BIOMATERIALS
·
2019
·
IF 10.273
Lu Lu,Xiaojing Zhao,Tiwei Fu,Ke Li,Ye He,Zhong Luo,Liangliang Dai,Rui Zeng,Kaiyong Cai
Various obstacles impede the chemotherapy efficiency of glioma in clinic, such as blood brain barrier (BBB) and blood brain tumor barrier (BBTB). Ligand-mediated polymeric micelles have shown great potential for improving the efficiency of glioma treatment. Herein, we developed a disulfide bond-conjugated prodrug polymer consisted of camptothecin (CPT) and polyethylene glycol (PEG) with further modification of iRGD peptide. The polymer of CPT-S-S-PEG-COOH could self-assemble into nanosized polymeric micelles with diameter around 100 nm, and loaded with photosensitizer IR780 for combination therapy. The micelles displayed good stability with controlled drug release under physiological environment. Importantly, the iRGD modified polymeric micelles demonstrated favorable ability to cross the BBB and target glioma cells via αv β integrin and neuropilin-1-mediated ligand transportation in vitro and in vivo . The whole synthesis process is simple and the drug loading content of CPT in the [email protected] micelles was higher than 10%. Moreover, [email protected] micelles combined chemotherapy with photodynamic therapy (PDT) displayed more excellent tumor-killing capability than the other groups. Thus, both in vitro and in vivo studies suggested that the targeting prodrug system could not only effectively cross various barriers to reach at glioma site, but also significantly enhance the antitumor effect with laser irradiation . Our findings consequently suggested that [email protected] micelles with laser irradiation are a promising drug delivery system for glioma therapy.
研究领域:
药学
·
纳米技术
·
神经肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Applied Materials Today
·
2023
·
IF 8.3
Wei Meng,Lian-Ying Zhang,Xiao-Tong Chen,Feng-Jun Ge,Peng Huang,Yong-Jian Chen,Ting Huang,Nai-Han Huang,Yi-Ming Zou,Wen-Hua Zhang,Qun Zhang,Jin-Xiang Chen
The drug-resistant bacterial infection has seriously threatened human health and thus it is urgent to develop new and effective drugs to overcome the antibiotic resistance crisis. Herein, a near-infrared-II (NIR-II) region light-responsive Pd rough nanoshells on metal-organic framework (MOF) of UiO-66-NH 2 (UiO-66-NH 2 @Pd shell ) has been developed for the first time, which was further loaded with the photosensitizer IR780 to ultimately yield UiO-66-NH 2 @Pd shell -IR780 (UPI) as the core-shell theranostic nanoplatform. The Pd rough nanoshells demonstrate promising photothermal conversion efficiency, superoxide dismutase (SOD)-like activity, and light-enhanced catalase (CAT)-like activity. In the non-healing wound inflammatory microenvironment with overexpression of reactive oxygen species (ROS) caused by subcutaneous bacterial infection, Pd rough nanoshells in UPI transforms ROS, such as O 2 •− , into H 2 O 2 and efficiently catalyzes the decomposition of the formed and endogenous H 2 O 2 to produce O 2 . The O 2 production process could be enhanced by NIR-II light to facilitate photodynamic efficacy of IR780 to prime rapid clearance of methicillin-resistant Staphylococcus aureus (MRSA) through biofilm inhibition, along with down-regulation of hypoxia inducible factor-1α (HIF-1α) and relief of inflammation, thus promote wound healing. Moreover, UPI exhibits negligible biotoxicity in vitro and in vivo . This work provides a method for preparing promising Pd-based nanomaterials toward subcutaneous infection treatment and wound healing.
研究领域:
纳米技术
·
生物医学工程
·
光疗
·
感染性疾病
·
伤口愈合
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Chaonan Shi,Minglong Chen,Xiaodie Li,Yanping Fu,Dan Yang,Ting Wen,Wanchen Zhao,Ying Sun,Wenhao Wang,Chao Lu,Qiaoli Wu,Chuanbin Wu,Xin Pan,Guilan Quan
Immunogenic cell death (ICD) is associated with the release of damage-associated molecular patterns, including ATP, to promote an effective immune cycle against tumors. However, tumors have evolved an effective strategy for degrading extracellular immunostimulatory ATP via the ATP-adenosine axis, allowing the sequential action of the ectonucleotidases CD39 to degrade accumulated immunostimulatory ATP into pleiotropic immunosuppressive adenosine. Here, an ingenious dissolving microneedle patch (DMNs) is designed for the intralesional delivery of CD39 inhibitor (sodium polyoxotungstate, POM-1) and ICD inducer (IR780) co-encapsulated solid lipid nanoparticles (P/I SLNs) for antitumor therapy. Upon insertion into the tumor site, IR780 induces ICD modalities with the release of damage-associated molecular patterns from endogenous tissues, which activates the antitumor immune cycle. Simultaneously, POM-1 promotes the liberation of immunostimulatory ATP and lowers the level of immunosuppressive extracellular adenosine, which supported immune control of tumors via recruiting CD39-expressing immune cells. In vivo antitumor studies prove that this platform can effectively eliminate mice melanoma (tumor growth inhibitory rate of 96.5%) and colorectal adenocarcinoma (tumor growth inhibitory rate of 93.5%). Our results shed light on the immunological aspects of combinatorial phototherapy and ATP-adenosine regulation, which will broaden the scope of synergistic antitumor immunotherapy .
研究领域:
癌症免疫疗法
·
药学
·
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
Advanced Therapeutics
·
2024
·Vol. 7
·期 8
·2400045
·
IF 3.7
Shanshan Wang,Zhiqiang Bi,Tianming Lu,Ruoning Qian,Jie Yu,Qiang Zhang,Hao Yang,Wenli Lu,Yuanyuan Guo,Xiaoqing Xin,Yong Bian,Ruogu Qi
Colorectal cancer (CRC) stands out as one of the most prevalent gastrointestinal cancers. Current treatment strategies for CRC are significantly hindered by systemic toxicity and suboptimal therapeutic efficacy. This study aims to overcome these limitations by developing a robust tumor-targeting chemo-photothermal strategy, combining Bortezomib (BTZ) as a proteasome inhibitor, IR780 iodide as a near-infrared dye, and Photothermal Therapy (PTT) agent, with hyaluronic acid (HA) serving as the shell for tumor targeting, denoted as HA/PB@IR780. The investigations reveal the impressive tumor-targeting affinity of HA/PB@IR780, leading to a synergistic chemo-photothermal therapeutic effect both in vitro and in vivo. Additionally, this material demonstrates the capability for drug release triggered by low pH conditions. Moreover, HA/PB@IR780 induced the generation of reactive oxygen species (ROS), triggered cells apoptosis via the PERK-CHOP-Bcl-2 pathway, and induced Immunogenic Cell Death (ICD) in CT26 cells. Importantly, HA/PB@IR780 selectively targets tumor sites, mitigating systemic toxic side effects and significantly extending the survival of CT26 tumor-bearing mice. In conclusion, this designed tumor-targeting nanocarrier represents a promising and potentially effective platform for the precise treatment of CRC.
研究领域:
肿瘤学
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纳米技术
·
药理学
·
细胞生物学
·
治疗学
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Oncology
·
2021
·
IF 6.244
Li Ke,Li Ruyue,Zhou Baona,Chen Jing,Lan Kai,Zhan Wenhua,Chen Di,Zhang Tao,Li Xueping
Triple-negative breast cancer (TNBC) has inadequate treatment approaches and a poor prognosis. It is urgent to develop new treatment approaches for TNBC. The combination of photothermal therapy (PTT) and chemotherapy is a very effective potential therapy for TNBC. However, asynchronous accumulation, unclear efficacy, and toxic side effects hinder the further promotion of this method. Therefore, we designed and constructed a new type of nanocarriers, the cascade release near-infrared imaging (NIFI) & thermal-chemo combination nanoparticles (CNC NPs), that can release drugs through the cascade of ultrasound triggering and pH responding to achieve the synchronous tumor accumulation, monitoring and synergistic treatment of two functional molecules. The key material of CNC NPs is the polydopamine (PDA), which, through self-assembling, forms a rigid shell that contains doxorubicin (DOX) and NIF fluorescent dye IR780 on the surface of the perfluorohexane (PFH) microbubbles. The results show that CNC NPs have a hollow core-shell structure with an average particle size of 97.3 ± 27.2 nm and have exceptional colloidal stability and photothermal conversion efficiency. The NPs can effectively perform cascade drug release through ultrasound triggering and pH responding. CNC NPs have good in vivo biological safety and excellent fluorescence imaging, drug delivery, and therapeutic abilities in the TNBC models. These results provide an experimental basis for the development of new clinical treatment methods for TNBC.
研究领域:
肿瘤学
·
纳米技术
·
诊疗学
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生物医学工程
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2023
·
IF 5.9
Na Tu,Xue Shen,Shengqi Deng,Yuxin Xie,Haowei Liu,Hongping Li,Nan Li,Ling Mei
In the past decade, tumor treatment strategies have shifted from tumors to the immune system of tumor patients. NIR laser-induced photothermal therapy can not only generate heat or reactive oxygen species to kill tumors but also induce immunogenic cell death and activate the overall antitumor immune response. The ICD process is usually accompanied by autophagosome formation, which contains tumor-associated antigens. However, the fusion of autophagosome and lysosome impairs antigens, weakening the antitumor immune response. Thus, administration with autophagy terminal inhibitors could be a compensatory strategy. In this work, we prepared a thermally sensitive liposome drug delivery system containing the photothermal agent IR780 and autophagy inhibitor HCQ (IR780/HCQ-Lip). IR780/HCQ-Lip has a uniform particle size distribution and good photodynamic and photothermal properties. The inhibition of autophagy enhanced the phototherapy effect. Compared with the survival rate of 4T1 cells being treated with IR780-Lip phototherapy alone (36.87%), the survival rate of the IR780/HCQ-Lip group decreased to 3.71%. IR780/HCQ-Lip caused a massive accumulation of autophagosomes, promoted the maturation of dendritic cells (DCs), and enhanced the infiltration of intratumoral T cells. In addition, IR780/HCQ-Lip produced a systemic immune response and also showed good inhibition of distal tumor growth under laser action in distal tumor experiments. Thus, IR780/HCQ-Lip exhibited a promising combination therapy for the treatment of breast cancer.
研究领域:
肿瘤学
·
免疫疗法
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
Nanoscale
·
2021
·Vol. 13
·期 35
·14713-14722
·
IF 7.79
Xiaoshan Fan,Lingjie Ke,Hongwei Cheng,Hu Chen,Zhiguo Li,Enyi Ye,Xian-Jun Loh,Yun-Long Wu,Gang Liu,Zibiao Li
Efficient drug delivery, multifunctional combined therapy and real-time diagnosis are the main hallmarks in the exploitation of precision nanomedicine. Herein, an anthracene-functionalized micelle containing a magnetic resonance imaging (MRI) contrast agent, upconversion nanoparticles (UCNPs) and the photosensitizer IR780 is designed to achieve sustained drug release and enhanced photothermal and photodynamic therapy. The polymer-coated hybrid micelle was achieved by crosslinking anthracene-dimer with UV light (λ > 300 nm), which is converted from near-infrared (NIR) irradiation upon UCNPs. Besides, the water-insoluble photosensitizer IR780 is introduced into the system to achieve efficient drug delivery and photothermal and photodynamic synergistic therapy. As a consequence of NIR-induced anthracene-dimer formation, the cross-linked nanocomposite shows sustained drug release, and the enhanced retention effect of IR780 could increase the photothermal conversion efficiency. Importantly, the incorporation of 2,2,6,6-tetramethyl-piperidineoxyl (TEMPO) as a nitroxide MRI contrast agent presents the potential for real-time diagnosis via nanotheranostics, and the fluorescence imaging of IR780 is applied to monitor drug distribution and metabolism. This strategy of sustained drug delivery by anthracene-dimer formation through the better penetration depth of NIR-II fluorescence provides an executable platform to achieve enhanced phototherapy in biomedical applications.
研究领域:
纳米医学
·
生物医学工程
·
诊疗学
·
药物递送系统
·
光疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2023
·
IF 6.7
Peng Chen,Zeng Xiaodie,Cai Jiali,Huang Hanyu,Yang Fang,Jin Shaowen,Guan Xiuhong,Wang Zhiyong
Triple-negative breast cancer is a highly aggressive and metastatic tumor; diagnosing it in the early stages is still difficult, and the prognosis for conventional radio-chemotherapy and immunotreatment is not promising due to cancer’s immunosuppressive microenvironment. The utilization of protein-based nanosystem has proven to be effective in delivering agents with limited adverse effects, yet the combination of diagnosis and treatment remains a difficult challenge. This research took advantage of natural albumin and organic molecules to construct a self-assemble core-shell nanostructure combining with superparamagnetic iron oxide nanocrystals and heptamethine cyanine dye IR780 through non-covalent interactions. This nanocomposite successfully decreased the transverse relaxation time of the magnetic resonance hydrogen nucleus, resulting in outstanding T2 imaging, as well as emitting near-infrared II fluorescence, thereby the resulting dual-modality imaging tool was applied to improve diagnostic competency. It is noteworthy that the nanocomposites exhibited impressive enzyme-like catalytic and photothermal capabilities, resulting in a successful activation of the immune system to efficiently suppress distant metastatic lesions in vivo. Consequently, this nanodrug-based therapy could be an advantageous asset in reinforcing the immune system and hindering the growth and reappearance of the immune-cold breast cancer.
研究领域:
癌症生物学
·
纳米技术
·
成像科学
·
治疗学
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Ming Gong,Yufeng Huang,Huixiong Feng,Jiaming Lin,Anfei Huang,Jinxin Hu,Qinglian Tang,Xiaojun Zhu,Shisong Han,Jinchang Lu,Jin Wang
Treatments for osteosarcoma (OS) with pulmonary metastases reach a bottleneck with a survival rate of 10–20%. The suppressive tumor associated macrophages(TAMs) and CD47 over-expression greatly lead to the treatment failure. Sonodynamic therapy (SDT) can generate ROS with deep tumor penetration to induce tumor cell apoptosis , which is reported to further induce M1 macrophage polarization. CD47 inhibition combined with SDT to synergistically modulate TAMs may induce superior effects for OS treatment. In this work, for the first time, a biomimetic nanodrug named MPIRx was deveploped by loading IR780 (a sonosensitizer) and RRx-001 (a CD47 inhibitor) in PEG-PCL nanomicelles and then coating with OS cell membranes . After ultrasound activation, the nanodrug significantly inhibited OS proliferation and migration, induced apoptosis and immunogenic cell death in OS cells. Furthermore, MPIRx could guide macrophage migrating towards tumor cells and promote M1-type polarization while increasing the phagocytosis activity of macrophages on OS cells. Ultimately, MPIRx showed good tumor accumulation in vivo and successfully inhibited subcutaneous OS and orthotopic tumor with deterioration of pulmonary metastasis. Overall, by creating a local oxidative microenvironment and modulating the TAMs/CD47 in tumor tissue, the MPIRx nanodrug presents a novel strategy for macrophage-related immunotherapy to successfully eliminate OS and inhibit the intractable pulmonary metastasis.
研究领域:
肿瘤学
·
药学
·
免疫治疗
·
纳米技术
·
癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Di Chuan,Rangrang Fan,Bo Chen,Yangmei Ren,Min Mu,Haifeng Chen,Bingwen Zou,Haohao Dong,Aiping Tong,Gang Guo
In developing countries, the incidence of colorectal cancer (CRC) is on the rise. The combination of programmed cell death ligand-1 (PD-L1) siRNA (siPD-L1) and mild photothermal therapy (PTT) is a promising strategy for CRC treatment. In this study, dopamine-modified polyethylenimine (PEI) was prepared to fabricate an IR780 and siPD-L1 codelivery lipid–polymer hybrid nanoparticle (lip@PSD-siP) for the photothermal immunotherapy of CRC. The modification of dopamine can significantly reduce the cytotoxicity of PEI. lip@PSD-siP can be effectively taken up by CT26 cells and successfully escaped from lysosomes after entering the cells for 4 h. After CT26 cells were transfected with lip@PSD-siP, the PD-L1 positive cell rate decreased by 82.4%, and its PD-L1 knockdown effect was significantly stronger than the positive control Lipo3000-siP. In vivo studies showed that lip@PSD-siP-mediated mild PTT and efficient PD-L1 knockdown exhibited primary and distal tumor inhibition, metastasis delay, and rechallenged tumor inhibition. The treatment with lip@PSD-siP significantly promoted the maturation of dendritic cells in lymph nodes. The amount of T cell infiltration in the tumor tissues increased significantly, and the frequency of CD8+ T cells and CD4+ T cells was significantly higher than that of other groups. The percentage of immunosuppressive regulatory cells (Tregs) in the tumor tissue on the treatment side decreased by 88% compared to the PBS group, and the proportion of CD8+CD69+ T cells in the distal tumor tissue was 2.8 times that of the PBS group. The memory T cells of mice in the long-term antitumor model were analyzed. The results showed that after treatment with lip@PSD-siP, the frequency of effector memory T cells (Tem cells) significantly increased, suggesting the formation of immune memory.
研究领域:
癌症研究
·
纳米技术
·
免疫学
·
分子生物学
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2021
·Vol. 13
·期 30
·12966-12978
·
IF 7.79
Jie Yu,Xidong He,Zigui Wang,Yupeng Wang,Sha Liu,Xiaoyuan Li,Yubin Huang
Immune checkpoint blockade (ICB) therapy in combination with immunogenic death (ICD) triggered by photothermal therapy (PTT) and oxaliplatin (OXA) treatment was expected to elicit both innate and adaptive immune responses for tumor control and metastasis prevention. In this study, a photothermal agent (IR780), a folic acid (FA) linked oxaliplatin (OXA) prodrug, and PD-L1 inhibitors (BMS-1) were integrated into a liposomal system. The FA tumor-targeting and enhanced permeability and retention (EPR) effect of the liposomal system prolonged circulating times and increased accumulation in tumors, resulting in an enhanced photothermal effect and less systemic toxicity. In addition, PTT and OXA had a considerable synergistic effect in the induction of a combined ICD. The PD-1/PD-L1 checkpoint, which is a negative immune regulatory mechanism, could be blocked by the thermosensitive released BMS-1. Finally, ICD was harnessed to synergize with a small molecule PD-L1 inhibitor for activation of the immune system in the treatment of tumor relapse and metastasis.
研究领域:
癌症治疗
·
免疫学
·
纳米技术
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2023
·
IF 5.9
Yue Wu,Na Liu,Xiao-Xia Ren,Wen-Chao Zhang,Jing Qian
Combination therapy could significantly improve the therapeutic effect of tumors. However, due to the lack of reasonable integration of different treatment modes, it is difficult to maximize the effect of combination treatment. To solve this problem, by adjusting the dosage of NH4F/NaOH, we developed NaTmF4:0.5%Er3+@NaLuF4 upconversion nanoparticles with strong near-infrared luminescence. On this basis, nanocarriers (USFH-CI) encapsulated with high-loading (33.35%) Fe(acac)3, wrapped by human serum albumin, and grafted with cinnamic aldehyde (CA) and the IR780 photosensitizer were constructed. The dense extracellular matrix (ECM) in tumor tissues prevented the drug from diffusing into the tumors. Once USFH-CI nanocarriers were delivered to the tumor area, CA pH-responsively released H2O2, which promoted photothermal therapy (PTT) and photodynamic therapy (PDT) of IR780 driven by upconversion luminescence. A large number of reactive oxygen species (ROS) were generated, which led to the disintegration of the ECM and penetration into the tumors. Then, abundant Fe3+ consumed GSH to generate ample GSSG and Fe2+, which enhanced the sensitivity of tumor cells to oxidative stress, thus leading to the accumulation of lipid peroxide (LPO) and finally inducing ferroptosis. At the same time, substantial H2O2 and Fe2+ triggered off the Fenton-like reaction, releasing affluent free radicals. Beyond that, PTT of IR780 further promoted the Fenton-like reaction, and the generation of ROS was amplified. Free radicals generated in the process of ferroptosis destroyed heat shock protein produced by PTT, which solved the self-protection of cancer cells against heat. In situ ROS generation by the PTT/PDT of IR780 and the Fe2+ Fenton-like reaction further promoted the accumulation of LPO and ferroptosis as well as deep penetration, which maximized the effect of combination treatment and achieved a high tumor inhibition rate (84.71%). Also, there was negligible damage to normal tissues with good tumor targeting and digestive metabolism.
研究领域:
纳米技术
·
癌症治疗
·
材料科学
·
生物医学工程
·
光化学
·
药学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）