Nano Research
·
2020
·Vol. 13
·期 12
·3403-3415
·
IF 8.183
Zeng Fanchu,Qin Huan,Liu Liming,Chang Haocai,Chen Qun,Wu Linghua,Zhang Le,Wu Zhujun,Xing Da
Effective therapeutic strategies to precisely eradicate primary tumors with minimal side effects on normal tissue, inhibit metastases, and prevent tumor relapses, are the ultimate goals in the battle against cancer. We report a novel therapeutic strategy that combines adjuvant black phosphorus nanoparticle-based photoacoustic (PA) therapy with checkpoint-blockade immunotherapy. With the mitochondria targeting nanoparticle, PA therapy can achieve localized mechanical damage of mitochondria via PA cavitation and thus achieve precise eradication of the primary tumor. More importantly, PA therapy can generate tumor-associated antigens via the presence of the R848-containing nanoparticles as an adjuvant to promote strong antitumor immune responses. When combined with the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4, the generated immunological responses will further promote the infiltrating CD8 and CD4 T-cells to increase the CD8/Foxp3 T-cell ratio to inhibit the growth of distant tumors beyond the direct impact range of the PA therapy. Furthermore, the number of memory T cells detected in the spleen is increased, and these cells inhibit tumor recurrence. This proposed strategy offers precise eradication of the primary tumor and can induce long-term tumor-specific immunity.
研究领域:
肿瘤学
·
纳米技术
·
免疫治疗
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Journal of Oncology
·
2022
·
IF 4.501
Liping Qian,Lihua Mao,Weixing Mo,Rong Wang,Yunlong Zhang
Glioblastoma (GBM) is the most common intracranial tumor with characteristic of malignancy. Resveratrol, a natural originated polyphenolic compound, has been reported to act as a potential radiosensitizer in cancer therapy. Magnetic resonance imaging (MRI) is the first choice for the diagnosis, pathological grading, and efficacy evaluation of GBM. In this study, MRI was applied to observe whether resveratrol could intensify the anti-GBM tumor effect by enhancing antitumor immunity during radiotherapy. We established an intracranial C6 GBM model in SD rats, treated with radiation and resveratrol. The increased body weight, the inhibition on mortality, and tumor volume in radiated- GBM rats were further enhanced by resveratrol addition, while the pathological damage of brain was alleviated. The modulation of radiation on inflammation, cell cycle, and apoptosis was strengthened by resveratrol; and Ki-67, PD-L1, and cell cycle- and apoptosis-related protein expressions were also improved by cotreatment. Besides, cotreatment attenuated DNA damage and induced G0/G1-phase cell arrest of GBM rats, accompanied with the changed expression of ATM-AKT-STAT3 pathway-related proteins. Moreover, the percentages of CD3+CD8+T cells and IFN-γ+CD8+T cells were enhanced, while (CD4+CD25+Foxp3)/CD4+T cells were decreased by radiation or resveratrol, which was strengthened by cotreatment. The modulation effect of cotreatment on CD3, Foxp3, and IFN-γ levels was also stronger than radiation or resveratrol alone. To conclude, resveratrol enhanced the effect of radiotherapy by inducing DNA damage and antitumor immunity in the intracranial C6 GBM.
研究领域:
肿瘤学
·
放射学
·
免疫学
·
神经科学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2021
·
IF 9.776
Yudi Deng,Zhijie Jiang,Yincheng Jin,Jianan Qiao,Shan Yang,Hui Xiong,Jing Yao
Detrimental tumor microenvironment (TME) relies on distorted tumor vasculature for further tumor expansion. Vascular normalization therapy partly improves TME through vessel repairing, while these therapies enter an unbreakable Möbius ring due to each attempt hindered by pro-angiogenic factors from TME, leading to limited duration and extent of vascular normalization. Here, we developed a nanosystem including FLG and MAR/MPA nanodrugs to regulate both tumor vasculature and TME. FLG nanodrugs were constructed by connecting VEGF/VEGFR2 inhibitory low molecular weight heparin and gambogic acid with F3 peptide decoration for directly regulating on vascular endothelial cells and inducing vascular normalization. Meanwhile, MAR/MPA nanodrugs encapsulating CCL5/CCR5 blocker maraviroc were designed to restrict cytokine functions of angiogenesis and TME deterioration, contributing to vasculature repairing and TME reconstruction. Our results demonstrated this combined nanosystem synergistically induced vascular normalization window lasting 9 days and restored vascular permeability and oxygen supply in Panc-1 tumor. Furthermore, in melanoma, our nanosystem achieved immune improvements with increased infiltration of CD4 + and CD8 + T cells in a remodeled TME. The two nanodrugs assisting each other in terms of both vascular repairing and TME improvements successfully reversed the vicious crosstalk to a positive one, achieving overall TME remodeling and promoting therapeutic efficiency.
研究领域:
肿瘤学
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纳米技术
·
药理学
·
免疫学
·
癌症生物学
✓ 已验证
DOI
PubMed
高影响因子
eLife
·
2024
·
IF 6.4
Youxi Liu,Meimei Yin,Xiaoting Mao,Shuai Wu,Shuangping Wei,Shujun Heng,Yichun Yang,Jinwen Huang,Zhuolin Guo,Chuan Li,Chao Ji,Liu Hu,Wenjie Liu,Ling-juan Zhang
Allergic contact dermatitis (ACD), a prevalent inflammatory skin disease, is elicited upon repeated skin contact with protein-reactive chemicals through a complex and poorly characterized cellular network between immune cells and skin resident cells. Here, single-cell transcriptomic analysis of the murine hapten-elicited model of ACD reveals that upon elicitation of ACD, infiltrated CD4+ or CD8+ lymphocytes were primarily the IFNγ-producing type 1 central memory phenotype. In contrast, type 2 cytokines (IL4 and IL13) were dominantly expressed by basophils, IL17A was primarily expressed by δγ T cells, and IL1β was identified as the primary cytokine expressed by activated neutrophils/monocytes and macrophages. Furthermore, analysis of skin resident cells identified a sub-cluster of dermal fibroblasts with preadipocyte signature as a prominent target for IFNγ+ lymphocytes and dermal source for key T cell chemokines CXCL9/10. IFNγ treatment shifted dermal fibroblasts from collagen-producing to CXCL9/10-producing, which promoted T cell polarization toward the type-1 phenotype through a CXCR3-dependent mechanism. Furthermore, targeted deletion of Ifngr1 in dermal fibroblasts in mice reduced Cxcl9/10 expression, dermal infiltration of CD8+ T cell, and alleviated ACD inflammation in mice. Finally, we showed that IFNγ+ CD8+ T cells and CXCL10-producing dermal fibroblasts co-enriched in the dermis of human ACD skin. Together, our results define the cell type-specific immune responses in ACD, and recognize an indispensable role of dermal fibroblasts in shaping the development of type-1 skin inflammation through the IFNGR-CXCR3 signaling circuit during ACD pathogenesis.
研究领域:
免疫学
·
皮肤病学
·
转录组学
·
细胞生物学
✓ 已验证
DOI
高影响因子
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
·
2020
·
IF 4.873
Liu Tang,Xiao-Lei Li,Zi-Xin Deng,Yao Xiao,Ya-Hong Cheng,Jing Li,Hong Ding
Conjugated linoleic acid (CLA), commonly found in beef, lamb and dairy products, has been reported to exhibit anti-inflammatory and antipruritus effects and to inhibit the release of chemical mediators such as histamine and eicosanoid in laboratory rodents. The chief objective of the study is to assess the efficacy of CLA on atopic dermatitis (AD) in mice and to explore possible mechanisms with CLA treatments . To develop a new therapy for AD, the anti-AD potential of CLA was investigated by inducing AD-like skin lesions in mice using 2,4-dinitrofluorobenzene. We evaluated dermatitis severity; histopathological changes; serum levels of T helper (Th) cytokines (interferon-γ, interleukin-4); changes in protein expression by western blotting and immunohistochemistry staining for cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), toll like receptor 4 (TLR-4), myeloid differentiation factor 88 (MyD88), nuclear factor-κB (NF-κB) and tumor necrosis factor α (TNF-α); and production of the proinflammatory lipid mediators, such as prostaglandin E 2 and leukotriene B4 , in the skin lesions. Treatment with CLA ameliorated the development of AD-like clinical symptoms and effectively inhibited epidermal hyperplasia and infiltration of mast cells and CD4 + T cells in the AD mouse skin. Total serum immunoglobulin E levels and the expression levels of Th1/Th2 cytokines and lipid mediators in dorsal skin were dramatically suppressed by CLA. Furthermore, CLA down-regulated the expressions of COX-2, 5-LOX, TLR4, MyD88, NF-κB and TNF-α. Taken together, our findings demonstrate the potential usefulness of CLA as an anti-inflammatory dietary supplement or drug for the prevention and management of AD skin diseases by modulating the COX-2/5-LOX and TLR4/MyD88/NF-κB signaling pathways .
研究领域:
免疫学
·
药理学
·
皮肤科
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Feiyang Jin,Jing Qi,Minxia Zhu,Di Liu,Yuchan You,Gaofeng Shu,Yan Du,Jun Wang,Hui Yu,Mingchen Sun,Xiaoling Xu,Qiying Shen,Xiaoying Ying,Jiansong Ji,Yongzhong Du
A desirable cancer therapeutic strategy is supposed to have effective ability to not only exert maximum anticancer ability but also inspire antitumor immunity for preventing tumor relapse and metastasis. During this research, multifunctional upconversion nanoparticles (UCNPs) coated by ROS-responsive micelles are prepared for tumor targeting and near-infrared (NIR)-triggered photodynamic therapy (PDT)-combined synergistic effect of chemotherapy. Moreover, both PDT and chemotherapy agents could activate antitumor immunity via inducing immunogenic cell death with CD8+ and CD4+ T cells infiltrating in tumors. Through the experiments, intravenous administration of multifunctional nanocarriers with noninvasive NIR irradiation destroys the orthotopic tumors and efficiently suppresses lung metastasis in a metastatic triple-negative breast cancer model by cascade-amplifying chemo-PDT and systemic antitumor immunity. In conclusion, this study provides prospective chemo-PDT with inspired antitumor immunity for metastatic cancer treatment.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BMC Medicine
·
2022
·Vol. 20
·期 1
·1-18
·
IF 11.15
Cheng Yibin,Wang Caixia,Wang Huihui,Zhang Zhiwei,Yang Xiaopeng,Dong Yanming,Ma Lixin,Luo Jingwen
Background The application of combination therapy for cancer treatment is limited due to poor tumor-specific drug delivery and the abscopal effect. Methods Here, PD-L1- and CD44-responsive multifunctional nanoparticles were developed using a polymer complex of polyethyleneimine and oleic acid (PEI-OA) and loaded with two chemotherapeutic drugs (paclitaxel and chloroquine), an antigen (ovalbumin), an immunopotentiator (CpG), and an immune checkpoint inhibitor (anti-PD-L1 antibody). Results PEI-OA greatly improved the drug loading capacity and encapsulation efficiency of the nanoplatform, while the anti-PD-L1 antibody significantly increased its cellular uptake compared to other treatment formulations. Pharmacodynamic experiments confirmed that the anti-PD-L1 antibody can strongly inhibit primary breast cancer and increase levels of CD4+ and CD8+ T cell at the tumor site. In addition, chloroquine reversed the “immune-cold” environment and improved the anti-tumor effect of both chemotherapeutics and immune checkpoint inhibitors, while it induced strong immune memory and prevented lung metastasis. Conclusions Our strategy serves as a promising approach to the rational design of nanodelivery systems for simultaneous active targeting, autophagy inhibition, and chemotherapy that can be combined with immune-checkpoint inhibitors for enhanced breast cancer treatment.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Xiaoliang Deng,Xianquan Feng,Xiaohui Tang,Zhihui Zheng,Da Zheng,Enqin Zheng,Lingjun Zeng,Shiying Xu,Boxin Chen,Qian Zhang,Zhihong Liu,Hongtao Song
The clinical efficacy of immunotherapy in triple-negative breast cancer (TNBC) faces dual barriers: poor immunogenicity and a suppressive tumor microenvironment. While low-temperature photothermal therapy (LTPTT) has emerged as a potential immunostimulatory strategy, its efficacy is counteracted by heat shock protein (HSP) induction and COX-2/PGE2-mediated immunosuppression. To address these challenges, we developed a multifunctional immunophotothermal nanoplatform (IAC NPs) through rational engineering of human serum albumin for combinatorial delivery of indocyanine green as a photothermal converter, atovaquone for HSP70-mediated thermoresistance blockade, and celecoxib for COX-2/PGE2 pathway inhibition. The IAC NPs achieved tumor-targeted delivery and NIR-activated immunogenic phototherapy while coinhibiting HSP70 (via atovaquone’s mitochondrial complex III blockade) and the COX-2/PGE2 immunosuppressive axis (via celecoxib). The triple medications’ synergistic action improved the expression of effector memory T cells, boosted the maturation of dendritic cells, encouraged the infiltration of CD4+ and CD8+ T cells, and reduced regulatory T cells. In vivo, the IAC NPs mediated profound suppression of both primary tumors and metastatic dissemination while exhibiting optimal biocompatibility for clinical translation. Our work validates a nanoenabled self-delivery system that augments the efficacy of LTPTT immunotherapy against TNBC by orchestrating coordinated inhibition of HSPs and inflammatory responses.
研究领域:
癌症免疫治疗
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纳米医学
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光热治疗
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分子靶向治疗
·
肿瘤微环境
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-16
·
IF 10.6
Lan Zhou,Liu Wei-Jia,Yin Wu-Wei,Yang Sheng-Ren,Cui Hao,Zou Ke-Long,Cheng Guo-Wang,Chen Hao,Han Yan-Hua,Rao Lang,Tian Rui,Li Ling-Ling,Zhao Yu-Yue,Yu Guang-Tao
Photothermal therapy is favored by cancer researchers due to its advantages such as controllable initiation, direct killing and immune promotion. However, the low enrichment efficiency of photosensitizer in tumor site and the limited effect of single use limits the further development of photothermal therapy. Herein, a photo-responsive multifunctional nanosystem was designed for cancer therapy, in which myeloid-derived suppressor cell (MDSC) membrane vesicle encapsulated decitabine-loaded black phosphorous (BP) nanosheets (BP@ Decitabine @MDSCs, named BDM). The BDM demonstrated excellent biosafety and biochemical characteristics, providing a suitable microenvironment for cancer cell killing. First, the BDM achieves the ability to be highly enriched at tumor sites by inheriting the ability of MDSCs to actively target tumor microenvironment. And then, BP nanosheets achieves hyperthermia and induces mitochondrial damage by its photothermal and photodynamic properties, which enhancing anti-tumor immunity mediated by immunogenic cell death (ICD). Meanwhile, intra-tumoral release of decitabine induced G2/M cell cycle arrest, further promoting tumor cell apoptosis. In vivo, the BMD showed significant inhibition of tumor growth with down-regulation of PCNA expression and increased expression of high mobility group B1 (HMGB1), calreticulin (CRT) and caspase 3. Flow cytometry revealed significantly decreased infiltration of MDSCs and M2-macrophages along with an increased proportion of CD4+, CD8+ T cells as well as CD103+ DCs, suggesting a potentiated anti-tumor immune response. In summary, BDM realizes photothermal therapy/photodynamic therapy synergized chemotherapy for cancer.
研究领域:
癌症研究
·
纳米技术
·
免疫治疗
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2022
·
IF 9.965
Guanghui Hou,Junmin Qian,Min Guo,Weijun Xu,Jinlei Wang,Yaping Wang,Aili Suo
Immune checkpoint blockade (ICB)-based immunotherapy is a revolutionary therapeutic strategy for hepatocellular carcinoma (HCC). However, tumor immune tolerance and escape severely restrict the therapeutic efficacy of ICB therapy. It is urgent to explore new strategies to potentiate ICB therapy in HCC. Herein, we developed manganese oxide-crosslinked bovine albumin/hyaluronic acid nanoparticles (BHM) by an innovative hydrazide-manganese coordination and desolvation process. Successive loading of doxorubicin (DOX) and indocyanine green (ICG) was achieved via hydrazone linkage and electrostatic interactions, respectively, obtaining DOX/ICG-coloaded BHM nanoplatform (abbreviated as BHMDI). The BHMDI nanoplatform exhibited a high drug content (>46%) and pH/reduction dual-responsive drug release behavior. The nanoplatform could efficiently alleviate tumor hypoxia by catalytic decomposition of intracellular H 2 O 2 to O 2 and significantly improve BHMDI-based photodynamic chemotherapy efficacy. The BHMDI nanoplatform downregulated the proportion of alternatively activated (M2) macrophages in tumors and simultaneously induced immunogenic death of HCC cells, thus promoting the maturation of dendritic cells and ensuing priming of CD4 + and CD8 + T cells . Importantly, programmed death-1 (PD-1) blockade in combination with BHMDI nanoplatform not only eradicated primary tumors but inhibited tumor recurrence, abscopal tumor growth and lung metastasis of HCC by triggering robust systemic antitumor immunity. This work proved the feasibility of BHMDI-based photodynamic chemotherapy for potentiating PD-1 blockade immunotherapy by reversing hypoxic and immunosuppressive tumor microenvironment.
研究领域:
肿瘤学
·
纳米技术
·
免疫学
·
药学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2021
·
IF 8.947
Xinran Song,Yuxin Jiang,Weixing Zhang,Gomaa Elfawal,Kaili Wang,Di Jiang,Huoyan Hong,Jinglei Wu,Chuanglong He,Xiumei Mo,Hongsheng Wang
Transcutaneous immunization (TCI) has the advantages of safety, high efficiency, non-invasiveness and convenient use. The key for a TCI system is transdermal targeted delivery of antigen to dendritic cells (DCs), the most powerful antigen presenting cells . DCs also play an important role in tumor immunotherapy, which provides a huge imagination for the application of TCI to tumor treatment. In this study, a transcutaneous tumor vaccine (TTV) delivery system was developed using the electrospun silk fibroin (SF) and polyvinyl alcohol (PVA) composite nanofibrous patch loaded with mannosylated polyethyleneimine (PEI man )-modified ethosome (Eth) (termed Eth-PEI man ). Eth-PEI man showed a good performance in targeting DCs, and the carriers loaded with antigen (encapsulated in Eths) and adjuvant (absorbed in PEI man ) were observed effectively induce DCs maturation in vitro. With the tyrosinase-related protein-2 (TRP2) peptide as antigen and oligodeoxynucleotides containing unmethylated CpG motifs as adjuvant, the TTV-loaded patches (TTVP) significantly inhibited the growth of melanoma in a syngeneic mouse model for melanoma by subcutaneous injection of B16F10 cell lines. Moreover, the combined application of the TTVP and anti-programmed death-1 monoclonal antibody (aPD-1) produced a synergistic antitumor effect, which could be related to the infiltration of more CD4 + and CD8 + T cells in the tumor tissues. The application of TTVP also increased the expression of IL-12, which may be part of the mechanism of synergistic antitumor effect between the TTVP and aPD-1. These results suggest that the combination of the TTVP and immune checkpoint blockers could be an effective strategy for tumor treatment. Statement of significance Transcutaneous immunization has the advantages of safety, high efficiency, non-invasiveness and convenient use. In this study, a novel transcutaneous tumor vaccine patch (TTVP) was developed using tumor antigens-loaded ethosomes that can target dendritic cells percutaneously. Our data demonstrated that the TTVP can significantly inhibit tumor growth. Furthermore, the combination of TTVP and aPD-1 produced a synergistic anti-melanoma effect. Considering its convenience and non-invasiveness, this TTVP system could find good application prospects in immunotherapy. The combination of TTVP and aPD-1 could be a useful strategy for the prevention and treatment of tumors.
研究领域:
免疫学
·
肿瘤学
·
药学
·
生物技术
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Guanghui An,Heming Zheng,Lianshan Guo,Jingmei Huang,Congling Yang,Zhihao Bai,Nannan Wang,Wenhui Yang,Yanqiu Zhu
Tumors produce a hypoxic environment that greatly influences cancer treatment, and conventional chemotherapeutic drugs cannot selectively accumulate in the tumor region because of the lack of a tumor targeting mechanism, causing increased systemic toxicities and side effects. Hence, designing and developing new nanoplatforms that combine multimodal therapeutic regimens is essential to improve tumor therapeutic efficacy. Herein, we report the synthesis of ultrafine Cu nanoparticles loaded with a drug combination of cisplatin (Pt) and 1-methyl- d -tryptophan (1-MT) and externally coated with 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin (TCPP) photosensitizer, polydopamine (PDA) and CaO 2 of MIL-101(Fe) as a new nanoplatform (Cu@MIL-101@PMTPC). The nanoplatform synergistically combined chemodynamic therapy (CDT), photodynamic therapy (PDT), and immunochemotherapy. The Fe 3+ in MIL-101(Fe) and the surface Cu nanoparticles exhibited strong ability to consume intracellular glutathione (GSH), thereby generating a Fenton-like response in the tumor microenvironment (TME) with substantial peroxidase (POD)-like and superoxide dismutase (SOD)-like activities. In this design, we used the indoleamine 2,3-dioxygenase (IDO) inhibitor 1-MT to overcome chemotherapy-induced immune escape phenomena including enhanced CD8 + and CD4 + T cell expression, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) production, and accelerated immunogenic cell death. The targeted release of cisplatin loaded into Cu@MIL-101@PMTPC also reduced toxic side effects of chemotherapy. TCPP generated a large amount of singlet oxygen ( 1 O 2 ) upon specific laser irradiation to effectively kill tumor cells. CaO 2 on the outer layer generated oxygen (O 2 ) and hydrogen peroxide (H 2 O 2 ) to ameliorate hypoxia in the tumor microenvironment, enhance the PDT effect, and provide a continuous supply of H 2 O 2 for the Fenton-like reaction. Thus, this nanocarrier platform exhibited a powerful chemodynamic, photodynamic, and immunochemotherapeutic cascade, providing a new strategy for cancer treatment.
研究领域:
纳米技术
·
癌症治疗
·
材料科学
·
药学
·
生物医学工程
✓ 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）