Polymer-loaded hydrogels serve as depots for lactate and mimic “cold” tumor microenvironments

Allen, Riley; Ivtchenko, Emilie; Thuamsang, Bhasirie; Sangsuwan, Rapeepat; Lewis, Jamal S.

doi:10.1039/d0bm01196g

Cited by 9 publications

(5 citation statements)

References 58 publications

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“…The glycolysis-dominant metabolism is a well-defined hallmark in malignant cells and glycolysis is shown to inactivate the immune cell activity causing an immune "cold" status 55,56 . However, it has been unclear if such a glycolysis-dominant pathway could be rewired or replaced by a high energy output metabolism in tumor cells that are capable of surviving genotoxic anticancer modalities including radiation.…”

Section: Discussionmentioning

confidence: 99%

Fatty acid oxidation fuels glioblastoma radioresistance with CD47-mediated immune evasion

et al. 2022

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Glioblastoma multiforme (GBM) remains the top challenge to radiotherapy with only 25% one-year survival after diagnosis. Here, we reveal that co-enhancement of mitochondrial fatty acid oxidation (FAO) enzymes (CPT1A, CPT2 and ACAD9) and immune checkpoint CD47 is dominant in recurrent GBM patients with poor prognosis. A glycolysis-to-FAO metabolic rewiring is associated with CD47 anti-phagocytosis in radioresistant GBM cells and regrown GBM after radiation in syngeneic mice. Inhibition of FAO by CPT1 inhibitor etomoxir or CRISPR-generated CPT1A−/−, CPT2−/−, ACAD9−/− cells demonstrate that FAO-derived acetyl-CoA upregulates CD47 transcription via NF-κB/RelA acetylation. Blocking FAO impairs tumor growth and reduces CD47 anti-phagocytosis. Etomoxir combined with anti-CD47 antibody synergizes radiation control of regrown tumors with boosted macrophage phagocytosis. These results demonstrate that enhanced fat acid metabolism promotes aggressive growth of GBM with CD47-mediated immune evasion. The FAO-CD47 axis may be targeted to improve GBM control by eliminating the radioresistant phagocytosis-proofing tumor cells in GBM radioimmunotherapy.

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Section: Discussionmentioning

confidence: 99%

Fatty acid oxidation fuels glioblastoma radioresistance with CD47-mediated immune evasion

et al. 2022

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“…The results indicated that lactate accumulation in the hydrogel was comparable to the concentration observed in different tumor types. Furthermore, the infiltrating immune cells in the hydrogel loaded with lactide-based polysulfonic acid mucopolysaccharide showed a high degree of immunosuppression at 7 days (38). In summary, this TMEmimicking hydrogel system exhibits the potential for further exploring immune response based on systems biology.…”

Section: Application In Oncologymentioning

confidence: 86%

Narrative review of gene modification: applications in three-dimensional (3D) bioprinting

Fu¹,

Shen²,

Chen³

et al. 2021

Ann Transl Med

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Objective: This article focused on the application scenarios of three-dimensional (3D) bioprinting and gene-editing technology in various medical fields, including gene therapy, tissue engineering, tumor microenvironment simulation, tumor model construction, cancer regulation and expression, osteogenesis, and skin and vascular regeneration, and summarizing its development prospects and shortcomings.Background: 3D bioprinting is a process based on additive manufacturing that uses biological materials as the microenvironment living cells. The scaffolds and carriers manufactured by 3D bioprinting technology provide a safe, efficient, and economical platform for genes, cells, and biomolecules. Gene modification refers to replacing, splicing, silencing, editing, controlling or inactivating genes and delivering new genes.The combination of this technology that changes cell function or cell fate or corrects endogenous mutations and 3D bioprinting technology has been widely used in various medical field.Methods: We conducted a literature search for papers published up to March 2021 on the gene modification combined with 3D bioprinting in various medical fields via PubMed, Web of Science, China National Knowledge Infrastructure (CNKI). The following medical subject heading terms were included for a MEDLINE search: "3D printing/gene editing", "3D printing/genetic modification", "3D printing/seed cell", "bioprinting/gene editing", "bioprinting/genetic modification", "bioprinting/seed cell", "scaffold/gene editing", "scaffold/genetic modification", "scaffold/seed cell", "gene/scaffold", "gene/bioprinting", "gene/3D printing". Quantitative and qualitative data was extracted through interpretation of each article. Conclusions:We have reviewed the application scenarios of 3D bioprinting and gene-editing technology in various medical fields, it provides an efficient and accurate delivery system for personalized tumor therapy, enhancing the targeting effect while maintaining the integrity of the fabricated structure. It exhibits significant application potential in developing tumor drugs. In addition, scaffolds obtained via 3D bioprinting provide gene therapy applications for skin and bone healing and repair and inducing stem cell differentiation.It also considers the future development direction in this field, such as the emergence and development of

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“…This examination presents increased negative and positive charged areas within the optimized configuration. The charge values were dispersed throughout the entire molecule because the π-electron systems, heteroatoms, and highly active functional groups primarily contribute to the charge distribution 26,27 . Furthermore, the polar architecture affects the charge dispersion.…”

Section: Quantum Chemical Analysismentioning

confidence: 99%

Polymerization of Acrylamide N-methylene Lactic and Glycolic Acid

Khazratkulova,

Zokirova,

Mukhamedova

et al. 2023

Baghdad Sci.J

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In this research work, the novel polymer base on acrylamide N-methylene lactic and glycolic acid was synthesized and its structural performances were identified by the IR, 1H NMR and 13C NMR spectroscopic investigations. The influencing factors and kinetics of polymerization, viscosity performance were studied and quantum chemical calculations were used to identify the correlation between the structure and properties. It was determined that the polymerization rate of the examined monomers in an aqueous solution, in the presence of DAA, adheres to the standard rules for radical polymerization of acrylamide monomers in solution. An investigation into the pH solution's impact on the kinetics of radical polymerization of acrylamido-N-methylene glycolic and acrylamido-N-methylene lactic acids revealed an extreme dependence with a minimum in a neutral medium. It was found the linear correlation between pH and viscosity. The physical and chemical performance of this polymer depends on the structural parameters related the results of quantum chemical calculation. Biological tests conducted on polyacrylamido-N-methylene lactic acid indicated its potential as a plant growth stimulator. The polymeric form of lactic acid was found to enhance the growth of Dustlik variety wheat seedlings by 40% more efficiently than lactic acid alone.

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Polymer-loaded hydrogels serve as depots for lactate and mimic “cold” tumor microenvironments

Abstract: Peptide hydrogels loaded with granulocyte-macrophage colony stimulating factor and poly-(lactic-co-glycolic acid) microparticles can recapitulate lactate concentrations and the immunosuppressive nature of the tumor microenvironment.

Cited by 9 publications

References 58 publications

Fatty acid oxidation fuels glioblastoma radioresistance with CD47-mediated immune evasion

Fatty acid oxidation fuels glioblastoma radioresistance with CD47-mediated immune evasion

Narrative review of gene modification: applications in three-dimensional (3D) bioprinting

Polymerization of Acrylamide N-methylene Lactic and Glycolic Acid

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