Acta Pharmaceutica Sinica B
·
2022
·
IF 14.903
Lujing Geng,Tong Lu,Huaqing Jing,Yue Zhou,Xiaoyang Liang,Jiao Li,Nan Li
Ferroptosis (FPT), a novel form of programmed cell death, is characterized by overwhelming iron/reactive oxygen species (ROS)-dependent accumulation of lipid peroxidation (LPO). However, the insufficiency of endogenous iron and ROS level limited the FPT therapeutic efficacy to a large extent. To overcome this obstacle, the bromodomain-containing protein 4 (BRD 4 )-inhibitor (+)-JQ1 (JQ1) and iron-supplement ferric ammonium citrate (FAC)-loaded gold nanorods (GNRs) are encapsulated into the zeolitic imidazolate framework-8 (ZIF-8) to form matchbox-like [email protected] /ZIF-8 for the amplified FPT therapy. The existence of matchbox (ZIF-8) is stable in physiologically neutral conditions but degradable in acidic environment, which could prevent the loaded agents from prematurely reacting. Moreover, GNRs as the drug-carriers induce the photothermal therapy (PTT) effect under the irradiation of near-infrared II (NIR-II) light owing to the absorption by localized surface plasmon resonance (LSPR), while the hyperthermia also boosts the JQ1 and FAC releasing in the tumor microenvironment (TME). On one hand, the FAC-induced Fenton/Fenton-like reactions in TME can simultaneously generate iron (Fe 3+ /Fe 2+ ) and ROS to initiate the FPT treatment by LPO elevation. On the other hand, JQ1 as a small molecule inhibitor of BRD 4 protein can amplify FPT through downregulating the expression of glutathione peroxidase 4 (GPX4), thus inhibiting the ROS elimination and leading to the LPO accumulation. Both in vitro and in vivo studies reveal that this pH-sensitive nano-matchbox achieves obvious suppression of tumor growth with good biosafety and biocompatibility. As a result, our study points out a PTT combined iron-based/BRD 4 -downregulated strategy for amplified ferrotherapy which also opens the door of future exploitation of ferrotherapy systems.
研究领域:
癌症研究
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纳米技术
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治疗学
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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
Acta Biomaterialia
·
2023
·
IF 9.7
Yang Du,Xiaohui Qian,Fenghao Lin,Bingqiang Gao,Weili Wang,Huang Yang,Weilin Wang,Yuan Ding
The therapeutic effects of photothermal therapy (PTT) are dependent on the photothermal conversion efficiency of photothermal agents (PTAs) in tumors and the subsequent activation of the antitumor immune system. However, the insufficient tumor accumulation of current PTAs and the inevitable recruitment of tumor-associated macrophages (TAMs) could further compromise the antitumor activities of PTT. To address these issues, a biomimetic photothermal nanoplatform [email protected] is developed for the targeted remodeling of TAMs, which promotes the antitumor immunity of PTT. Au nanorods with second near-infrared (NIR-II) absorptions are fabricated to serve as PTAs to induce immunogenic cell death in tumor cells. The ferric hydroxide shell coated on Au nanorods can release iron ions to repolarize M2-like TAMs into the tumoricidal M1 phenotype via P38 and STAT1-mediated signaling pathways . Moreover, the surface decoration of platelet membranes endows biomimetic nanoplatform with enhanced tumor targeting ability for precise tumor ablation and TAM regulation. Consequently, [email protected] under NIR-II laser irradiation exhibits significantly higher inhibitory effects in a poor immunogenic 4T1 tumor-bearing mouse model with a 50% complete remission rate compared to conventional PTT (0%). By simultaneously reversing the immunosuppressive tumor microenvironment, this biomimetic nanoplatform offers a promising strategy for enhancing the antitumor efficacy of PTT. Statement of significance The therapeutic effects of current photothermal therapy (PTT) are hindered by the insufficient tumor accumulation of conventional photothermal agents and the recruitment of immunosuppressive tumor-associated macrophages (TAMs) after PTT. Herein, we report a biomimetic iron-based second near-infrared (NIR-II) photothermal nanoplatform ( [email protected] ) for targeted TAMs reprogramming and NIR-II mediated anti-tumor immunity. [email protected] can actively target the tumor site with the help of surface-decorated platelet membranes. Meanwhile, iron ions would be released from [email protected] in acidic lysosomes to reprogram TAMs into tumoricidal M1-like macrophages, which promotes the antitumor responses elicited by NIR-II PTT, thereby contributing to remarkable tumor inhibitory effects, with 50% higher complete remission rate than that of conventional PTT.
研究领域:
纳米技术
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癌症治疗
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免疫疗法
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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
Advanced Science
·
2023
·Vol. 10
·期 11
·2206979
·
IF 15.1
Si Zheng,Duyang Gao,Yayun Wu,Dehong Hu,Ziyue Li,Yuenan Wang,Hairong Zheng,Yingjia Li,Zonghai Sheng
Radioimmunotherapy (RIT) is an advanced physical therapy used to kill primary cancer cells and inhibit the growth of distant metastatic cancer cells. However, challenges remain because RIT generally has low efficacy and serious side effects, and its effects are difficult to monitor in vivo. This work reports that Au/Ag nanorods (NRs) enhance the effectiveness of RIT against cancer while allowing the therapeutic response to be monitored using activatable photoacoustic (PA) imaging in the second near-infrared region (NIR-II, 1000–1700 nm). The Au/Ag NRs can be etched using high-energy X-ray to release silver ions (Ag + ), which promotes dendritic cell (DC) maturation, enhances T-cell activation and infiltration, and effectively inhibits primary and distant metastatic tumor growth. The survival time of metastatic tumor-bearing mice treated with Au/Ag NR-enhanced RIT is 39 days compared with 23 days in the PBS control group. Furthermore, the surface plasmon absorption intensity at 1040 nm increases fourfold after Ag + are released from the Au/Ag NRs, allowing X-ray activatable NIR-II PA imaging to monitor the RIT response with a high signal-to-background ratio of 24.4. Au/Ag NR-based RIT has minimal side effects and shows great promise for precise cancer RIT.
研究领域:
癌症治疗
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纳米技术
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免疫学
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医学影像
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放射生物学
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Quanshi Lin,Yichao Wang,Linlin Wang,Zhijin Fan
Significant progress has been made in cancer immunotherapy; however, challenges such as interpatient variability, limited treatment response, and severe side effects persist. Although nanoimmunotherapy has emerged as a promising approach, the construction of precise and efficient nanosystems remain formidable challenges. Herein, a multifunctional nanoplatform was developed using macrophage-derived cellular vesicles (MCVs) for NIR-II imaging-guided precise cancer photo-immunotherapy. MCVs exhibited excellent tumor targeting and TAMs re-education effects, serving as both delivery carriers and therapeutic agents. Through amide bond, indocyanine green (ICG) was conjugated to the surface of MCVs, enabling in vivo tracking of MCVs distribution. Notably, ICG exhibited dual functionality as a NIR-II fluorescent agent and possessed photodynamic and photothermal effects, enabling the conversion of light energy into chemical or heat energy to eliminate tumor cells. This precision phototherapy triggered immunogenic cell death (ICD) of tumor, thereby activating the anti-tumor immune response. Additionally, MCVs loaded with R848, a toll-like receptor agonist, augmented the ICD-induced anti-tumor immunity. Animal experiments confirmed that MCVs-mediated photoimmunotherapy promoted T cell infiltration, inhibited tumor growth, and improved survival rates. In conclusion, we have developed a promising precision immunotherapy strategy capable of enhancing the immune response while mitigating off-target effects. These findings offer encouraging prospects for clinical translation.
研究领域:
癌症免疫治疗
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纳米技术
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生物医学工程
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免疫学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Weilun Pan,Bodeng Wu,Chengtao Nie,Tingting Luo,Zhenli Song,Jie Lv,Yong Tan,Chunchen Liu,Mingzhen Zhong,Tong Liao,Zhenxun Wang,Guanghui Yi,Limin Zhang,Xiaoliu Liu,Bo Li,Jinxiang Chen,Lei Zheng
Developing an effective dressing against bacterial infection and synchronously addressing wound complications, such as bleeding, long-term inflammation, and reinfection, are highly desirable in clinical practice. In this work, a second near-infrared (NIR-II) responsive nanohybrid consisting of imipenem encapsulated liposome with gold-shell and lipopolysaccharide (LPS)-targeting aptamer, namely ILGA, is constructed for bacteria elimination. Benefiting from the delicate structure, ILGA exhibits strong affinity and a reliable photothermal/antibiotic therapeutic effect toward multidrug-resistant Pseudomonas aeruginosa (MDR-PA). Furthermore, by incorporating ILGA with a thermosensitive hydrogel poly(lactic-co-glycolic acid)–polyethylene glycol–poly(lactic-co-glycolic acid) (PLGA-PEG-PLGA), a sprayable dressing ILGA@Gel was prepared, which enables a quick on-demand gelation (10 s) for wound hemostasis and offers excellent photothermal/antibiotic efficacy to sterilize the infected wound. Additionally, ILGA@Gel provides satisfactory wound-healing environments by reeducating wound-associated macrophages for inflammation alleviation and forming a gel layer to block exogenous bacterial reinfection. This biomimetic hydrogel reveals excellent bacteria eradication and wound recovery effectiveness, demonstrating its promising potential for managing complicated infected wounds.
研究领域:
生物医学工程
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纳米技术
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药学
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伤口愈合
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传染病
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2024
·
IF 18
Tian Zhang,Dongsheng Tang,Pengfei Wu,Shaoping Jiang,Yuquan Zhang,Abid Naeem,Yong Li,Chunhui Li,Bo Hu,Shuai Guo,Caixia Sun,Haihua Xiao,Ran Yan,Yuhua Weng,Yuanyu Huang
Immune checkpoint blockade (ICB) therapy is a widely favored anti-tumor treatment, but it shows limited response to non-immunogenic “cold” tumors and suffers from drug resistance. Photodynamic therapy (PDT), as a powerful localized treatment approach, can convert a “cold tumor” into a “hot tumor” by inducing immunogenic cell death (ICD) in tumor cells, thereby enhancing tumor immunogenicity and promoting tumor immunotherapy. However, the effectiveness of PDT is largely hindered by the limited penetration depth into tumor tissues. To address these issues, we proposed an all-in-one drug system with NIR-II photo-accelerated PDT effects, efficient immune checkpoint gene silencing, and a facile manufacturing process. The so-called all-in-one drug system comprises a multi-modal designed polymer PPNP and siRNA. PPNP is an amphipathic polymer that includes the near infrared-II (NIR-II) photosensitizer Aza-boron-dipyrromethene (Aza-BODIPY), a glutathione (GSH)-cleavable linker, and a cationic monomer derived from cholesterol. PPNP can self-assemble and efficiently load siRNA. Under laser irradiation, PPNP triggers a potent ICD cascade, causing the on-demand release of siPD-L1, reshaping the tumor's immunosuppressive microenvironment, effectively inhibiting the growth of various tumors, and stimulating the immune memory. This study represents a generalized platform for PDT and gene silencing, designed to modulate immune-related signaling pathways for improved anticancer therapy.
研究领域:
肿瘤学
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免疫治疗
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药理学
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生物医学工程
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CERAMICS INTERNATIONAL
·
2024
·
IF 5.1
Xiuna Tian,Youfeng Wen,Hongjian Dou,Lingyuan Wu,Changjun Wang,Youzi Zhang
In the clinical diagnosis and treatment of diseases, there is an urgent need to find suitable materials for real-time temperature monitoring of biological tissues. The paper provides a detailed study of the effects of Nd 3+ doping concentration on the negative thermal expansion performance and NIR fluorescence properties of Sc 2 (MoO 4 ) 3 . The results obtained from Rietveld refinement of in-situ XRD data indicates that high concentration of Nd 3+ doping significantly influences the negative thermal expansion performance of the material, as well as alters the temperature-dependent changes in NIR fluorescence intensity and lifetime. In addition, a NIR fluorescence lifetime temperature probe doped with Nd 3+ /Yb 3+ /Er 3+ has been constructed. When the temperature increased from 303 K to 403 K, the fluorescence intensity of the probe at 1538 nm increased by a factor of 127.5. Furthermore, as the temperature rose from 323 K to 403 K, the fluorescence lifetime of the probe at 1538 nm extended from 41.93 μs to 204 μs. By utilizing the lifetime of Er 3+ for temperature sensing, a relative sensitivity of 6.03%K −1 was achieved at 323 K, indicating significant potential application value of this probe in the field of biological temperature measurement.
研究领域:
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
INTEGRATED FERROELECTRICS
·
2023
·
IF 0.7
Lu-Ping Chen,Zhen Zhang,Wang-Quan Zhang,Hai-Lin Cong,You-Qing Shen,Bing Yu
Malignant tumor is one of the most important causes of death in the world today. At present, the successful cure cases of tumor patients are mainly due to the timely treatment of tumors. Therefore, it has become one of the urgent problems for human beings to find tumors as soon as possible and how to completely eradicate them. The technology of simultaneous imaging and treatment through photoinitiation is a promising strategy to fight cancer. In the previous research, we developed a new small molecule p-QM2AF for photothermal therapy, but the low fluorescence efficiency (QY) in the NIR-II range made it necessary to modify it. In this paper, we obtained better imaging and photothermal conversion performance by grafting two 9- methylene nonadecanes onto the p-QM2AF sub-receptor.
研究领域:
生物医学工程
·
肿瘤学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Ding Wen,Lile Dong,Kai Li,Yechao Du,Ruiping Deng,Jing Feng,Hongjie Zhang,Daguang Wang
Despite bismuth-based energy conversion nanomaterials having attracted extensive attention for nanomedicine, the nanomaterials suffer from major shortcomings including low tumor accumulation, long internal retention time, and undesirable photothermal conversion efficiency (PCE). To combat these challenges, bovine serum albumin and folic acid co-modified Bi2Se3 nanomedicine with rich selenium vacancies (abbreviated as VSe-BS) was fabricated for the second near-infrared (NIR-II) light-triggered photonic hyperthermia. More importantly, selenium vacancies on the crystal planes (0 1 5) and (0 1 11) of VSe-BS with similar formation energies could be distinctively observed via aberration-corrected scanning transmission electron microscopy images. The defect engineering endows VSe-BS with enhanced conductivity, making VSe-BS possess outstanding PCE (54.1%) in the NIR-II biowindow and desirable photoacoustic imaging performance. Tumor ablation studies indicate that VSe-BS possesses satisfactory therapeutic outcomes triggered by NIR-II light. These findings give rise to inspiration for further broadening the biological applications of defect engineering bismuth-based nanomaterials.
研究领域:
纳米医学
·
生物材料学
·
肿瘤治疗
✓ 已验证
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2022
·Vol. 32
·期 46
·2208028
·
IF 19.924
Jian He,Shiyuan Hua,Dongxiao Zhang,Kai Wang,Xiaoyuan Chen,Min Zhou
Molecular imaging-guided precision photothermal therapy has shown tremendous potential for invasively thermal ablation with solid tumors. However, it is still a pressing clinical need to develop precise and deep-tissue multi-scale imaging technologies easily integrated into a single system to boost accurate photothermal treatments. Herein, a SERS/NIR-II optical nanoprobe assembled by gold nanostars, Raman molecular tags, and silver sulfide quantum dots through silica bridges (named AuDAg 2 S) is reported that allows the combination of the fingerprint-style surface-enhanced Raman scattering (SERS) imaging and second region near-infrared (NIR-II) in-depth biological fluorescence imaging. It can also yield strong localized surface plasmon resonance for a satisfactory photothermal conversion efficiency of 67.1% at 1064 nm to effectively kill CT26 colon cancer cells. Moreover, the AuDAg 2 S nanoprobes can enhance the detection sensitivity up to the picomolar level and increase the depth of the NIR-II fluorescence signal up to 1 cm under the excitation of the near-infrared laser. As a result, the AuDAg 2 S nanoprobes can achieve multidimensional tumor imaging in levels of living subjects, histology, and single cell, and further guided deep NIR-II photothermal anti-tumor therapy in vivo. This study offers a promising approach for SERS/NIR-II whole optical imaging for deep tumor photothermal treatment in future clinical applications.
研究领域:
分子影像
·
癌症治疗
·
纳米技术
·
生物医学工程
·
光学
✓ 已验证
DOI
高影响因子
Theranostics
·
2025
·Vol. 15
·期 10
·4481
·
IF 13.3
Yupeng Sun,Rui Li,Yike Cai,Yan Liu,Peiyuan Wang,Ming Wu,Xiaolong Zhang,Naishun Liao,Cuilin Zhang,Aixian Zheng,Haipo Xu,Rui Zeng,Yongyi Zeng,Xiaolong Liu
Tumor-infiltrating CD8 + T cells and programmed death-1 (PD1) levels are critical indicators for tumor immunophenotyping and therapeutic decision-making. Noninvasive optical imaging in the second near infrared window (NIR-II) is particularly well-suited for investigating the biological processes within tumors in live mammals, thanks to its deep-tissue penetration and superior spatiotemporal resolution. However, in vivo NIR-II imaging has primarily been restricted to a single probe at a time. Methods: Herein, we developed a two-plex NIR-II molecular imaging method utilizing the non-overlapping fluorescence emission of indocyanine green (ICG) in the NIR-IIa window (1000-1200 nm) and PbS/CdS core-shell quantum dots (QDs) in the NIR-IIb window (1500-1700 nm). By integrating PD1 aptamer-labeled ICG (ICG-Apt-PD1, targeting PD1) and CD8 aptamer-labeled QDs (QDs@Apt-CD8, targeting CD8 + T cells), our two-plex NIR-II molecular imaging enabled simultaneous and noninvasive monitoring of the number of CD8 + T cells and PD1 levels in tumors. Results: QDs@Apt-CD8 demonstrated the excellent ability for in vivo imaging of tumor infiltrating CD8 + T cells, owing to its strong NIR-IIb luminescence and the high selectivity and specificity. This two-plex in vivo molecular imaging allowed for dynamic monitoring for PD1 levels and the number of CD8 + T cells in tumors. We observed the heterogeneous bio-distributions of PD1 and CD8 + T cells across different tumor types and revealed the tumor immunophenotypes. Moreover, our findings indicated that the low PD1 and high CD8 + T cells levels in tumors predicted a better anti-tumor effect. Conclusions: Such in vivo noninvasive NIR-II molecular imaging would complement ex vivo biopsy-based diagnostic techniques, and it could contribute to developing an in vivo tumor immune-scoring algorithm to offer a more precise prediction for immunotherapeutic response.
研究领域:
生物医学工程
·
肿瘤免疫学
·
分子影像学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR IMAGING AND BIOLOGY
·
2023
·Vol. 25
·期 5
·875-886
·
IF 3.1
Hui Xin,Wang Yanxing,Li Wenjing,Yuan Ying,Tao Xiaofeng,Lv Ruichan
In this research, we designed a novel NIR II luminescence imaging probe with targeting effect to accurately track oral squamous cell carcinoma (OSCC) cells. Massive gene expression data were processed by weighted gene co-expression network analysis to establish a network of relationships between genes. After clustering, correlation of clinical information, and gene functional enrichment analysis, MMP1 was predicted to be a biomarker/therapeutic target for OSCC cells. To obtain rare-earth probes with better luminescence in the NIR II region, we adjusted the doping ratio of the rare-earth element (Nd, Gd, Er, and Yb) fraction of the Nd-Mn molecular cluster to optimize its luminescence properties. The results of in vitro targeting experiments showed that Nd-Mn-MMP1Ab can target Cal-27 cells, demonstrating at the cellular level that the MMP1 gene is a biomarker for oral cancer, which also proves that the cancer targets predicted by the bioinformatics approach are correct.
研究领域:
生物信息学
·
癌症研究
·
分子影像学
✓ 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）