Acta Biomaterialia
·
2024
·
IF 9.4
Kunlin Li,Lin Li,Xiyue Xie,Jing Zhu,Daqing Xia,Lunli Xiang,Kaiyong Cai,Jixi Zhang
Although immunogenic cell death (ICD) induced by lysosomal membrane permeabilization (LMP) evidently enhance the effectiveness of antitumor immunity for triple-negative breast cancer (TNBC) with poor immunogenicity, their potential is increasingly restricted by the development of other death pathways and the repair of lysosomes by endoplasmic reticulum (ER) during LMP induction. Herein, a polydopamine nanocomposite with i-motif DNA modified and BNN6 loaded is prepared toward boosting LMP and immunotherapy of TNBC by synergy of spatially confined photoacoustic (PA) effects and nitric oxide. Combining the high-frequency pulsed laser (4000 kHz) with the intra-lysosomal assembly of nanocomposites produced spatially confined and significantly boosted PA effects (4.8-fold higher than the individually dispersed particles extracellular), suppressing damage to other cellular components and selectively reducing lysosomal integrity to 19.2%. Simultaneously, the releasing of nitric oxide inhibited the repair of lysosomes by ER stress, causing exacerbated LMP. Consequently, efficient immune activation was achieved, including the abundant releasing of CRT/HMGB1 (5.93–6.8-fold), the increasing maturation of dendritic cells (3.41-fold), and the fostered recruitment of CD4 + /CD8 + T cells (3.99–3.78-fold) in vivo. The study paves a new avenue for the rational design and synergy of confined energy conversion and responsive nanostructures to achieve the treatment of low immunogenicity tumors. Statement of Significance A strategy of boosting lysosomal membrane permeabilization (LMP) and concomitantly preventing the repair was developed to address the immunotherapy challenge of triple-negative breast cancer. Spatially confined and significantly enhanced photoacoustic (PA) effects were achieved through DNA-guided pH-responsive assembly of polydopamine nanocomposites in lysosomes and application of a high-frequency pulsed laser. Efficient immunogenic cell death was guaranteed by selective and powerful damage of lysosomal membranes through the significant contrast of PA intensities for dispersed/assembled particles and nitric oxide release induced endoplasmic reticulum stress. The study paves a new avenue for the rational design and synergy of confined energy conversion and responsive nanostructures to achieve the treatment of low immunogenicity tumors.
研究领域:
癌症生物学
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纳米技术
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免疫治疗
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生物医学工程
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光声成像
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Jiabin Zhang,Kai Wang,Shiyao Xu,Linlin Chen,Haiquan Gu,Yujie Yang,Qi Zhao,Yurou Huo,Bo Li,Yufei Wang,Yubiao Xie,Nan Li,Jiali Zhang,Jianxu Zhang,Qianxue Li
Vaccines are widely regarded as one of the most effective weapons in the fight against infectious diseases. Currently, vaccines must be stored and transported at low temperatures as high temperatures can lead to a loss of vaccine conformation and reduced therapeutic efficacy. Metal–organic frameworks (MOFs), such as zeolitic imidazole framework-8 (ZIF-8), are a new class of hybrid materials with large specific surface areas, high loading rates, and good biocompatibility and are successful systems for vaccine delivery and protection. Silk fibroin (SF) has a good biocompatibility and thermal stability. In this study, the hepatitis B surface antigen (HBsAg) was successfully encapsulated in ZIF-8 to form HBsAg@ZIF-8 (HZ) using a one-step shake and one-pot shake method. Subsequently, the SF coating modifies HZ through hydrophobic interactions to form HBsAg/SF@ZIF-8 (HSZ), which enhanced the thermal stability and immunogenicity of HBsAg. Compared to free HBsAg, HZ and HSZ improved the thermostability of HBsAg, promoted the antigen uptake and lysosomal escape, stimulated dendritic cell maturation and cytokine secretion, formed an antigen reservoir to promote antibody production, and activated CD4+ T and CD8+ T cells to enhance memory T-cell production. Importantly, HSZ induced a strong immune response even after 14 days of storage at 25 °C. Furthermore, the nanoparticles prepared by the one-step shake method exhibited superior properties compared to those prepared by the one-pot shake method. This study highlights the importance of SF-coated ZIF-8, which holds promise for investigating thermostable vaccines and breaking the vaccine cold chain.
研究领域:
药学
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纳米技术
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免疫学
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疫苗开发
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DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Lu Wang,Chenyang Ye,Xiangjie Xue,Mingjun Xie,Yicheng Zhi,Xiao Feng,Pengcheng Zhao,Jichun Zhou,Mi Mi,Jinrui Li,Qinhao Gu,Ye Zhao,Jiaxin Chen,Yi Zhou,Yanan Xue,Zexin Fu,Liuyi Zhou,Lulu Chen,Lei Pan,Yi Sun,Linbo Wang,Sufan Wu,Yong He,Ji Wang
Breast reconstruction is essential for improving the appearance of patients after cancer surgery. Traditional breast prostheses are not appropriate for those undergoing partial resections and cannot detect and treat locoregional recurrence. Personalized shape prostheses that can smartly sense tumor relapse and deliver therapeutics are needed. A 3D-printed prosthesis that contains a therapeutic hydrogel is developed. The hydrogel, which is fabricated by crosslinking the polyvinyl alcohol with N1 -(4-boronobenzyl)- N3 -(4-boronophenyl)- N1 , N1 , N3 , N3 -tetramethylpropane-1,3-diaminium, is responsive to reactive oxygen species (ROS) in the tumor microenvironment. Specifically, RSL3, a ferroptosis inducer that is loaded in hydrogels, can trigger tumor ferroptosis. Intriguingly, RSL3 encapsulated in the ROS-responsive hydrogel exerts antitumor effects by increasing the numbers of tumor-infiltrated CD4+ T cells, CD8+ T cells, and M1 macrophages while reducing the number of M2 macrophages. Therefore, this new prosthesis not only allows personalized shape reconstruction, but also detects and inhibits tumor recurrence. This combination of aesthetic appearance and therapeutic function can be very beneficial for breast cancer patients undergoing surgery.
研究领域:
生物医学工程
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癌症研究
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组织工程
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药物递送系统
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免疫疗法
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2023
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IF 11.2
Panpan Song,Bingjie Wang,Qi Pan,Tianze Jiang,Xiangyan Chen,Miao Zhang,Jiaojiao Tao,Xia Zhao
Programmed cell death-ligand 1 (PD-L1) small interfering RNA (siRNA) achieves tumor immunotherapy by restoring the immune response of T cells, but the efficacy of PD-1/PD-L1 monotherapy is relatively low. While immunogenic cell death (ICD) can improve the response of most tumors to anti-PD-L1 and enhance tumor immunotherapy. Herein, a targeting peptide GE11-functionalized dual-responsive carboxymethyl chitosan (CMCS) micelle (G-CMssOA) is developed for simultaneous delivery of PD-L1 siRNA and doxorubicin (DOX) in a complex form of DOX·PD-L1 siRNA (D&P). The complex-loaded micelles (G-CMssOA/D&P) have good physiological stability and pH/reduction responsiveness, and improve the intratumoral infiltration of CD4 + and CD8 + T cells, reduce Tregs (TGF-β), and increase the secretion of immune-stimulatory cytokine (TNF-α). The combination of DOX-induced ICD and PD-L1 siRNA-mediated immune escape inhibition significantly improves anti-tumor immune response and inhibits tumor growth. This complex delivery strategy provides a new approach for effectively delivering siRNA and enhancing anti-tumor immunotherapy.
研究领域:
药学
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免疫学
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癌症研究
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Lanhong Su,Yuhao Hao,Rui Li,Wen Pan,Xiaopeng Ma,Jianping Weng,Yuanzeng Min
Immune checkpoint blockade (ICB) therapy has shown promising antitumor effects, but its immune response rate remains unsatisfactory. In recent years, chemotherapy has been proven to have synergistic effects with ICB therapy because some chemotherapeutic agents can enhance the immunogenicity of tumor cells by inducing immunogenic cell death (ICD). However, it cannot be ignored that chemotherapy often shows limited therapeutic efficacy due to high cytotoxicity, drug resistance, and some other side effects. Herein, we report a strategy to improve cancer immunotherapy by utilizing red blood cell-based vaccines (RBC-vaccines) where chemotherapy-induced tumor antigens (cAgs) are anchored onto red blood cells (RBCs) via the EDC/NHS-mediated amine coupling reaction. In this work, RBC-vaccines administered subcutaneously are primarily devoured by dendritic cells (DCs) and significantly improve the efficacy of αPD-1 (anti-programmed cell death 1) treatment by increasing the infiltration of intratumoral CD8 + and CD4 + T cells and elevating the intratumoral ratio of CD8 + T cells to regulatory T cells in the CT-26 colon cancer model. Finally, based on the rejection of tumor rechallenge in cured mice, the combination therapy of RBC-vaccines and αPD-1 can induce the expansion of memory T cells and thereby establish a long-term antitumor immune response. Taken together, the proposed RBC-vaccines have great potential to improve chemoimmunotherapy. Statement of significance Immunotherapy, especially immune checkpoint blockade therapy, has made great contributions to the treatment of some advanced cancers. Unfortunately, the great majority of patients with cancer do not benefit from immunotherapy. To enhance the response rate of immunotherapy, we developed red blood cell-based vaccines (RBC-vaccines) against cancers where antigens were harvested from chemotherapy-treated cancer cells and then attached to erythrocytes via covalent surface modification. Such RBC-vaccines could provide a wide variety of tumor antigens and damage-associated molecular patterns without the use of any extra ingredients to trigger a stronger antitumor immune response. More importantly, the combination of RBC-vaccines with PD-1 blockade could significantly improve the efficacy of cancer immunotherapy and induce durable antitumor immunity.
研究领域:
肿瘤学
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免疫治疗
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癌症生物学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Proteomics Clinical Applications
·
2022
·Vol. 16
·期 6
·2100099
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IF 3.603
Ting Li,Hong Qu,Haibo Ding,Haiteng Deng,Yuling Chen
Purpose Antiretroviral therapy (ART) prevents human immunodeficiency virus (HIV)-1 onward transmission and disease progression, leading to excellent prognosis in people living with HIV-1 (PWH). However, side effects, complications, and impaired immune reconstitution persist in some patients treated with ART. We aimed to profile proteome changes in plasma before and after ART to identify the molecular pathways altered by ART. Experimental Design Quantitative proteomics analysis based on tandem mass tag (TMT) labeling was used to profile proteome changes of paired plasma samples from HIV-1 patients before receiving ART and after ART treatment. Results A total of 1398 protein groups (PGs) were identified, in which 18 proteins were downregulated and 50 were upregulated in plasma from ART treated patients. Based on Ingenuity Pathway analysis (IPA), gap junction signaling and actin cytoskeleton signaling were enriched among upregulated proteins, while downregulated proteins were mainly participated in IL-15 signaling pathway. Patients with the low level of CSF1R and the high levels of MINPP1 and TGM3 showed better CD4 + T-cell recovery. Conclusions The present study provided plasma proteome changes after ART to elucidate the underlying mechanistic pathways in response to ART, and also identified potential targets to prompt immune reconstitution.
研究领域:
免疫学
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蛋白质组学
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病毒学
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临床研究
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产品关联
DOI
PubMed
高影响因子
DALTON TRANSACTIONS
·
2022
·Vol. 52
·期 1
·147-158
·
IF 4.569
Linming Li,Ming Zhang,Dianlong Jia,Zhifang Liu,Ning Zhang,Bin Sun,Zhengping Wang,Min Liu,Qingpeng Wang
To develop new chemotherapeutics with anti-metastasis properties, a series of multi-specific niflumic acid (NFA) platinum(IV) complexes with DNA damage, inflammation inhibition, immunity activation, and angiogenesis suppression mechanisms were designed, synthesized and evaluated as novel antitumor agents. The dual NFA platinum(IV) complex with a cisplatin core showed promising antitumor activities both in vitro and in vivo with lower toxicity than platinum(II) drugs and displayed attractive anti-metastasis performance. It caused serious DNA damage and further elevated the expression of γ-H2AX. Furthermore, it promoted apoptosis by activating the mitochondrial apoptotic pathway and autophagy of tumor cells. Moreover, immune response in tumors was significantly improved by increasing CD3+, CD4+ and CD8+ T infiltrating cells. Subsequently, the pathway ERK/HIF-1α/VEGFA associated with angiogenesis was suppressed by the reduced inflammation and elevated immune response, and the density of microvessels marked by CD34 was significantly reduced in tumors. Accordingly, the multi-specific NFA platinum(IV) complexes have great potential to be developed as novel anti-proliferative and anti-metastatic drugs.
研究领域:
肿瘤学
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药理学
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分子生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2024
·
IF 5.6
Chengchen Pang,Bei Yuan,Keyun Ren,Haitao Xu,Kunying Nie,Chunlei Yu,Zhanli Liu,Yanyan Zhang,Sibel A. Ozkan,Qingqing Yang
In preparing monoclonal antibodies by hybridoma cell technology, the quality of B lymphocytes used for cell fusion directly affects the sensitivity of monoclonal antibodies. To obtain B-lymphocytes producing high-quality specific antibodies for cell fusion during the immunization phase of the antigen, we prepared a TH2-Cell stimulatory delivery system as a novel adjuvant. Astragalus polysaccharide has a good ability to enhance antigenic immune response, and it was encapsulated in biocompatible materials PLGA as an immunostimulatory factor to form the delivery system (APS-PLGA). The preparation conditions of APSP were optimized using RSM to attain the highest utilization of APS. Immunization against ZEN-BSA antigen using APSP as an adjuvant to obtain B lymphocytes producing ZEN-specific antibodies for cell fusion. As results present, APSP could induce a stronger TH2 immune response through differentiating CD4 T cells and promoting IL-4 and IL-6 cytokines. Moreover, it could slow down the release efficiency of ZEN-BSA and enhance the targeting of ZEN-BSA to lymph nodes in vivo experiments. Ultimately, the sensitivity of mouse serum ZEN-specific antibodies was enhanced upon completion of immunization, indicating a significant upregulation of high-quality B lymphocyte expression. In the preparation of monoclonal antibodies, the proportion of positive wells for the first screening was 60%, and the inhibition rates of the antibodies were all similar (>50%). Then we obtained the ZEN monoclonal antibody with IC50 of 0.049 ng/mL, which was more sensitive than most antibodies prepared under conventional adjuvants. Finally, a TRFIAS strip assay was preliminarily established with a LOD value of 0.246 ng/mL.
研究领域:
免疫学
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生物技术
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纳米技术
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ORAL PATHOLOGY & MEDICINE
·
2021
·Vol. 51
·期 1
·74-85
·
IF 4.253
Jing-Ya Yang,Fang Wang,Gang Zhou
Background Oral lichen planus (OLP) is a T-cell-mediated chronic inflammatory disease with uncertain aetiology. Mucosal-associated invariant T (MAIT) cells and γδT cells are unconventional, innate-like T cells with immunoregulatory capacity. This study aimed to investigate the potential effects of MAIT and γδT cells on the pathogenesis of OLP. Methods Circulating MAIT cells and γδT cells were identified using flow cytometry. Surface proteins including CD4, CD8, CD69, CD103, CD49d, programmed death-1 (PD-1) and its ligand PD-L1 were assessed. Cytokines containing interleukin (IL)-4, IL-17, interferon (IFN)-γ, granzyme B and tumour necrosis factor (TNF)-α released by MAIT and γδT cells were measured following PMA and ionomycin stimulation. Results Circulating MAIT and γδT cells were deficient in OLP. The percentage of CD4 + , CD69 + , CD103 + and PD-1 + MAIT cells was increased in OLP, while that of CD8 + and CD49d + MAIT cells was decreased. The percentage of CD103 + , PD-1 + and PD-L1 + γδT cells was upregulated in OLP. Both the MAIT and γδT cells in OLP produced less IL-4 than controls. The granzyme B-producing MAIT cells were increased, while γδT cells secreting granzyme B and TNF-α were reduced in OLP. IL-17 and IFN-γ in OLP MAIT and γδT cells were not significantly different from that in controls. The frequency of OLP MAIT cells and the MAIT/γδT rate were positively associated with the disease severity. Conclusion The deficient MAIT and γδT cells expressing functional proteins and releasing cytokines may play an immunoregulatory role in the pathogenesis of OLP.
研究领域:
免疫学
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炎症
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口腔疾病
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2024
·
IF 5.7
Lu Chenhe,Li Haimin,Chen Wenjing,Li Hui,Ma Jiayu,Peng Peng,Yan Yan,Dong Weiren,Jin Yulan,Pan Shiyue,Shang Shaobin,Gu Jinyan,Zhou Jiyong
Introduction: Variant pseudorabies virus (PRV) is a newly emerged zoonotic pathogen that can cause human blindness. PRV can take advantage of its large genome and multiple non-essential genes to construct recombinant attenuated vaccines carrying foreign genes. However, a major problem is that the foreign genes in recombinant PRV are only integrated into the genome for independent expression, rather than assembled on the surface of virion.Methods: We reported a recombinant PRV with deleted gE/TK genes and an inserted porcine circovirus virus 2 (PCV2) Cap gene into the extracellular domain of the PRV gE gene using the Cre-loxP recombinant system combined with the CRISPR-Cas9 gene editing system. This recombinant PRV (PRV-Cap), with the envelope-embedded Cap protein, exhibits a similar replication ability to its parental virus.Results: An immunogenicity assay revealed that PRV-Cap immunized mice have 100% resistance to lethal PRV and PCV2 attacks. Neutralization antibody and ELISPOT detections indicated that PRV-Cap can enhance neutralizing antibodies to PRV and produce IFN-γ secreting T cells specific for both PRV and PCV2. Immunological mechanistic investigation revealed that initial immunization with PRV-Cap stimulates significantly early activation and expansion of CD69+ T cells, promoting the activation of CD4 Tfh cell dependent germinal B cells and producing effectively specific effector memory T and B cells. Booster immunization with PRV-Cap recalled the activation of PRV-specific IFN-γ+IL-2+CD4+ T cells and IFN-γ+TNF-α+CD8+ T cells, as well as PCV2-specific IFN-γ+TNF-α+CD8+ T cells.Conclusion: Collectively, our data suggested an immunological mechanism in that the recombinant PRV with envelope-assembled PCV2 Cap protein can serve as an excellent vaccine candidate for combined immunity against PRV and PCV2, and provided a cost-effective method for the production of PRV- PCV2 vaccine.
研究领域:
病毒学
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免疫学
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分子生物学
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疫苗开发
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Cong Cong,Xuejiao Gao,Fei Ye,Xuwu Zhang,Yuchu He,Zhenhe Ma,Wenkang Tu,Weili Xue,Kelong Fan,Dawei Gao
In cancer, the infiltration of immune cells is significantly impeded by aberrantly elevated tumor interstitial fluid pressure (TIFP, a typical mechanical force). For reducing TIFP to augment immunoinfiltration, we synthesized a Fe-doped crystalline carbon nitride as nano-actuators (CFL@M), which can effectively reduce TIFP by piezo/photo-catalytically interstitial fluid splitting. As the mechanical forces change in tumors (TIFP decreased to 60.79%), the trafficking of immune cells into deep tumor tissue were notably facilitated. Among them, the infiltration of dendritic cells was enhanced by 13.02%, and that of M1-type macrophages was enhanced by 30.34%. Moreover, CD4 + T cells and CD8 + T cells responded to changes of fluid pressure by aggregating towards the tumor center. Therefore, the nano-actuators provide a promising mechanosensitive immunotherapy by reducing interstitial fluid pressure to sustain an effective infiltration of immune cells, which results in significant therapeutic benefits such as retarded tumor growth (72.6%), inhibited tumor metastasis (76.56%) and extended survivals. Briefly, this nano-actuator with good biosafety is a new endeavor in the field of “mechano-immunology”.
研究领域:
纳米技术
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免疫治疗
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癌症生物学
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力学生物学
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生物工程
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
·
2021
·
IF 12.479
Qi Sun,Zhenzhen Yang,Meng Lin,Yiwei Peng,Rudong Wang,Yitian Du,Yu Zhou,Jiajia Li,Xianrong Qi
Phototherapy and immunogenic cell death (ICD) are powerful strategies to fight cancer. However, their therapeutic outcomes are diminished by immunosuppressive and hypoxia microenvironment . Herein, a photo-based, immunomodulating and hypoxia-alleviated nanosystem , [email protected] , is proposed to achieve the synergism between phototherapy and immunotherapy. Catalase (CAT) and anti-GITR antibody (DTA-1) are loaded to photothermal agent and photosensitizer composed PDA-ICG nanoparticles . The [email protected] exhibits intrinsic local hyperthermia and enhanced ROS generation in tumor, and abrogates tumor immune suppression. It results in reduction of intratumoral FOXP3 + regulatory T cells (4.3-fold) and increase of CD4 + effector T cells (1.5-fold) compare with the control, and promotes damage associated molecular patterns generation to reinvigorate ICD effect. The potent antitumor of [email protected] is proved in 4T1 bilateral tumor-bearing mice, with inhibition ratio of 95.1% for primary cancers and 68.7% for abscopal cancers. Our findings highlight great promise of the constructed versatility nanosystem to fix bottlenecks for cancer therapy.
研究领域:
肿瘤学
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免疫治疗
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纳米技术
·
癌症生物学
✓ 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）