JOURNAL OF CONTROLLED RELEASE
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2024
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IF 10.5
Xiaoli Ling,Zhipeng Tian,Dong Chen,Yujia Zhang,Ziyan Dong,Dan He,Jiayu Li,Zhidi He,Jiaxin Li,Fang Chen,Qin He,Man Li
Self-adjuvanted vaccine delivery platforms possess potential for targeted delivery of antigens and initiation of potent immune responses. Although aluminum-containing adjuvants have been approved and widely used in human vaccines, their effectiveness in inducing Th1-type immune responses is far from satisfactory. To facilitate antigen delivery and activate potent antitumor immune responses, a self-adjuvanted nanovaccine (CPBG-Al@OVA) is constructed by functionalizing aluminum hydroxide with β-1,3-glucan, which recognizes pattern recognition receptors via Dectin-1. Carboxymethyl-phosphorylated β-1,3-glucan (CPBG) has been synthesized and optimized to achieve superior adjuvanticity while maintaining water solubility. CPBG then self-assembles with aluminum hydroxide and the targeted antigen, leading to the formation of a nanovaccine CPBG-Al@OVA. Owing to the favorable nanoscale size distribution, CPBG-Al@OVA effectively drains to the lymph nodes and is internalized by antigen-presenting cells (APCs) through Dectin-1-mediated endocytosis, activating the Syk and Raf1 signaling pathways and leading to upregulated TNFSF15 and OX40L expression to activate APCs. Following immunization, CPBG-Al@OVA activates potent CD8 + T cell and humoral responses to inhibit tumor growth. Notably, mice vaccinated with CPBG-Al@OVA showed extended survival, with more than 70 % of the mice surviving for over 50 days post-tumor challenge. Moreover, the CPBG-Al nanoparticle also possesses personalized immune-activating capacity by encapsulating tumor lysate as an antigen, specifically suppressing tumor growth. This strategy synergizes the adjuvant effects of aluminum and β-1,3-glucan, offering a platform for self-adjuvanted nanovaccine design with significant clinical translational potential.
研究领域:
免疫学
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癌症研究
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疫苗学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2017
·Vol. 5
·期 48
·9532-9545
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IF 4.543
Meng Lv,Sha Li,Haijie Zhao,Kewei Wang,Qianqian Chen,Zhong Guo,Zonghua Liu,Wei Xue
In order to enhance the cellular immune response of vaccines, numerous vaccine delivery systems have been developed, especially cationic nanoparticle carriers. Cationic polymer dots (PDs) have been widely used for biomedical imaging and drug delivery due to their excellent photoluminescence, small size and abundant positive charge. In this study, polyethyleneimine (600 Da) (PEI600)-modified redox-responsive hyperbranched poly(amido amine) (PAA-PEI600) and partially carbonized PAA-PEI600 PDs were designed and prepared as vaccine carriers to deliver the model antigen protein ovalbumin (OVA). Then, OVA-specific immune responses induced by PAA-PEI600/OVA and PDs/OVA nanoparticles were evaluated in vivo. The results suggest that the PAA-PEI600/OVA and PDs/OVA nanoparticles enhanced OVA-specific immune responses when compared to OVA alone. Further, PDs/OVA nanoparticles induced more potent OVA-specific cellular immune responses, including higher levels of the OVA-specific IgG2a/IgG1 antibody ratio, splenocyte proliferation, IL-12 and IFN-γ cytokines, maturation of dendritic cells, effector memory CD4+ T cells and CD8+ T cells as well as cytotoxic T lymphocytes (CTLs) than PAA-PEI600/OVA nanoparticles did. Moreover, subcutaneously injected PDs/OVA nanoparticles significantly inhibited tumor growth of the mice bearing E.G7-OVA tumor and extended mice survival. All the results show that immunization with PDs/OVA nanoparticles elicited more effective OVA-specific cellular immune responses. PDs could serve as promising vaccine delivery systems for cancer immunotherapy.
研究领域:
生物医学工程
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免疫学
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癌症研究
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药学
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DOI
PubMed
高影响因子
Biomaterials Science
·
2023
·
IF 6.6
Zixu Liu,Linxuan Zhao,Yupeng Feng,Qingqing Wang,Nan Dong,Yu Zhang,Tian Yin,Haibing He,Xing Tang,Jingxin Gou,Li Yang
Cancer vaccine-based immunotherapy has great potential; however, vaccine has been hindered by the immunosuppressive tumor microenvironment (TME). In this study, dual-responsive PEG-lipid polyester nanoparticles (PEG BR647-NP) for tumor-targeted delivery were proposed. PEG BR647-NP containing model tumor associated antigen (TAA) OVA and signal transduction and activator of transcription 3 (STAT3) siRNA were delivered to tumor. PEG BR647-NP was internalized by tumor associated dendritic cells (TADCs), where TAA and siRNA were released into cytoplasm via endo/lysosome escape effect. The released OVA was presented by the major histocompatibility complex class I to activate T cells, the released STAT3 siRNA acted to relieve TADCs dysfunction, promote TADCs maturation, improve antigen-presenting ability, and enhance anticancer T cell immunity. Meanwhile, PEG BR647-NP was ingested by tumor cells, and could kill tumor cells by the pro-apoptosis effect of STAT3 siRNA. Moreover, PEG BR647-NP could reduce the proportion of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in tumors and abrogate immunosuppression. The integration of relieved TADCs dysfunction, promoted TADCs maturation, enhanced antigen cross-presentation, abrogated immunosuppression, and improved pro-apoptosis effect can boost the vaccination for tumor immunotherapy. Thus, PEG BR647-NP efficiently delivered vaccine and STAT3 siRNA to tumor, and modulated immunosuppressive TME, provided better antitumor effects.
研究领域:
癌症免疫疗法
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纳米技术
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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
Fundamental Research
·
2023
·
IF 6.2
Liping Liu,Jiayu Zhao,Zichao Huang,Yudi Xu,Hongyu Chen,Ruirui Qiao,Wantong Song,Zhaohui Tang,Thomas P. Davis,Xuesi Chen
ABSTRACT In recent years, the use of nanotechnologies to improve immunotherapy efficiency has attracted increasing interest in preventive and therapeutic cancer vaccine design. However, current nanocarriers are restricted by difficulties in the systematic spatial coordinative transport of antigens, which greatly hampers the immune response efficacy of nanovaccines. Herein, we designed a mannan-decorated stimulator of the interferon genes (STING)-activating vaccine carrier for spatial coordinative stimulation of antigen-specific immune responses and elicitation of robust antitumor immunity. Mannan-decoration as the shell could significantly enhance the lymph node draining ability of the nanovaccines, especially in CD8 + dendritic cells (DCs). Azole molecule end-capped polylactic acid-polyethylenimine (PLA-PEI-4BImi) with innate stimulating activity was applied as the inner core for coordinating antigen-presenting cell (APC) activation and antigen cross-presentation. In the in vivo therapy study, single usage of this nanovaccine could achieve a 93% tumor suppression rate in the B16-OVA tumor model, which is superior to the commercialized aluminum adjuvant. This study demonstrates that a rational design of vaccine carriers for solving spatial transmission issues could greatly improve cancer vaccine efficiencies.
研究领域:
纳米技术
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免疫学
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癌症研究
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生物医学工程
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药学
✓ 已验证
DOI
PubMed
高影响因子
INFLAMMATION
·
2023
·
IF 5.1
Feng Yong,Hu Jiapeng,Liu Fen,Shang Yunxiao
Asthma is a chronic inflammatory disease characterized by airway remodeling and lung inflammation. Collagen triple helix repeat containing 1 (CTHRC1), a glycoprotein, is involved in multiple pathological processes, including inflammation and fibrosis. However, the function of CTHRC1 in asthma remains unclear. In the present study, the mouse asthma model was successfully generated by sensitizing and challenging mice with ovalbumin (OVA). CTHRC1 expression at both RNA and protein levels was significantly upregulated in lung tissues of asthmatic mice. Asthmatic mice exhibited significant airway remodeling as evidenced by increased bronchial wall and smooth muscle cell layer thickness, goblet cell hyperplasia and collagen deposition, and epithelial-mesenchymal transition (EMT), but those characteristics were reversed by CTHRC1 silencing. The cell model with transforming growth factor-β1 (TGF-β1) induction in bronchial epithelial cells (BEAS-2B) was conducted to verify the effects of CTHRC1 on EMT, a classic mechanism that mediates airway remodeling. The results showed that TGF-β1 stimulation increased CTHRC1 expression, and CTHRC1 knockdown inhibited TGF-β1-induced EMT. OVA-treated mice also showed increased inflammatory cell infiltration and the production of OVA-specific immunoglobulin E (IgE), interleukin (IL)-4, IL-5, and IL-13, which were decreased by CTHRC1 downregulation. The effects of CTHRC1 on OVA-induced airway inflammation were further determined by treating BEAS-2B cells with IL-13, in which CTHRC1 knockdown reduced the IL-13-induced secretion of pro-inflammatory factors, including IL-4 and IL-5. In conclusion, these results indicate that CTHRC1 silencing attenuates asthmatic airway remodeling and inflammation in vivo and in vitro, suggesting that CTHRC1 may be a potential target for asthma treatment. Graphical Abstract
研究领域:
免疫学
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呼吸医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Ming Zhao,Chunting He,Xueyun Zheng,Min Jiang,Zhiqiang Xie,Hongjiao Wei,Shujun Zhang,Ying Lin,Jiaheng Zhang,Xun Sun
Vaccines represent one of the most powerful and cost-effective innovations for controlling a wide range of infectious diseases caused by various viruses and bacteria. Unlike mRNA and DNA-based vaccines, subunit vaccines carry no risk of insertional mutagenesis and can be lyophilized for convenient transportation and long-term storage. However, existing adjuvants are often associated with toxic effect and reactogenicity, necessitating expanding the repertoire of adjuvants with better biocompatibility, for instance, designing self-adjuvating polymeric carriers. We herein report a novel subunit vaccine delivery platform constructed via in situ free radical polymerization of C7A (2-(Hexamethyleneimino) ethyl methacrylate) and acrylamide around the surface of individual protein antigens. Using ovalbumin (OVA) as a model antigen, we observed substantial increases in both diameter (∼70 nm) and surface potential (−1.18 mV) following encapsulation, referred to as n( OVA )C7A. C7A's ultra pH sensitivity with a transition pH around 6.9 allows for rapid protonation in acidic environments. This property facilitates crucial processes such as endosomal escape and major histocompatibility complex (MHC)-I-mediated antigen presentation, culminating in the substantial CD8 + T cell activation. Additionally, compared to OVA nanocapsules without the C7A components and native OVA without modifications, we observed heightened B cell activation within the germinal center, along with remarkable increases in serum antibody and cytokine production. It's important to note that mounting evidence suggests that adjuvant effects, particularly its targeted stimulation of type I interferons (IFNs), can contribute to advantageous adaptive immune responses. Beyond its exceptional potency, the nanovaccine also demonstrated robust formation of immune memory and exhibited a favorable biosafety profile. These findings collectively underscore the promising potential of our nanovaccine in the realm of immunotherapy and vaccine development.
研究领域:
免疫学
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疫苗开发
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纳米技术
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
FOOD HYDROCOLLOIDS
·
2024
·
IF 11
Lechuan Wang,Xiaoyi Cheng,Hanying Lan,Longwei Jiang,Xiuqing Liu,Jianfei Pei,Ming Zhang,Qiuping Zhong,Weijun Chen,Wenxue Chen,Haiming Chen
While both protein-polysaccharide complexes and continuous phase gelation showed great potential for stabilizing high internal phase Pickering emulsions (HIPPEs), it is not known which strategies are more effective and adaptive. In this work, HIPPEs gel was prepared by Ca 2+ -induced continuous phase gelation of ovalbumin (OVA)-low methoxyl pectin (LMP) electrostatic complexes particles (OLECP)-stabilized HIPPEs. The microstructure, rheological properties, stability, and application of HIPPEs and HIPPEs gel were systematically investigated and compared at different LMP concentrations. The results showed that, compared to HIPPEs, continuous phase gelation effectively improved the viscoelasticity, water binding capacity, and hardness of HIPPEs gel due to its robust and developed interface architecture. CLSM and cryo-SEM observations revealed that OLECP interconnected with each other in the continuous phase to form an advanced network architecture in HIPPEs. Whereas, a firm gel network structure and a thick interfacial layer were found in HIPPEs gel. More importantly, with increasing pectin concentration, the cross-linking phenomenon of OLECP mainly at the interface, transformed into the gelation behavior of excess pectin molecules dominating in the continuous phase. LMP contributed to the formation of a finer 3D gel network structure and a firmer interfacial layer, providing a smaller oil droplet size and superior stability for HIPPEs gel. The photochemical stability of curcumin was increased from 16.1 ± 1.5 % to 93.7 ± 2.2 % after encapsulation in HIPPEs gel. In vitro digestion results testified that HIPPEs gel (10:15, w/w) can promote fat hydrolysis (from 32.35 ± 3.06 % to 45.52 ± 2.75 %) and enhance the bioaccessibility of curcumin (from 20.1 ± 1.5 % to 32.8 ± 2.6 %) compared to bulk oil. Besides, compared with HIPPEs, HIPPEs gel showed poor printability because of improper printing adaptability and liquidity. In a nutshell, our work provides valuable information for developing novel HIPPEs gels for various food applications.
研究领域:
食品科学
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材料科学
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化学工程
·
胶体与界面科学
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产品关联
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Zhiting Cao,Jianye Ren,Yuguan Huang,Tong Li,Zhen Wang,Zhangyi Miao,Jia Jia,Yang Ding
Epidermal immunotherapy represents an emerging treatment method for allergic diseases. Nevertheless, an unformidable obstacle for epidermal drug delivery is the dense stratum corneum of the skin. Here, iontophoresis technology is utilized for epidermal delivery of allergen protein. Briefly, an iontophoresis patch consists of conductive nanofiber polypyrrole (PPy) and polyvinyl alcohol (PVA) by electrospinning technology, onto which cationic lipid dioctadecyl–dimethylammonium bromide vesicles containing ovalbumin (DDA@OVA) are loaded via electrospraying technology, forming a stable in situ composite structure. Compared with DDA@OVA/PVA, DDA@OVA/PPy-PVA demonstrated a significant increase in both allergen release and penetration into the epidermis. Ultimately, a high-level activation of antigen-presenting cells is facilitated. Importantly, DDA@OVA/PPy-PVA induces a significant increase in the levels of helper T cell 1 (Th1)-related cytokines such as IFN-γ and IL-12, inhibits the differentiation of T cells into Th2 cells, and further affects the secretion of OVA-specific IgE and promotes the production of protective antibody IgG. The lung tissue analysis illustrates that DDA@OVA/PPy-PVA treatment achieves regular alveolar structures in the lumen and significantly relieved asthma symptoms. The findings indicate that iontophoresis patches provide multiple benefits, including drug-responsive release, efficient penetration, and advanced therapeutic efficacy. These attributes make iontophoresis patches a promising treatment option for allergic diseases.
研究领域:
生物医学工程
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药学
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免疫学
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过敏研究
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药物递送系统
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纳米技术
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材料科学
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呼吸系统疾病
✓ 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）