JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2025
·
IF 4.9
Changmei Chen,Qinghua Yu,Lulu Wang,Rongchun Yi,Siying Huang,Xiangshu Cheng,Tao Deng
Chemotherapy combined with immunotherapy represents a promising combination therapy for tumor treatment. The low targeting of chemotherapeutic drugs and the potential immune-related adverse events (irAEs) of immune adjuvants hinder the realization of combination therapy. To solve these problems, we propose to further conjugate immunoadjuvant OVA using boric acid (BA) modified drug-carrying carbon dots, and develop a multifunctional nano drug delivery system for hierarchical targeting of focal sites (RCD@DOX/BA-O). From a mechanistic perspective, based on the pKa of BA, RCD@DOX/BA can couple OVA (1, 3-n-diol) under alkaline conditions and release OVA under tumor microenvironment, which could prevent the occurrence of irAEs. Furthermore, the exposed BA was able to combine with sialic acid (SA) (1, 2-n-diol) under the acidic tumor microenvironment, thereby enhancing its tumor-targeting capabilities. Specially, the immune effect (tumor-associated macrophages (TAMs) to M1) of OVA and the tumor targeted enhancement was verified by cell experiments. The treatment effect of RCD@DOX/BA-O was further proved on animal level. Overall, our finding suggests that the synthesized RCD@DOX/BA-O enabling synergistic chemotherapy and immunotherapy through hierarchical targeting to enhance anti-tumor efficacy and reduce irAEs. It is of great significance for targeted immunotherapy and improving the therapeutic effect of tumor.
研究领域:
纳米医学
·
肿瘤学
·
免疫学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Science
·
2020
·Vol. 7
·期 18
·2000771
·
IF 15.84
Tao Qin,Shang Ma,Xinyu Miao,Yan Tang,Dandan Huangfu,Jinyuan Wang,Jing Jiang,Nuo Xu,Yuncong Yin,Sujuan Chen,Xiufan Liu,Yinyan Yin,Daxin Peng,Lizeng Gao
Influenza poses a severe threat to global health. Despite the whole inactivated virus (WIV)-based nasal vaccine being a promising strategy for influenza protection, the mucosal barrier is still a bottleneck of the nasal vaccine. Here, a catalytic mucosal adjuvant strategy for an influenza WIV nasal vaccine based on chitosan (CS) functionalized iron oxide nanozyme (IONzyme) is developed. The results reveal that CS-IONzyme increases antigen adhesion to nasal mucosa by 30-fold compared to H1N1 WIV alone. Next, CS-IONzyme facilitates H1N1 WIV to enhance CCL20-driven submucosal dendritic cell (DC) recruitment and transepithelial dendrite(TED) formation for viral uptake via the toll-like receptor(TLR) 2/4-dependent pathway. Moreover, IONzyme with enhanced peroxidase (POD)-like activity by CS modification catalyzes a reactive oxygen species (ROS)-dependent DC maturation, which further enhances the migration of H1N1 WIV-loaded DCs into the draining lymph nodes for antigen presentation. Finally, CS-IONzyme-based nasal vaccine triggers an 8.9-fold increase of IgA-mucosal adaptive immunity in mice, which provides a 100% protection against influenza, while only a 30% protection by H1N1 WIV alone. This work provides an antiviral alternative for designing nasal vaccines based on IONzyme to combat influenza infection.
研究领域:
免疫学
·
病毒学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2023
·
IF 14
Bo Chen,Ruijie Huang,Wei Zeng,Wei Wang,Yuanzeng Min
The immunosuppressive tumor microenvironment (TME) greatly limits the actual outcome of immunotherapy. Therefore, it is urgent to develop appropriate strategies to reshape the TME and ultimately induce a strong immune response. Here, we developed a dual-functional liposome loaded with the photothermal agent IR808 near the infrared region (NIR) and Toll-like-receptor-7 (TLR7) agonist loxoribine prodrug (Lipo@IR808@Loxo) to achieve NIR light-triggered photothermal therapy (PTT) and the targeted delivery of immune adjuvants. Under NIR irradiation, Lipo@IR808@Loxo could greatly improve the efficiency of PTT to directly kill tumor cells and release tumor-associated antigens, which could work together with loaded loxoribine to relieve the immunosuppressive TME, effectively promoting the activation of antigen-presenting cells and subsequent antigen presentation . In this way, Lipo@IR808@Loxo could act as an in situ therapeutic cancer vaccine, eventually inducing a potent antitumor T-cell response. When further combined with immune checkpoint blockade, Lipo@IR808@Loxo-mediated photothermal immunotherapy could not only eliminate the primary tumors but also inhibit the growth of distant tumors, thus enhancing the abscopal effect.
研究领域:
肿瘤学
·
免疫学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2012
·
IF 3.35
Tianyi Wang,Haitao Jiang,Qinfu Zhao,Siling Wang,Meijuan Zou,Gang Cheng
Three different kinds of silica (S2, S1 and SBA-15) with different particle sizes (130, 430 nm and 1–2 μm) and different pore characteristics (i.e. pore size and shape) were developed as oral vaccine immunological adjuvants and the relationship between the silica architecture and immunological properties was investigated. The silica particles were characterized using SEM, TEM and nitrogen adsorption. Model antigen bovine serum albumin (BSA) was successfully entrapped into the silica pores to produce a sustained release vaccine delivery system. Compared with the responsiveness induced by parenteral administration of BSA emulsified in Freund's complete adjuvant (FCA), oral immunization with the silica/BSA formulation produced a stimulated humoral and mucosal (sIgA) response. The IgG and IgA titers induced by loading BSA was as follows: S1 > S2 > SBA-15. The highest IgG and IgA titers of S1 were attributed to its large honeycombed pores and the optimal particle diameter of 430 nm. The corresponding IgG1 and IgG2a titers were also investigated to confirm that BSA loaded in nanoparticles by oral immunization can induce both T-helper 1- and T-helper 2- (Th1 or Th2) mediated responses. We believe that the results of our research will open up new avenues for the formulation of oral vaccines.
研究领域:
免疫学
·
纳米医学
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疫苗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Shaozhen Wang,Chen Yang,Yuanyuan Zhang,Yi Hu,Lan Xiao,Weiping Ding,Bensheng Qiu,Fenfen Li
Cancer immunotherapy encounters challenges of a low treatment response rate due to the tumor immunosuppressive microenvironment and immune-related adverse events caused by off-target immunotherapy agents delivered through systemic administration in clinical practice. Photodynamic therapy (PDT) offers a viable approach to improve the immunotherapy efficacy through inducing immunogenic tumor cell death and is particularly advantageous in superficial tumor treatment. Therefore, leveraging integrated nanomaterials for photo-immunotherapy appears to be an ideal strategy to improve therapeutic outcome. In this study, we develop a transdermal-enhancing peptide (TD)-modified cationic liposome that simultaneously encapsulated with photosensitizer chlorine 6 (Ce6) and immunoadjuvant CpG, denoted as Ce6/CpG@Lip-TD, to mediate photo-immunotherapy of superficial tumors via the skin. The functionalization of TD peptide and positively charged surface endow the liposomes enhanced skin penetration capability. The combination of Ce6 and CpG within the liposomes synergistically potentiates the photo-immunotherapy effect when exposed to laser irradiation. In both melanoma and breast cancer murine models, Ce6/CpG@Lip-TD demonstrated substantial tumor-suppressing properties, along with an augmented systemic immune response against distal tumors. As a topical therapeutic agent, Ce6/CpG@Lip-TD circumvents the regulatory challenges associated with the systemic delivery of nanomaterials and significantly reduces systemic side effects, holding great promise for rapid translation into clinical applications.
研究领域:
肿瘤学
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纳米医学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
·
2024
·
IF 6.1
Wen Guo,Xinyue Zhang,Long Wan,Zhiqi Wang,Meiqi Han,Ziwei Yan,Jia Li,Ruizhu Deng,Shenglong Li,Yuling Mao,Siling Wang
Particle size and surface properties are crucial for lymphatic drainage (LN), dendritic cell (DC) uptake, DC maturation, and antigen cross-presentation induced by nanovaccine injection, which lead to an effective cell-mediated immune response. However, the manner in which the particle size and surface properties of vaccine carriers such as mesoporous silica nanoparticles (MSNs) affect this immune response is unknown. We prepared 50, 100, and 200 nm of MSNs that adsorbed ovalbumin antigen (OVA) while modifying β -glucan to enhance immunogenicity. The results revealed that these MSNs with different particle sizes were just as efficient in vitro , and MSNs with β -glucan modification demonstrated higher efficacy. However, the in vivo results indicated that MSNs with smaller particle sizes have stronger lymphatic targeting efficiency and a greater ability to promote the maturation of DCs. The results also indicate that β -glucan-modified MSN, with a particle size of ∼100 nm, has a great potential as a vaccine delivery vehicle and immune adjuvant and offers a novel approach for the delivery of multiple therapeutic agents that target other lymph-mediated diseases.
研究领域:
免疫学
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纳米医学
·
疫苗研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2017
·
IF 2.31
Jianye Wei,Wei Xue,Xifei Yu,Xiaozhong Qiu,Zonghua Liu
In the field of immunotherapy, immune vaccinations have received more and more attention for disease prevention and treatment. In immune vaccination, efficient vaccine adjuvants are necessary due to the weak immunogenicity of vaccines. Some traditional vaccine adjuvants have been widely used but have shown obvious limitations such as poor biosafety. Therefore, researchers make a great effort to develop more functional novel immune adjuvants such as chitosan-based immune adjuvants. However, chitosan is poorly water soluble, which greatly limits its application as immune adjuvants, regardless of its good biocompatibility, biodegradability, and other biological activities. In this work, we prepared a water-soluble chitosan derivative phosphorylated chitosan (PCS) and evaluated its potential as a novel immune adjuvant. PCS was found to be pH sensitive: specifically, it was water soluble at pH < 7.0 but began to gel at pH >7.0. By virtue of this, neutral PCS aqueous solutions containing ovalbumin (OVA) antigen was intramuscularly injected into test mice, which would transform to an OVA-containing gel network for OVA immunization. The results showed that the use of 30 mg/mL PCS-based hydrogel as vaccine delivery system contributed to significantly higher level of antigen-specific immune responses, including higher level of antigen-specific IgG antibodies, IFN-γ and IL-4 cytokines secretion by splenocytes, as well as memory CD4+ and CD8+ T cells. In vivo imaging and immunohistochemistry assays suggest that the improved immunization efficacy may be attributed to the controlled release of antigen from injection site by PCS gel network, and then prolonged antigen stimuli to the immune system. From the results, PCS could be developed as a promising vaccine delivery system for immunotherapy.
研究领域:
免疫学
·
生物材料学
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疫苗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small Science
·
2025
·
IF 8.3
Yanan Li,Jie Teng,Qiuting Chen,Qingze Fan,Hiroyuki Oku,Guanghui Ma,Jie Wu
Adjuvants based on spherical particles and stabilized Pickering emulsions represent a significant area of research in the adjuvant field. However, the immune effects of adjuvants containing nonspherical particles and their stabilized Pickering emulsions remain largely unexplored. Particle shape plays a critical role in influencing particle–cell interactions and antigen storage efficiency. In this study, it is aimed to synthesize nonspherical particles with diverse morphologies and sizes and successfully utilize one type to stabilize Pickering emulsions. In this research, their immunological effects are further evaluated by examining the activation of antigen-presenting cells (APCs) and their impact on both cellular and humoral immunity. In these findings, it is demonstrated that nonspherical particles extend the in vivo residence time of vaccines and enhance APCs activation, thereby improving cellular immunity. Additionally, Pickering emulsions stabilized by nonspherical particles exhibit superior flexibility, higher antigen uptake by APCs, and more robust APCs activation compared to those stabilized by spherical particles. These advantages ultimately result in enhanced humoral and cellular immune responses.
研究领域:
免疫学
·
药剂学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
·
IF 5.2
Chenyao Qian,Huan Wang,Jinyue Bi,Xiaodan Zheng,Rujia Li,Huan Luo,Xueyong Qi,Song Shen,Jin Cao
Cutaneous melanoma is characterized by malignant proliferation, high aggressiveness, high metastasis, rapid recurrence, and low survival rate; therefore, research on its treatment is vital. In this study, a novel nano system combining sonodynamics and immunotherapy for cutaneous melanoma treatment was designed and developed. Based on the use of phycocyanin for the biomineralization of manganese ions, smart and multifunctional manganese phycocyanin nanoparticles encapsulating the immune adjuvant levamisole (LMS) with melanoma B16-OVA cell membranes wrapped around its outer layer (Mn-PCNP-LMS@CM) were designed and prepared. The experimental results showed that Mn-PCNP-LMS@CM efficiently targeted cutaneous melanomas. Under ultrasonic excitation, it catalyzed oxygen production from hydrogen peroxide in the tumor environment, reduced high glutathione levels in tumor tissues, and significantly enhanced (reactive oxygen species) ROS generation, thus improving the outcome of sonodynamic therapy. In contrast, sonodynamic therapy induced immunogenic death of tumor cells, together with the loaded immune adjuvant levamisole, which promoted the maturation of dendritic cells (DCs), modulated the immunosuppressive microenvironment, enhanced the immunotherapeutic effect, and stimulated the function of long-term immune memory to prevent tumor growth and recurrence. This study is expected to provide new ideas for developing novel anti-tumor nano systems and achieving anti-tumor synergistic therapy.
研究领域:
肿瘤学
·
纳米医学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 12
·2733-2744
·
IF 7
Zhang Jing,Lu Jie,Qian Sunxiang,Ni Haifeng,Feng Jie
Chemoimmunotherapy is an effective method to treat cancer, and thus various vehicles have been constructed to co-deliver immune agents and anticancer drugs. But the immune induction process in vivo is highly susceptible to the influence of the material itself. To avoid immune reactions by the materials of delivery systems, herein, a new kind of zwitterionic cryogels (SH cryogels) with extremely low immunogenicity was prepared for chemoimmunotherapy of cancer. Their macroporous structure enabled the SH cryogels to have good compressibility and be injected through a conventional syringe. The loaded chemotherapeutic drugs and immune adjuvants were accurately, locally and long-termly released in the vicinity of tumors, enhancing the outcome of tumor therapy and minimizing the damage caused by the chemotherapeutic drugs to other organ tissues. In vivo tumor treatment experiments indicated that chemoimmunotherapy using the SH cryogel platform could inhibit the growth of breast cancer tumors to the greatest extent. Furthermore, macropores of SH cryogels supported cells to move freely in the cryogels, which could promote the dendritic cells to capture the in situ produced tumor antigens and present them to T cells. The ability to act as cradles for cell infiltration made the SH cryogels promising for applications as vaccine platforms.
研究领域:
生物医学工程
·
肿瘤学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MACROMOLECULAR RAPID COMMUNICATIONS
·
2024
·
IF 4.2
Huan Zhang,Meng Song,Shiya Zhuang,Zining Wang,Hui Shi,Zhuolang Song,Chuanhe Song,Lian Cen
With the continuous development of preventive and therapeutic vaccines, traditional adjuvants cannot provide sufficient immune efficacy and it is of high necessity to develop safe and effective novel nanoparticle-based vaccine adjuvants. α -Tocopherol (TOC) is commonly used in oil-emulsion adjuvant systems as an immune enhancer, yet its bioavailability is limited by poor water solubility. This study aims to develop TOC-loaded poly(lactic- co -glycolic acid) (PLGA) nanoparticles (TOC-PLGA NPs) to explore the potential of TOC-PLGA NPs as a novel nanoparticle-immune adjuvant. TOC-PLGA NPs are prepared by a nanoprecipitation method and their physicochemical properties are characterized. It is shown that TOC-PLGA NPs are 110.8 nm, polydispersity index value of 0.042, and Zeta potential of −13.26 mV. The encapsulation efficiency and drug loading of NPs are 82.57% and 11.80%, respectively, and the cumulative release after 35 days of in vitro testing reaches 47%. Furthermore, TOC-PLGA NPs demonstrate a superior promotion effect on RAW 264.7 cell proliferation compared to PLGA NPs, being well phagocytosed and also promoting antigen uptake by macrophages. TOC-PLGA NPs can strongly upregulate the expression of co-stimulatory surface molecules and the secretion of cytokines. In conclusion, TOC-PLGA NPs can be a novel vaccine adjuvant with excellent biocompatibility and significant immune-enhancing activity.
研究领域:
药剂学
·
免疫学
·
纳米技术
·
疫苗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2021
·Vol. 12
·期 1
·1-16
·
IF 14.919
Wang Yongchao,Gong Ningqiang,Ma Chi,Zhang Yuxuan,Tan Hong,Qing Guangchao,Zhang Jimei,Wang Yufei,Wang Jinjin,Chen Shizhu,Li Xianlei,Ni Qiankun,Yuan Yuan,Gan Yaling,Chen Junge,Li Fangzhou,Zhang Jinchao,Ou Caiwen,Zhao Yongxiang,Liu Xiaoxuan,Liang Xing-Jie
Immunological adjuvants are essential for successful cancer vaccination. However, traditional adjuvants have some limitations, such as lack of controllability and induction of systemic toxicity, which restrict their broad application. Here, we present a light-activable immunological adjuvant (LIA), which is composed of a hypoxia-responsive amphiphilic dendrimer nanoparticle loaded with chlorin e6. Under irradiation with near-infrared light, the LIA not only induces tumour cell lysis and tumour antigen release, but also promotes the structural transformation of 2-nitroimidazole containing dendrimer to 2-aminoimidazole containing dendrimer which can activate dendritic cells via the Toll-like receptor 7-mediated signaling pathway. The LIA efficiently inhibits both primary and abscopal tumour growth and induces strong antigen-specific immune memory effect to prevent tumour metastasis and recurrence in vivo. Furthermore, LIA localizes the immunological adjuvant effect at the tumour site. We demonstrate this light-activable immunological adjuvant offers a safe and potent platform for in situ cancer vaccination.
研究领域:
癌症研究
·
免疫学
·
纳米技术
·
药学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）