ACS Biomaterials Science & Engineering
·
2023
·
IF 5.8
Jun Ma,Cuixia Wen,Meng Chen,Wei Zhang,Lifeng Wang,Haitao Yin
This study fabricates a nanoparticle delivery system of gold nanoparticles–dextran nanoparticles loaded with hypoxia-activated paclitaxel dimeric prodrug nanoparticles (PTX2-NP) and photosensitizer chlorin e6/paclitaxel-nanoparticle/gold@N-(2-hydroxypropyl) (Ce6/PTX2-NP/G@NHs) and analyzed the possible molecular mechanism for enhancing the radiosensitivity of non-small cell lung cancer (NSCLC). Ce6/PTX2-NP/G@NHs were prepared by a coupling reaction and dextran inclusion, followed by characterization using spectroscopy techniques. The cellular uptake and cytotoxicity of Ce6/PTX2-NP/G@NHs were analyzed. Radiosensitizing effects of the nanoparticles were evaluated by determining the malignant phenotypes and reactive oxygen species production of A549 cells and PI3K/AKT pathway-related proteins under 685 nm laser irradiation. A549 tumor-bearing nude mice were modeled to further confirm the radiosensitizing effect. Ce6/PTX2-NP/G@NHs were effectively internalized by A549 cells, producing cytotoxicity under laser irradiation. Ce6/PTX2-NP/G@NHs reduced cell viability, clonogenic potential, migration, and invasion along with reactive oxygen species (ROS) production while promoting apoptosis in A549 cells under laser irradiation. By inhibiting the PI3K/AKT pathway, Ce6/PTX2-NP/G@NHs increased the sensitivity of A549 cells to radiotherapy where apoptotic body (ApoBD)-mediated neighboring effects also played a key role. Ce6/PTX2-NP/G@NHs accumulated in tumor sites of nude mice and enhanced the radiosensitivity of NSCLC. Ce6/PTX2-NP/G@NHs showed no obvious toxicity or side effects in vivo. Collectively, the new Ce6/PTX2-NP/G@NHs nanoparticle delivery system can enhance the radiosensitivity of NSCLC via the promotion of ApoBD-mediated neighboring effects and inactivation of the PI3K/AKT pathway.
研究领域:
肿瘤学
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药学
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纳米技术
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分子生物学
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放射生物学
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-23
·
IF 10.6
Li Haiqiu,Dou Yichen,Yang Hang,Xing Hanlin,Zhu Cheng,Wang Tao,Xuan Zhaopeng,Yang Mingxi
Background Despite the higher sensitivity of melanoma towards ferroptosis and photodynamic therapy (PDT), the lack of efficient ferroptosis inducers and the poor solubility of photosensitizers restrict their synergistic strategies. With unique advantages, carbon dots (CDs) are expected to serve as innovative building blocks for combination therapy of cancers. Results Herein, an ferroptosis/PDT integrated nanoplatform for melanoma therapy is constructed based on chlorin e6-modified Fe ions-doped carbon dots (Fe-CDs@Ce6). As a novel type of iron-carbon hybrid nanoparticles, the as-prepared Fe-CDs can selectively activate ferroptosis, prevent angiogenesis and inhibit the migration of mouse skin melanoma cells (B16), but have no toxicity to normal cells. The nano-conjugated structures facilitate not only the aqueous dispersibility of Ce6, but also the self-accumulation ability of Fe-CDs@Ce6 within melanoma area without requiring extra targets. Moreover, the therapeutic effects of Fe-CDs@Ce6 are synergistically enhanced due to the increased GSH depletion by PDT and the elevated singlet oxygen ( 1 O 2 ) production efficiency by Fe-CDs. When combined with laser irradiation, the tumor growth can be significantly suppressed by Fe-CDs@Ce6 through cyclic administration. The T 2 -weighted magnetic resonance imaging (MRI) capability of Fe-CDs@Ce6 also reveals their potentials for cancer diagnosis and navigation therapy. Conclusions Our findings indicate the multifunctionality of Fe-CDs@Ce6 in effectively combining ferroptosis/PDT therapy, tumor targeting and MRI imaging, which enables Fe-CDs@Ce6 to become promising biocompatible nanoplatform for the treatment of melanoma. Graphic Abstract
研究领域:
纳米技术
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癌症治疗
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生物医学工程
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材料科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2019
·Vol. 12
·期 3
·1801-1810
·
IF 6.97
Yang Gao,Luyun Zhang,Yanhong Liu,Sijia Sun,Zhibin Yin,Lili Zhang,Aiguo Li,Guangming Lu,Aiguo Wu,Leyong Zeng
Black titanium dioxide (TiO2) nanoparticles have attracted great attention due to their application in photothermal therapy (PTT). However, single-mode phototherapy has the risk of recurrence, and the high-dose laser usually imposed to improve the PTT performance can bring a potential threat to security. Here, polydopamine (PDA)-coated black TiO2 (b-P25@PDA) nanoparticles with a core–shell structure were synthesized for enhanced PTT; then, synergistic phototherapy nanoprobes (b-P25@PDA-Ce6 (Mn)) were constructed by coupling chlorin e6 (Ce6) and chelating Mn2+ for simultaneous photodynamic therapy (PDT)/PTT and magnetic resonance (MR) imaging, in which a low-dose laser was used and imaging-guided phototherapy with high efficiency and high safety was achieved. The prepared nanoprobes showed high photothermal conversion efficiency (32.12%), high reactive oxygen generation and excellent MR imaging. In the 4T1 tumor-bearing nude mouse model, the tumors completely disappeared under the combination of PDT/PTT with a low-dose laser but were only partially inhibited by single PDT and single PTT. The current work developed a multifunctional black TiO2-based nanoprobe for enhanced synergistic PDT/PTT and MR imaging, which will be important for the safe and efficient visualized theranostics of cancers.
研究领域:
纳米技术
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癌症治疗
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生物医学工程
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材料科学
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医学成像
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2023
·Vol. 11
·期 6
·2243-2252
·
IF 6.6
Anni Cui,Ying Bao,Haitao Xu,Xin Mu,Xiahua Zhong,Wynn Wee,Fanqi Wu,Guiye Shan
The rapid emergence of drug-resistant bacteria has attracted great attention to exploring advanced antibacterial methods. However, single-modal antibacterial therapy cannot easily eliminate drug-resistant bacteria completely due to its low efficacy. Therefore, it is essential to achieve multi-modal antibacterial therapy effectively. Herein, a dual-modal ROS generator was designed based on photosensitive PDA–MnO2@Ce6/liposome (PMCL) nanozymes for synergistic chemo-photodynamic therapy. PMCL nanozymes adhere to bacteria through liposome–membrane fusion. Meanwhile, PMCL catalyzes endogenous hydrogen peroxide (H2O2) to generate hydroxyl radicals (˙OH) and singlet oxygen (1O2) under laser irradiation. Furthermore, the photothermal effect can accelerate the generation of ROS. Based on dual-enzyme activities (mimicking peroxidase and catalase) and photodynamic properties, PMCL achieves powerful antibacterial efficacy and mature bacterial biofilm eradication. With the synergistic chemo-photodynamic effects, bacterial populations decrease by >99.76% against Gram-positive S. aureus and Gram-negative E. coli. Notably, the synergistic antibacterial properties of PMCL nanozymes are further explored using a mouse wound model of S. aureus infection. This work fabricated an efficient dual-modal ROS generator to kill bacteria, further providing a new strategy for treating wound infection.
研究领域:
生物医学工程
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纳米技术
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抗菌治疗
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材料科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-13
·
IF 10.6
Lian Jingge,Li Meng,Duan Meng,Sun Yaqian,Wang Zilin,Guo Xinyu,Li Jingchao,Gao Guo,Li Kangan
Adoptive cellular immunotherapy as a promising and alternative cancer therapy platform is critical for future clinical applications. Natural killer (NK) cells have attracted attention as an important type of innate immune regulatory cells that can rapidly kill multiple adjacent cancer cells. However, these cells are significantly less effective in treating solid tumors than in treating hematological tumors. Herein, we report the synthesis of a Fe3O4-PEG-CD56/Avastin@Ce6 nanoprobe labeled with NK-92 cells that can be used for adoptive cellular immunotherapy, photodynamic therapy and dual-modality imaging-based in vivo fate tracking. The labeled NK-92 cells specifically target the tumor cells, which increases the amount of cancer cell apoptosis in vitro. Furthermore, the in vivo results indicate that the labeled NK-92 cells can be used for tumor magnetic resonance imaging and fluorescence imaging, adoptive cellular immunotherapy, and photodynamic therapy after tail vein injection. These data show that the developed multifunctional nanostructure is a promising platform for efficient innate immunotherapy, photodynamic treatment and noninvasive therapeutic evaluation of breast cancer.
研究领域:
癌症治疗
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免疫学
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纳米技术
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医学成像
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2024
·
IF 4.9
Yue Wang,Yaning Li,Meiwen Cao,Zeyu Yan,Fenggang Wei,Tianhao Ma,Ruochen Xie,Hongchao Ma
Tumor hypoxia, limited H 2 O 2 levels, and abundant glutathione (GSH) in the tumor microenvironment (TME) pose challenges for high-efficiency reactive oxygen species (ROS)-mediated therapies. To address these limitations, an intelligent ROS-mediated nanoplatform, Ce6@ZIF-8/PDA/CuO 2 /HA (CZPCH), with photodynamic activity, self-supplied H 2 O 2 , Fenton-like reaction, GSH-depletion and photothermal activity was designed for efficient tumor treatment. In the acidic TME, CuO 2 in CZPCH deposits into Cu 2+ and H 2 O 2 , consuming GSH and triggering Fenton-like reactions to generate hydroxyl radical (•OH), enabling efficient chemodynamic therapy (CDT). Moreover, the presence of Ce6 and PDA enables CZPCH to exhibit excellent singlet oxygen ( 1 O 2 ) and temperature increase performance 660 nm and 808 nm laser irradiation, respectively, resulting in efficient photodynamic therapy (PDT) and photothermal therapy (PTT) efficacy. Interestingly, the temperature increase from PTT significantly enhances •OH and 1 O 2 generation, achieving high-efficiency ROS-based therapeutic efficacy. This synergistic CDT/PDT/PTT treatment demonstrates excellent anti-tumor efficacy and illuminates novel ROS-based therapeutic strategy design.
研究领域:
纳米技术
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癌症治疗
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生物医学工程
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材料科学
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产品关联
DOI
高影响因子
Theranostics
·
2020
·
IF 8.579
Chaoli Wang,Peng Chen,Youbei Qiao,Yuan Kang,Chaoren Yan,Zhe Yu,Jian Wang,Xin He,Hong Wu
Background : Biofilm infection caused by multidrug-resistant bacteria is difficult to eradicate by conventional therapies. Photodynamic therapy (PDT) is an effective antibacterial method for fighting against biofilm infection. However, the blocked photosensitizers outside of biofilm greatly limit the efficacy of PDT. Methods : Herein, a novel acid-responsive superporogen and photosensitizer (SiO 2 -P Ce6-IL ) was developed. Because of the protonation of the photosensitizer and the high binding energy of the polyionic liquid, SiO 2 -P Ce6-IL changed to positive SiO 2 -P IL + in an acidic microenvironment of biofilm infection. SiO 2 -P IL + could combine with negatively charged extracellular polymeric substances (EPS) and create holes to remove the biofilm barrier. To strengthen the interaction between SiO 2 -P IL + and EPS, SiO 2 -P IL + of high charge density was prepared by grafting the high-density initiation site of ATRP onto the surface of the SiO 2 base. Results : Due to the rapid protonation rate of COO - and the strong binding energy of SiO 2 -P IL + with EPS, SiO 2 -P Ce6-IL could release 90% of Ce6 in 10 s. With the stronger electrostatic and hydrophobic interaction of SiO 2 -P IL + with EPS, the surface potential, hydrophobicity, adhesion and mechanical strength of biofilm were changed, and holes in the biofilm were created in 10 min. Combining with the release of photosensitizers and the porous structure of the biofilm, Ce6 was efficiently concentrated in the biofilm. The in vitro and in vivo antibacterial experiments proved that SiO 2 -P Ce6-IL dramatically improved the PDT efficacy against MRSA biofilm infection. Conclusion : These findings suggest that SiO 2 -P Ce6-IL could rapidly increase the concentration of photosensitizer in biofilm and it is an effective therapy for combating biofilm infection.
研究领域:
材料科学
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纳米技术
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生物医学工程
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微生物学
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药学
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Liang Yu,Mingzu Zhang,Jinlin He,Xingwei Sun,Peihong Ni
ABSTRACT Anticancer drugs used for systemic chemotherapy often exhibit off-target toxicity and uncontrolled drug release due to their lack of targeting. To improve the bioavailability of drugs and reduce side effects, we have developed a mixed micelle of nanomedicine composed of two prodrugs with surface modified monoclonal antibody for cancer therapy. In this system, Nimotuzumab was used as targeting ligands of the mixed micelles (named as DCMMs) that is composed of polymer-doxorubicin prodrug (abbreviated as PEG- b -P(GMA- ss -DOX)) and maleimide polyethylene glycol-chlorin e6 (abbreviated as Mal-PEG-Ce6). The mixed micelles modified with Nimotuzumab (named as NTZ-DCMMs) bind to overexpressed EGFR receptors on Hepatoma-22 (H22) cells. Disulfide bonds in PEG- b -P(GMA- ss -DOX) are disrupted in tumor microenvironment, inducing the reduction-responsive release of DOX and leading to tumor cell apoptosis. Simultaneously, Chlorin e6 (Ce6) produced plenty of singlet oxygen ( 1 O 2 ) under laser irradiation to kill tumor cells. In vivo biological distribution and antineoplastic effect experiments demonstrate that NTZ-DCMMs enhanced drug enrichment at tumor sites through targeting function of antibody, dramatically suppressing tumor growth and mitigating cardiotoxicity of drugs. All results prove that NTZ-DCMMs have the ability to actively target H22 cells and quickly respond to tumor microenvironment, which is expected to become an intelligent and multifunctional drug delivery carrier for efficient chemotherapy and photodynamic therapy of hepatoma. Statement of significance Anticancer drugs used for systemic chemotherapy often exhibit off-target toxicity due to their lack of targeting. Therefore, it's necessary to develop effective, targeted, and collaborative treatment strategies. We construct a mixed micelle of nanomedicine based on two polymer prodrugs and modified with monoclonal antibody on surface for cancer therapy. Under the tumor cell microenvironment, the disulfide bonds of polymer- ss -DOX were broken, effectively triggering DOX release. The photosensitizer Ce6 could generate a large amount of ROS under light, which synergistically promotes tumor cell apoptosis. By coupling antibodies to the hydrophilic segments of polymer micelles, drugs can be specifically delivered. Compared with monotherapy, the combination of chemotherapy and photodynamic therapy can significantly enhance the therapeutic effect of liver cancer.
研究领域:
药学
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纳米技术
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癌症研究
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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
Nanoscale
·
2019
·Vol. 11
·期 39
·18426-18435
·
IF 6.97
Meng Duan,Fangfang Xia,Tianliang Li,Joseph G. Shapter,Sheng Yang,Yongying Li,Guo Gao,Daxiang Cui
This work explored the application of matrix metalloproteinase 2-targeted superparamagnetic nanoprobes for magnetic resonance imaging (MRI), near infrared (NIR) fluorescence imaging and photodynamic therapy of tumors. PEG, PAMAM (G5) and matrix metalloproteinase 2 (MMP2) were attached to the surface of carboxylated Fe3O4 nanoparticles (NPs) using a chemical coupling method and then finally loaded with the photosensitizer chlorin e6 (Ce6). In vitro and in vivo experiments demonstrated that the Fe3O4-PEG-G5-MMP2@Ce6 nanoprobes exhibited excellent stability, precise tumor targeting and biocompatibility. Furthermore, the fluorescence properties of Fe3O4-PEG-G5-MMP2@Ce6 nanoprobes were analogous to Ce6 and could be employed for fluorescence imaging. Meanwhile, the Fe3O4-PEG-G5-MMP2@Ce6 nanoprobes have also been shown to be effective as contrast agents for T2-weighted MRI. The target molecule MMP2 enhanced the tumor targeting ability of Fe3O4-PEG-G5-MMP2@Ce6 nanoprobes. Additionally, the Fe3O4-PEG-G5-MMP2@Ce6 nanoprobes significantly inhibited tumor growth compared with PBS and free Ce6. This work will inspire greater enthusiasm for the construction of multifunctional magnetic nanoplatforms for biomedical applications.
研究领域:
生物医学工程
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材料科学
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纳米技术
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癌症研究
·
医学影像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2025
·
IF 6.5
Binrui Shi,Mingjie Li,Renjie Feng,Guihua Wang,Liyong Deng,Yueyong Li,Kezhen Wang,Meng Du,Zhiyi Chen
Purpose: Melanoma, a highly aggressive superficial malignancy with rising incidence and mortality, faces limited sonodynamic therapy (SDT) efficacy due to poor sonosensitizer accumulation and penetration. To overcome this, we employed chlorin e6 (Ce6), a high-ROS-yield sonosensitizer, and enhanced its tumor delivery using a synergistic microneedle (MN) and ultrasound (US) strategy.Methods: Using melanoma as an application scenario, a “stepwise drug delivery” system was developed. It consisted of dissolving MN encapsulating US-responsive nanoparticles (Ce6-PFP@PLGA, CPP) and termed CPP@MN. CPP@MN breaks through the stratum corneum to deliver CPP to tumors, followed by US-triggered cavitation that mediates perfluoropentane (PFP) phase transition to enhance the tumor-penetrating capability of chlorin e6 (Ce6). Delivery efficacy was validated using three experimental models: an in vitro agarose skin phantom, ex vivo pig skin, and in vivo tumors. Furthermore, the anti-tumor efficacy of US-combined CPP@MN was evaluated at the cellular level and in tumor-bearing mice.Results: According to the results, CPP@MN showed excellent transdermal performance, including rapid dissolution of sonosensitizer and sufficient mechanical strength. MN combined with US increased the tumor penetration depth of loading drug by 2.5– 4 times across all experimental models. Ultrasonic cavitation promotes nanoparticle-derived Ce6 release and deeper tumor diffusion, resulting in specific anti-tumor efficacy.Conclusion: This innovative “stepwise drug delivery” system addresses persistent challenges in superficial tumor SDT, including inadequate sonosensitizer aggregation and poor tissue penetration, while establishing a multifunctional platform for spatiotemporally controlled drug release that sequentially overcomes the skin biological barriers.
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产品关联
DOI
PubMed
高影响因子
Materials Today Nano
·
2025
·
IF 8.2
Xinyu Mao,Shiwei Liu,Xinhao Li,Menghui Zhang,Peng Shen,Yaning Zhu,Xiaozhong Yang
Colorectal cancer (CRC) is the third most prevalent malignancy globally. Its tumor microenvironment (TME) heterogeneity and chemotherapy resistance compromise the efficacy of conventional treatments such as surgery and chemotherapy. This study developed a multifunctional nanotherapeutic platform by synthesizing mesoporous silica nanoparticles (MSNs) via a modified Stöber method. The carboxylated MSN surface was sequentially loaded with metformin (Me), chlorin e6 (Ce6), and glucose oxidase (GO X ), constructing an Me/Ce6@MSN-GO X (MCMG) nanosystem. The synthesized MSNs demonstrated excellent porosity, pore volume, and high loading capacity. In vitro and in vivo studies showed that MCMG reversed the Warburg effect via the AMPK/ACC/mTOR axis, reprogrammed tumor energy metabolism, and enhanced GO X -induced starvation therapy and Ce6-based photodynamic therapy (PDT). MCMG also alleviated TME hypoxia by suppressing HIF-1α expression, inducing an approximately 2-fold increase in intracellular reactive oxygen species levels and culminating in a 71% tumor inhibition rate in vivo. This platform integrated Me’s metabolic regulation with Ce6-mediated PDT and GO X -driven starvation therapy to achieve synergistic CRC eradication. MCMG enables multifunctional theranostics through synergistic mechanisms (metabolic modulation, oxidative damage, and nutrient deprivation) coupled with fluorescence imaging capabilities, presenting a novel strategy for CRC treatment.
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高影响因子
ACS Applied Nano Materials
·
2023
·
IF 5.9
Weiwei Zhang,Xiaokuo Shen,Wanzhen Li,Jun Wang,Zhao Kuang,Lin Gui,Yugui Tao,Ping Song,Fei Ge,Longbao Zhu
Drug-resistant bacterial infection is one of the major threats to human health. Multidrug-resistant (MDR) bacteria do not respond satisfactorily to conventional antibiotic treatment. Based on the photothermal effect, molybdenum disulfide (MoS2) nanoparticles, photosensitizer chlorin-e6 (Ce6), and an ionic liquid (IL) were used to construct a multifunctional nanoplatform (MoS2-Ce6-IL), which is responsive to near-infrared light (880 nm) and visible light (660 nm) with combined photothermal and photodynamic bacteriostatic activity. The characterization experiments revealed that the nanoplatform is spherical, with a ζ potential of −14.4 ± 1.1 mV, an overall particle size of about 230 nm, and a photothermal conversion efficiency of 54%. In this study, the treatment regimen was more than 93% effective against MDR Escherichia coli (E. coli) and more than 91% effective against Staphylococcus aureus (S. aureus). It can effectively inhibit MDR bacteria and promote skin wound healing in mice infected with S. aureus. By destroying the bacterial cell membrane and DNA, the nanoplatform interferes with the metabolism of substances and energy in bacterial cells and ultimately causes the death of MDR bacteria. In this study, a multifunctional nanosystem with remarkable bacteriostatic activity was successfully synthesized. The molecular mechanism of multidrug resistance in bacteria was elucidated, laying the foundation for its clinical application.
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高影响因子
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