JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Yingying Xu,Liu Yang,Chengyan Wang,Weiming Sun,Yijing Zheng,Beiwei Ou,Lixian Wu,Leilei Shi,Xi Lin,Wei Chen
Oral cancer is a disease with high morbidity and mortality worldwide and greatly impacts the quality of life, especially in patients with advanced stages. Photodynamic therapy (PDT) is one of the most effective clinical treatments for oral cancers. However, most clinically applied photosensitizers have several deficiencies, including oxygen dependence, poor aqueous solubility, and a lack of tumor-targeting ability. Herein, the carrier-free multifunctional Sorafenib (Sor), chlorin e6 (Ce6), and Fe 3+ self-assembly co-delivery nanoparticles (Sor-Ce6 NPs) were constructed via combining a ferroptosis inducer Sor and a photosensitizer Ce6 for synergetic therapy. The as-synthesized Sor-Ce6 NPs presented excellent colloidal stability and water dispersity with good in vivo tumor-targeting ability. More significantly, the low dose of Sor-Ce6 NPs had little dark toxicity but produced significantly enhanced ROS and supplied O 2 sustainably to increase phototoxicity through ferroptosis pathway. Notably, the Sor-Ce6 NPs showed significantly higher in vitro and in vivo anti-tumor efficacy than the Sor/Ce6 mixture due to the improvement of cellular uptake and the incorporation of foreign Fe ions in the system, which also confer the T 1 magnetic resonance-guided imaging ability to the formed Sor-Ce6 NPs. Our study demonstrates a promising self-assembled strategy for overcoming hypoxia-related PDT resistance for oral cancer treatment.
研究领域:
癌症治疗
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纳米技术
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药学
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生物医学工程
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2022
·Vol. 11
·期 1
·162-169
·
IF 7.59
Ren-Jiang Kong,Xin-Yu Li,Jia-Qi Huang,Xiang Zhou,Fu-An Deng,Yan-Mei Li,Ling-Shan Liu,Shi-Ying Li,Hong Cheng
Tumor cells activate DNA repair pathways to combat the oxidative damage induced by reactive oxygen species (ROS), contributing to their resistance to photodynamic therapy (PDT). Herein, a self-delivery photodynamic sensitizer is developed to enhance oxidative damage by blocking the DNA repair pathway through poly(ADP-ribose) polymerase (PARP) inhibition. Specifically, the photodynamic sensitizer (CeOla) is constructed based on the self-assembly of the photosensitizer chlorine e6 (Ce6) and the PARP inhibitor olaparib (Ola). Of note is that carrier free CeOla has a high drug content and favorable water stability, which could be effectively internalized by tumor cells for robust PDT upon light irradiation. Moreover, CeOla could inhibit the activation of PARP, promote the upregulation of γ-H2AX and reduce the expression of Rad51, thereby blocking the DNA repair pathway to sensitize tumor cells for PDT. As a consequence, the self-delivery CeOla greatly promotes the tumor cell apoptosis and shows a high antitumor performance with low side effects. It serves as a novel platform for the development of self-delivery nanomedicine to overcome oxidative resistance in tumor treatment.
研究领域:
肿瘤学
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药理学
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纳米医学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Yuping Zhao,Yanna Zhao,Qisan Ma,Bin Sun,Qingpeng Wang,Zhuang Ding,Huaizhen Zhang,Xiuling Chu,Min Liu,Zhengping Wang,Jun Han
Background The combination of chemo-photodynamic therapy based on nano-technology has emerged as a preferable and promising measure for synergetic antitumor therapy.Purpose The aim of this study was expected to overcome most of the safety concerns from nano-carriers and improve the chemo-photodynamic synergistic antitumor efficacy.Methods Herein, we reported a facile and effective approach based on the self-assembly of chemotherapeutic agent 10-hydroxycamptothecin (HCPT) and photosensitizer chlorin e6 (Ce6) for preparing stably dual-functional nanorods (NRs).Results The chemical thermodynamic parameters obtained from isothermal titration calorimeter (ITC) and the microcosmic configuration snapshots acquired by molecular dynamics (MD) simulations verified that HCPT and Ce6 molecules tended to assemble with each other through various intermolecular forces. The as-prepared HCPT/Ce6 NRs possessed a relatively uniform size of around 165 nm and zeta potential of about −29 mV, together with good stability in aqueous solution and freeze-dried state. In addition, both the extra- and intracellular reactive oxygen species (ROS) generation capacity of the NRs under laser irradiation was significantly enhanced compared with Ce6 injections. Moreover, the dual-functional HCPT/Ce6 NRs exhibited a substantial in vitro/in vivo synergistic antitumor efficacy under laser irradiation due to the integration of the two therapeutic modalities into one drug delivery system. Besides, no obvious hepatic or renal toxicity was observed in the NRs treatment groups.Conclusion Taken together, HCPT/Ce6 NRs demonstrated a powerful efficacy in chemo-photodynamic therapy for breast cancer. Therefore, the carrier-free dual-functional NRs prepared in a facile and effective strategy might give inspiration for the development of combined antitumor therapy.
研究领域:
纳米技术
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药学
·
肿瘤学
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2022
·
IF 6.14
Weicai Wang,Xiaozu Chen,Junwei Li,Qiu Jin,Hyung Jong Jin,Xuemei Li
Nanotechnology provides more developments and challenges for cancer immunotherapy. Nanomaterial-mediated synergistic therapy, immunosuppressive adjustment of the tumor microenvironment (TME), and nanovaccine construction can promote cancer immunotherapy. Here, based on the biodegradable hollow manganese dioxide (H-MnO2) tumor-targeted drug delivery platform, we have developed a TME-responsive nanovaccine for synergistic cancer therapy. The nanoplatform significantly enhanced photodynamic therapy (PDT)-mediated immune response by improving the hypoxic tumor microenvironment and on-demand drug release. At the same time, it was supplemented with gene therapy and chemotherapy to achieve significant in vivo combined therapy benefits. Taking full advantage of the high reactivity to the hydrogen peroxide and weak acidity of the TME, H-MnO2 loaded with chemotherapy drug doxorubicin (DOX) and photosensitizer chlorin e6 (Ce6) not only provided the required oxygen for photodynamic therapy but also reduced the side effects of chemotherapy drugs on normal tissues. Moreover, the coating of nucleic acid on H-MnO2 solved the problem of biocompatibility of nanoparticles and ensured that they could be swallowed by cancer cells. The results revealed that through the controlled release of targeted drugs and combined therapy, the synergistic nanovaccine significantly inhibited tumor growth in mice, which is expected to achieve the treatment of primary tumors.
研究领域:
纳米技术
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癌症免疫治疗
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药物递送系统
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光动力疗法
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基因治疗
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化疗
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生物相容性
✓ 已验证
DOI
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
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纳米技术
·
癌症治疗
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2018
·Vol. 10
·期 20
·9707-9719
·
IF 7.233
Jia Zhou,Tianliang Li,Chunlei Zhang,Junyuan Xiao,Daxiang Cui,Yingsheng Cheng
Multifunctional nanoplatforms have been developed into advanced drug delivery systems for cancer therapy. In this study, we report a charge-switchable nanocapsule with multistage pH-responsive behaviors. First, DOX-encapsulated and oleylamine-embedded hollow structures with a diameter of 132 ± 21 nm are prepared via the double emulsion method. Subsequently, the hollow structures are encompassed by Gd-DTPA-, chlorin e6 (Ce6)-, and folate (FA)-modified BSA to form tumour-targeted, dual NIR/MR imaging-guided and chemo–photodynamic therapeutic nanoplatforms. Importantly, the nanocapsule can intelligently switch its surface charge to positive under mildly acidic conditions (pH 6.5) with no release of Ce6 and DOX, which is confirmed by ξ-potential and cumulative release measurements. Moreover, confocal imaging pictures demonstrate that acid-sensitive DOX sealed in nanocapsules is progressively released into the nuclei of MGC-803 cells. These advantages as well as FA-targeting facilitate effective endocytosis and synergistic therapeutic efficacy. Selective tumour accumulation and long tumour retention time are further indicated by NIR/MR in vivo imaging. In addition, excellent therapeutic efficacy combined with chemotherapy (DOX) and photodynamic therapy (PDT) is observed with the tumour eventually ablating at the 15th day. All results demonstrate that the as-prepared nanocapsules hold great potential for clinical cancer theranostics.
研究领域:
癌症治疗
·
药物递送系统
·
纳米技术
·
成像技术
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Omega
·
2019
·
IF 2.584
Jiang Ni,Ying Sun,Jinfang Song,Yiqing Zhao,Qiufang Gao,Xia Li
Recent studies have identified photodynamic therapy (PDT) as a promising approach for cancer treatment. Here, in this study, we have constructed cancer cell membrane (CCM)-coated silica nanoparticles (SIL) as an artificial cell carrier (CCM/SIL) to effectively deliver chlorin e6 (Ce6), a commonly adopted photodynamic reagent (CCM/SIL/Ce6), to achieve enhanced PDT of cancer. In addition, apart from the generally recognized cytotoxicity induced by reactive oxygen species (ROS), our study also revealed that ROS could further potentiate the loss of intercellular junctions and integrity disruption as a result of down-regulation of VE-cadherin and CD31. Consequently, dendritic cells (DCs) were more readily accumulated to the tumor tissue and became maturated, which secreted tumor necrosis factor-α and interleukin-12 (IL-12) to trigger the following immune responses. Our work not only explored the anticancer feasibility of a new system but also demonstrated the underlining mechanisms responsible for PDT-induced anticancer effects, which offers a new perspective to employ and improve the efficacy of PDT and related systems.
研究领域:
肿瘤学
·
纳米技术
·
免疫治疗
·
光动力疗法
✓ 已验证
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
·
材料科学
·
纳米技术
·
癌症研究
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医学影像
✓ 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）