Polyethyleneimine-based immunoadjuvants for designing cancer vaccines

Yang, Xi; Wei, Yuanfeng; Liu, Zheng; You, Jia; Li, Huawei; Gao, Ling; Gong, Changyang; Yi, Cheng

doi:10.1039/d2tb01358d

Cited by 8 publications

(4 citation statements)

References 108 publications

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“…Therefore, fluorinated NPs hold great potential to enhance cytosolic delivery. One group constructed a personalized nanovaccine (F-PEI/OVA NPs) prepared by mixing the fluoroalkane-grafted polyethyleneimines (F-PEIs) with a model antigen ovalbumin (OVA) [206]. When incubating F-PEI/OVA NPs with mouse bone marrow-derived dendritic cells (BMDCs), F-PEI/OVA NPs showed a significantly higher cellular uptake and endosomal escape compared with PEI/OVA NPs and bare OVA.…”

Section: Fluorinated Npsmentioning

confidence: 99%

Recent advances in nano/micro systems for improved circulation stability, enhanced tumor targeting, penetration, and intracellular drug delivery: a review

Chan,

2024

Biomed. Phys. Eng. Express

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In recent years, nanoparticles (NPs) have been extensively developed as drug carriers to overcome the limitations of cancer therapeutics. However, there are several challenges to nanomedicines, which include the lack of stability in circulation, limited target specificity, low penetration into tumors and insufficient cellular uptake, restricting the active targeting toward tumors of nanomedicines. To address these challenges, a variety of promising strategies were developed recently, as they can be designed to improve NP accumulation and penetration in tumor tissues, circulation stability, tumor targeting, and intracellular uptake. In this Review, we summarized nanomaterials developed in recent three years that could be utilized to improve drug delivery for cancer treatments.

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Section: Fluorinated Npsmentioning

confidence: 99%

Recent advances in nano/micro systems for improved circulation stability, enhanced tumor targeting, penetration, and intracellular drug delivery: a review

Chan,

2024

Biomed. Phys. Eng. Express

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“…6 However, the design of these compounds often presents challenges including biological toxicity, biodegradability, and non-specificity for DCs. 7 Hence, current research is directed towards pH-responsive, photo-sensitive, or thermo-sensitive biomaterials for achieving lysosomal escape. [8][9][10][11][12] Apart from achieving proficient antigen delivery, the immunogenicity and adjuvant potential of nanovaccine are of paramount importance.…”

Section: Introductionmentioning

confidence: 99%

Enhancing Dendritic Cell Activation Through Manganese-Coated Nanovaccine Targeting the cGAS-STING Pathway

Wang,

Gao,

et al. 2024

IJN

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Background Nanovaccines have emerged as a promising vaccination strategy, exhibiting their capacity to deliver antigens and adjuvants to elicit specific immune responses. Despite this potential, optimizing the design and delivery of nanovaccines remains a challenge. Methods In this study, we engineered a dendritic mesoporous silica-based nanocarrier enveloped in a metal-phenolic network (MPN) layer containing divalent manganese ions and tannic acid (MSN@MT). This nanocarrier was tailored for antigen loading to serve as a nanovaccine, aiming to activate the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway in dendritic cells (DCs). Our experimental approach encompassed both cellular assays and mouse immunizations, allowing a comprehensive evaluation of the nanovaccine’s impact on DC activation and its influence on the generation of antigen-specific T-cell responses. Results MSN@MT demonstrated a remarkable enhancement in humoral and cellular immune responses in mice compared to control groups. This highlights the potential of MSN@MT to effectively trigger the cGAS-STING pathway in DCs, resulting in robust immune responses. Conclusion Our study introduces MSN@MT, a unique nanocarrier incorporating divalent manganese ions and tannic acid, showcasing its exceptional ability to amplify immune responses by activating the cGAS-STING pathway in DCs. This innovation signifies a stride in refining nanovaccine design for potent immune activation.

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“…Besides, PEI itself appears to be intrinsically immunostimulatory, for example, capable of activating antigen-presenting cells (APCs) through Toll-like receptor 4 (TLR-4) signaling, 37−39 inducing reactive oxygen species (ROS) generation, 40 nucleotide-binding oligomerization domain-like receptors (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome pathways, and danger signaling pathways. 41 PEI may also facilitate the cross-presentation of antigens through the "proton sponge" effect. 42,43 It is wellknown that PEI can induce cell apoptosis and necrosis.…”

Section: ■ Introductionmentioning

confidence: 99%

“…It is widely studied as a delivery polymer and appears to play multiple functional roles in cancer immunotherapy for its ability to combine a variety of anionic immunotherapeutic agents, such as protein antigen (ovalbumin, OVA), immune adjuvant (CpG oligodeoxynucleotide), and hairpin RNA (shMFN1) or microRNA (miR-125a) − for modulating the immune-related cells or pathways. Besides, PEI itself appears to be intrinsically immunostimulatory, for example, capable of activating antigen-presenting cells (APCs) through Toll-like receptor 4 (TLR-4) signaling, − inducing reactive oxygen species (ROS) generation, nucleotide-binding oligomerization domain-like receptors (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome pathways, and danger signaling pathways . PEI may also facilitate the cross-presentation of antigens through the “proton sponge” effect. , It is well-known that PEI can induce cell apoptosis and necrosis .…”

Section: Introductionmentioning

confidence: 99%

PEI-Based Nanoparticles for Tumor Immunotherapy via In Situ Antigen-Capture Triggered by Photothermal Therapy

Chen,

Zhang,

Wang

et al. 2023

ACS Appl. Mater. Interfaces

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Activating a tumor antigen-specific immune response is key to the success of tumor immunotherapy and the development of personalized antitumor therapy. Nanocarriers can capture, enrich, and protect in situ produced tumor antigens due to immunogenic cell death (ICD), thus enhancing the tumor-specific immune response. Developing multifunctional nanocarriers that combine multiple antigen capturing mechanisms is crucial to the activation of tumor-specific immune responses. In this study, polyethylenimine (PEI) was employed as a main building block to construct a series of multifunctional indocyanine green (ICG)-loaded nanoparticles to capture antigens via multiple mechanisms: electrostatic interactions with PEI, hydrophobic interactions with the thermosensitive segment (POEGMA300), and covalent bonding with the pyridyl disulfide (PDS) groups, respectively. Their capacity of ICD induction, tumor antigen-capture, and antitumor immune responses were evaluated. Both the intrinsic toxicity of PEI and the ICG-mediated photothermal effect were responsible for inducing ICD. The positively charged PEI segment exhibited the best antigen-capturing ability via electrostatic interactions, promoted bone marrow-derived dendritic cell maturation and CD8+ T cell proliferation, and elicited antitumor immune responses in vivo. PDS groups bonded antigens covalently and significantly contributed to the suppression of distant tumor growth. Although the thermosensitive hydrophobic polymer segment did not contribute positively to antigen capture or tumor growth inhibition, NPs containing all of the functional modules prolonged the survival of tumor-bearing mice more than other treatments. This study provides more chemical insights into the design of polymer-based in situ nanovaccines against cancer.

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Polyethyleneimine-based immunoadjuvants for designing cancer vaccines

Abstract: PEI-based cancer vaccines increase the cellular uptake of antigens and adjuvants by dendritic cells and promote activation and antigen cross-presentation to effectively cross-prime antigen-specific T cells and B cells for robust antitumor immunity.

Cited by 8 publications

References 108 publications

Recent advances in nano/micro systems for improved circulation stability, enhanced tumor targeting, penetration, and intracellular drug delivery: a review

Recent advances in nano/micro systems for improved circulation stability, enhanced tumor targeting, penetration, and intracellular drug delivery: a review

Enhancing Dendritic Cell Activation Through Manganese-Coated Nanovaccine Targeting the cGAS-STING Pathway

PEI-Based Nanoparticles for Tumor Immunotherapy via In Situ Antigen-Capture Triggered by Photothermal Therapy

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