutic agents, such as intricate synthesis, poor repeatability, low stability, and high cost, by introducing a streamlined one-step assembly method for nanoparticle preparation. Specifically, the sonosensitizer Chlorin e6 (Ce6) and the chemotherapy drug erlotinib are effortlessly combined and self-assembled under sonication, yielding carrier-free nanoparticles (EC-NPs) for non-small cell lung cancer (NSCLC) treatment. The resulting EC-NPs exhibit optimal drug loading capacity, a simplified preparation process, and robust stability both in vitro and in vivo, owing to their carrier-free characteristics. Under the synergistic treatment of sonodynamic therapy and chemotherapy, EC-NPs induce an excess of reactive oxygen in tumor tissue, prompting apoptosis of cancer cells and reducing their proliferative capacity. Both in vitro and in vivo experiments demonstrate superior therapeutic effects of EC-NPs under ultrasound conditions compared to free Ce6. In summary, our research findings highlight that the innovatively designed carrier-free sonosensitizer EC-NPs present a therapeutic option with commendable efficacy and minimal side effects.
研究领域:
肿瘤学
·
药剂学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 37
·7686-7697
·
IF 6.331
Jingmei Guo,Yue Xu,Miaodeng Liu,Jian Yu,Hongye Yang,Wenlong Lei,Cui Huang
The validity and biocompatibility of irrigating agents are imperative for the success of root canal therapy. The imperfections in the currently available irrigants highlight the fact that more advanced technologies and strategies are required for complete disinfection in endodontic treatments. In the present study, a Fenton reaction-enhanced antimicrobial sonodynamic therapy (SDT) platform was fabricated for root canal disinfection. Firstly, mesoporous silica nanoparticles (MSNs) were synthesized, grafted with an amino group and then conjugated with sonosensitizer protoporphyrin IX (PpIX). Iron ions were then anchored (M@P-Fe) to initiate a Fenton reaction. Nanoparticle characterization by size and zeta potential measurements, scanning electron microscopy, transmission electron microscopy and thermogravimetric analysis confirmed that the platform was successfully developed. Reactive oxygen species (ROS) generation assessment, methylene blue degradation and electron spin resonance assays illustrated upon ultrasound (US) irradiation, that augmented ROS, can be produced by US activated PpIX and iron mediated Fenton reactions from low concentration H2O2 (0.01%). In vitro anti-Enterococcus faecalis efficacy was demonstrated by growth curve and colony forming unit measurements. Confocal laser scanning microscopy and scanning electron microscopy observations illustrated the effectiveness of the platform on in situ biofilm eradication in root canal. Owing to the stronger oxidizing capability and short lifetime of ROS, the Fenton reaction-enhanced SDT can induce detrimental oxidative damage to bacteria upon activation of US while avoiding nonspecific toxicity to cells, which was verified by cytotoxicity evaluations using CCK-8 assay and morphology observation of MC3T3-E1 cells. Compared to commonly used NaClO, this nanoplatform displayed desirable anti-bacterial, anti-biofilm abilities and better biocompatibility. These results highlight that the integrated M@P-Fe + US + H2O2 platform is a promising candidate for US enhanced root canal irrigation and disinfection.
研究领域:
牙科学
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生物医学工程
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2020
·
IF 10.317
Yang Liu,Ying Wang,Wenyao Zhen,Yinghui Wang,Songtao Zhang,Ying Zhao,Shuyan Song,Zhijian Wu,Hongjie Zhang
Poor chemical stability, low tumor enrichment, and weak therapeutic effects of commonly used organic sonosensitizers significantly hinder further clinical applications of sonodynamic therapy (SDT). Encouraged by the principles of semiconductor catalysis and defect chemistry, we obtained a defect-rich gadolinium (Gd) doped zinc oxide (D-ZnO x :Gd) semiconductor sonosensitizer by defect engineering for efficient deep tumor sonodynamic eradication. The abundant oxygen defect can promote the separation of the electron (e − ) and hole (h + ) of D-ZnO x :Gd, which significantly enhances the sonodynamic effect. In addition, D-ZnO x :Gd is more easier to adsorb water and oxygen molecules due to its rich oxygen-deficient, greatly enhancing the capacities of ROS production. A significantly higher sonodynamic ROS generation abilities and anti-deep tumor efficiency against breast cancer are obtained in such defect-rich ZnO nanobullets. This work not only broadens the applications of ZnO semiconductor nanoagent in the field of nanomedicine , but also reveals the mechanism of how the oxygen deficiency enhanced the sonodynamic efficacy of zinc oxide , providing a new application of defect engineering in the field of cancer therapy.
研究领域:
纳米医学
·
肿瘤学
·
材料科学
✓ 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）