An Injectable Hydrogel Reshaping Adenosinergic Axis for Cancer Therapy

Zhao, Zhipeng; Li, Qian; Qin, Xiaohan; Zhang, Mengzhu; Du, Qian; Luan, Yuxia

doi:10.1002/adfm.202200801

Cited by 31 publications

(14 citation statements)

References 29 publications

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“…Inhibition of adenosine generation and signaling pathways have been shown to effectively block the denosine-A2AR pathway ( 131 ). Recently, Zhao et al ( 132 ) introduced adenosine deaminase (ADA) into hydrogels, which enabled the catalytic transformation of adenosine (immunosuppressor) into inosine (an immunopotentiator), thus reversing tumor immunosuppression and enhancing antitumor immune responses.…”

Section: Strategies For Hydrogel-based Cancer Vaccine To Initiate An ...mentioning

confidence: 99%

Hydrogel-guided strategies to stimulate an effective immune response for vaccine-based cancer immunotherapy

et al. 2022

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Cancer vaccines have attracted widespread interest in tumor therapy because of the potential to induce an effective antitumor immune response. However, many challenges including weak immunogenicity, off-target effects, and immunosuppressive microenvironments have prevented their broad clinical translation. To overcome these difficulties, effective delivery systems have been designed for cancer vaccines. As carriers in cancer vaccine delivery systems, hydrogels have gained substantial attention because they can encapsulate a variety of antigens/immunomodulators and protect them from degradation. This enables hydrogels to simultaneously reverse immunosuppression and stimulate the immune response. Meanwhile, the controlled release properties of hydrogels allow for precise temporal and spatial release of loads in situ to further enhance the immune response of cancer vaccines. Therefore, this review summarizes the classification of cancer vaccines, highlights the strategies of hydrogel-based cancer vaccines, and provides some insights into the future development of hydrogel-based cancer vaccines.

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Section: Strategies For Hydrogel-based Cancer Vaccine To Initiate An ...mentioning

confidence: 99%

Hydrogel-guided strategies to stimulate an effective immune response for vaccine-based cancer immunotherapy

et al. 2022

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“…Unlike immunosuppressive adenosine, inosine is an alternative energy source for effector T cells and supplements the energy supply of T cells in a glucose-deficient microenvironment to prevent T cell nutrient depletion ( 44 ). Therefore, synergistic transport of ADA with ICD-inducing drugs reduces the accumulation of adenosine in the TMEs and achieves cascade amplification of ATP-activated antitumor immunity ( 40 ). As Zhao et al reported, the injectable hydrogel composed of sodium alginate, ADA, DOX, and autophagy inducer was constructed ( 40 ).…”

Section: Targeting Adenosine Based On Biomaterials For Cancer Immunot...mentioning

confidence: 99%

“…Therefore, synergistic transport of ADA with ICD-inducing drugs reduces the accumulation of adenosine in the TMEs and achieves cascade amplification of ATP-activated antitumor immunity ( 40 ). As Zhao et al reported, the injectable hydrogel composed of sodium alginate, ADA, DOX, and autophagy inducer was constructed ( 40 ). Sodium alginate was chelated with calcium ions enriched in the TMEs to form an in situ hydrogel.…”

Section: Targeting Adenosine Based On Biomaterials For Cancer Immunot...mentioning

confidence: 99%

Immunosuppressive adenosine-targeted biomaterials for emerging cancer immunotherapy

Zhang

Zhao

et al. 2022

Front. Immunol.

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Immunotherapy has paved the way for the future of cancer therapy, but there are still significant challenges to be overcome, such as the occurrence of immune escape or suppression. Adenosine is essential in modulating the immune responses of immune cells and maintaining immune tolerance. Emerging adenosine pathway inhibitors are considered a breakthrough in cancer immunotherapy, with emphasis first being placed on the top-down blockade of adenosine signaling axis, followed by combination therapy. However, these therapeutic strategies rely on adenosine inhibitors, mainly small molecules or antibody proteins, which are limited by a single route of administration and off-target toxicity. Therefore, synergistic nanomedicine with accurate delivery targeting deeper tumors is focused on in preclinical studies. This review discusses how adenosine reshapes immunosuppressive microenvironments through its effects on immune cells, including lymphocytes and myeloid cells. Additionally, it will be the first discussion of a comprehensive strategy of biomaterials in modulating the adenosine signaling pathway, including inhibition of adenosine production, inhibition of adenosine binding to immune cells, and depletion of adenosine in the microenvironments. Furthermore, biomaterials integrating multiple therapeutic modalities with adenosine blocking are also discussed as a promising strategy for promoting cancer immunotherapy.

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“…PC cells undergo a metabolic switch from oxidative phosphorylation to glycolysis, causing them to synthesize adenosine triphosphate (ATP) from glucose via glycolysis without oxygen [ 34 ]. It has been reported that the relationship between energy metabolism and autophagy creates a relationship between autophagic activity and cellular ATP levels [ 35 , 36 ]. However, inhibition of ATP production via carbon source deprivation or ATP synthesis perturbation suppresses autophagic activity [ 37 ].…”

Section: Molecular Pathway Of the Autophagy Processmentioning

confidence: 99%

Therapeutic Aspects and Molecular Targets of Autophagy to Control Pancreatic Cancer Management

et al. 2022

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Pancreatic cancer (PC) begins within the organ of the pancreas, which produces digestive enzymes, and is one of the formidable cancers for which appropriate treatment strategies are urgently needed. Autophagy occurs in the many chambers of PC tissue, including cancer cells, cancer-related fibroblasts, and immune cells, and can be fine-tuned by various promotive and suppressive signals. Consequently, the impacts of autophagy on pancreatic carcinogenesis and progression depend greatly on its stage and conditions. Autophagy inhibits the progress of preneoplastic damage during the initial phase. However, autophagy encourages tumor formation during the development phase. Several studies have reported that both a tumor-promoting and a tumor-suppressing function of autophagy in cancer that is likely cell-type dependent. However, autophagy is dispensable for pancreatic ductal adenocarcinoma (PDAC) growth, and clinical trials with autophagy inhibitors, either alone or in combination with other therapies, have had limited success. Autophagy’s dual mode of action makes it therapeutically challenging despite autophagy inhibitors providing increased longevity in medical studies, highlighting the need for a more rigorous review of current findings and more precise targeting strategies. Indeed, the role of autophagy in PC is complicated, and numerous factors must be considered when transitioning from bench to bedside. In this review, we summarize the evidence for the tumorigenic and protective role of autophagy in PC tumorigenesis and describe recent advances in the understanding of how autophagy may be regulated and controlled in PDAC.

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An Injectable Hydrogel Reshaping Adenosinergic Axis for Cancer Therapy

Cited by 31 publications

References 29 publications

Hydrogel-guided strategies to stimulate an effective immune response for vaccine-based cancer immunotherapy

Hydrogel-guided strategies to stimulate an effective immune response for vaccine-based cancer immunotherapy

Immunosuppressive adenosine-targeted biomaterials for emerging cancer immunotherapy

Therapeutic Aspects and Molecular Targets of Autophagy to Control Pancreatic Cancer Management

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