Nanocarriers for effective delivery: modulation of innate immunity for the management of infections and the associated complications

Ko, Chung-Nga; Zang, Shaohong; Zhou, Yingtang; Zhong, Zhangfeng; Yang, Chao

doi:10.1186/s12951-022-01582-8

Cited by 15 publications

(11 citation statements)

References 268 publications

(277 reference statements)

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“…Additionally, activated APCs usually express high levels of costimulatory molecules CD80 and CD86, which play a crucial role in presenting antigens and activating naive T cells by providing essential signals. 60 As shown in Figure 3D−G, the Pam 3 CSK 4 −BSA-MUC1 conjugate evoked a higher ratio of 17 To assess the capacity of the vaccine candidates to activate innate immune responses in vivo, the secretion of IL-6 and IL-12 in mouse sera was measured using an ELISA assay. As shown in Figure 6A,B, the Pam 3 CSK 4 −BSA-MUC1 vaccine candidate induced significantly higher levels of cytokine secretion (5354 pg/mL for IL-6 and 2578 pg/mL for IL-12) compared to the BSA-MUC1 + Pam 3 CSK 4 group, which exhibited levels approximately five times lower (891 pg/mL for IL-6 and 508 pg/mL for IL-12).…”

Section: Journal Of Medicinal Chemistrymentioning

confidence: 99%

“…Additionally, adjuvants also play a crucial role in vaccines for enhancing the immunogenicity of antigens and boosting immune responses. − In vaccine designs, adjuvants are typically physically mixed with antigens and bolster antigen-specific immune responses by activating innate immunity, such as aluminum-containing adjuvants (Alum adjuvant), invariant natural killer T (iNKT) cell agonists, toll-like receptors (TLR) agonists, − and stimulator of interferon genes (STING) agonists. , However, the direct administration of adjuvants may result in the dispersion of adjuvants from the injection site, which may reduce the effective concentration of adjuvants and trigger inflammation or systemic toxicity . In recent years, the adjuvant-antigen conjugation strategy has been demonstrated to be an effective vaccine design approach. − Built-in adjuvant molecules may confer various advantages to vaccines, including reproducibility, controllability, and uniform chemical composition .…”

Section: Introductionmentioning

confidence: 99%

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Multifunctional Lipidated Protein Carrier with a Built-In Adjuvant as a Universal Vaccine Platform Potently Elevates Immunogenicity of Weak Antigens

Zhou,

Zhang,

Wen

et al. 2024

J. Med. Chem.

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Weak antigens represented by MUC1 are poorly immunogenic, which greatly constrains the development of relevant vaccines. Herein, we developed a multifunctional lipidated protein as a carrier, in which the TLR1/2 agonist Pam 3 CSK 4 was conjugated to the N-terminus of MUC1-loaded carrier protein BSA through pyridoxal 5′phosphate-mediated transamination reaction. The resulting Pam 3 CSK 4 − BSA-MUC1 conjugate was subsequently incorporated into liposomes, which biomimics the membrane structure of tumor cells. The results indicated that this lipidated protein carrier significantly enhanced antigen uptake by APCs and obviously augmented the retention of the vaccine at the injection site. Compared with the BSA-MUC1 and BSA-MUC1 + Pam 3 CSK 4 groups, Pam 3 CSK 4 −BSA-MUC1 evoked 22-and 11-fold increases in MUC1-specific IgG titers. Importantly, Pam 3 CSK 4 −BSA-MUC1 elicited robust cellular immunity and significantly inhibited tumor growth. This is the first time that lipidated protein was constructed to enhance antigen immunogenicity, and this universal carrier platform exhibits promise for utilization in various vaccines, holding the potential for further clinical application.

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Section: Journal Of Medicinal Chemistrymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Multifunctional Lipidated Protein Carrier with a Built-In Adjuvant as a Universal Vaccine Platform Potently Elevates Immunogenicity of Weak Antigens

Zhou,

Zhang,

Wen

et al. 2024

J. Med. Chem.

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“…Understanding the function and regulatory mechanisms of metalloproteinases may provide insights into the future development of diagnostic and therapeutic approaches (e.g. nanomaterials or metal-based probe targeting these enzymes) for chronic inflammatory diseases ( 20 – 24 ).…”

Section: Othersmentioning

confidence: 99%

Editorial: Immunomodulatory role of metalloproteases in chronic inflammatory diseases

Yang

et al. 2023

Front. Immunol.

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Editorial on the Research TopicImmunomodulatory role of metalloproteases in chronic inflammatory diseases Metalloproteases are a diverse class of enzymes involved in the regulation of numerous pathological and physiological processes. Evidence has shown that metalloproteases could either directly or indirectly regulate the secretion of chemokines and the differentiation and/or activation of immune cells, thereby mediating many inflammatory and innate immune responses (1, 2). While different metalloproteases could have substantially different primary structure, their active center which contains metal ions (e.g. iron, zinc, cobalt, nickel ions) is relatively conservative. Metalloprotease relies on metal ions to maintain its catalytic function. Studies have shown that metal chelators such as EDTA could completely inactivate metalloproteases (3-6; Liu et al.). Under inflammatory conditions, metalloproteases are constitutively activated or deactivated in multiple immune-or non-immune cells and could contribute to a variety of inflammatory diseases, such as rheumatoid arthritis (RA) (Li et al.), chronic enteritis (Deng et al. and Mei et al.), allergic dieseases (Wang and Wang and Bendavid et al.), diabetes (Chen et al.), and cancers (He et al.), etc. Mutiple chronic inflammatory diseases could even hijack various metalloproteases to promote and exacerbate inflammation (1, 2). Numerous preclinical and clinical studies have shown that metalloprotease modulators, including lysine-specific demethyalses (KDMs) inhibitors (3-5, 7), histone deacetylases (HDACs) inhibitors (8), and matrix metalloproteinases (MMPs) inhibitors (6), and a disintegrin and metalloproteinases (ADAMs) inhibitors (9), possess in vitro and in vivo anti-inflammatory activities. Therefore, understanding the roles of metalloproteinases in the immune system may potenitally uncover new targets for the diagnosis and treatment of chronic inflammatory diseases.

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“…Targeted immunomodulators may be useful in the treatment of such diseases and their complications. However, the disadvantages of immunomodulators include high immune-mediated toxicity, low solubility, and) loss of biological activity after long-term circulation ( Ko et al, 2022 ). At this stage, nanocarriers have become a very promising tool to overcome these barriers due to their unique properties such as continuous circulation, ideal biodistribution, and preferred pharmacokinetic and pharmacodynamic properties.…”

Section: Immunotherapymentioning

confidence: 99%

Activation of cancer immunotherapy by nanomedicine

Wang

Xu²,

Weng³

et al. 2022

Front. Pharmacol.

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Cancer is one of the most difficult diseases to be treated in the world. Immunotherapy has made great strides in cancer treatment in recent years, and several tumor immunotherapy drugs have been approved by the U.S. Food and Drug Administration. Currently, immunotherapy faces many challenges, such as lacking specificity, cytotoxicity, drug resistance, etc. Nanoparticles have the characteristics of small particle size and stable surface function, playing a miraculous effect in anti-tumor treatment. Nanocarriers such as polymeric micelles, liposomes, nanoemulsions, dendrimers, and inorganic nanoparticles have been widely used to overcome deficits in cancer treatments including toxicity, insufficient specificity, and low bioavailability. Although nanomedicine research is extensive, only a few nanomedicines are approved to be used. Either Bottlenecks or solutions of nanomedicine in immunotherapy need to be further explored to cope with challenges. In this review, a brief overview of several types of cancer immunotherapy approaches and their advantages and disadvantages will be provided. Then, the types of nanomedicines, drug delivery strategies, and the progress of applications are introduced. Finally, the application and prospect of nanomedicines in immunotherapy and Chimeric antigen receptor T-cell therapy (CAR-T) are highlighted and summarized to address the problems of immunotherapy the overall goal of this article is to provide insights into the potential use of nanomedicines and to improve the efficacy and safety of immunotherapy.

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Nanocarriers for effective delivery: modulation of innate immunity for the management of infections and the associated complications

Cited by 15 publications

References 268 publications

Multifunctional Lipidated Protein Carrier with a Built-In Adjuvant as a Universal Vaccine Platform Potently Elevates Immunogenicity of Weak Antigens

Multifunctional Lipidated Protein Carrier with a Built-In Adjuvant as a Universal Vaccine Platform Potently Elevates Immunogenicity of Weak Antigens

Editorial: Immunomodulatory role of metalloproteases in chronic inflammatory diseases

Activation of cancer immunotherapy by nanomedicine

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