Developing oxygen-controlling strategies to boost vaccine immunity and understand hypoxic tumor responses DOI Open Access
Zachary J. Rogers

Published: Jan. 1, 2023

Oxygen (O2) concentration is important in both physiological and pathophysiological contexts. Modulating O2 vivo vitro challenging, yet has vast therapeutic potential necessary to accurately recapitulate environments, respectively. Herein, we developed O2-controlling strategies (i) boost vaccine immunogenicity, (ii) model tumor microenvironments vitro, (iii) understand cancer cell responses different low tensions. Using O2-generating cryogels (injectable, macroporous hydrogels), was used as an adjuvant immunogenicity protect against SARS-CoV-2. In mice, cryogel vaccines (O2-CryogelVAX) induced higher titers of neutralizing antibodies compared bolus (CryogelVAX), O2-CryogelVAX also increased B expansion draining lymph nodes (dLNs) IgG1 titer, suggesting that traveled the dLNs promoted germinal center formation. IgG sublcass cytokine characterization suggest generated a balanced Th1/Th2-mediated immune response without any signs allergic response. Our data represent promising platform increase context infectious disease.O2-controlled culture biological research method. One major use case study hypoxia, or O2. Widespread adoption this technique mitigated by cost, laboratory space requirements, technical challenges, rapid reoxygenation cultures. As alternative, hypothesized immobilizing glucose oxidase (GOX) catalase (CAT) matrices could simultaneously extracellular matrix (ECM) hypoxic environments vitro. After optimizing hypoxia-inducing (HIC) manufacturing process formulation, demonstrate HICs induce hypoxia (1% O2) for 11 days culture, with minimal hydrogen peroxide (H2O2) production consumption. future work, are utilized better dendritic polarization T interactions demonstrating their ability mimic microenvironment (TME). developing new method measure pericellular tension (i.e., cells experience) O2-controlled discovered physioxic (5% setpoints regularly anoxic (0% tensions adherent suspension Electron transport chain inhibition ablates effect, indicating cellular consumption driving factor. RNA-seq revealed primary human hepatocytes cultured physioxia experience ischemia-reperfusion injury due exposure followed reoxygenation. To relationship between incubator gas phase tensions, reaction-diffusion predicts priori. This effect greatest smaller volume vessels (e.g., 96-well plate). By controlling MCF7 have stronger glycolytic glutamine metabolism anoxia vs. hypoxia. expressed levels HIF2A, CD73, NDUFA4L2, etc. lower HIF1A, CA9, VEGFA, anoxia. Proteomics 4T1 had upregulated epithelial-to-mesenchymal transition (EMT) downregulated reactive oxygen species (ROS) management, glycolysis, fatty acid pathways Collectively, these results reveal breast respond non-monotonically O2, not suitable We atmospheric incubators insufficient control introduce concept culture. several modeling tissues physiologically, underpinning importance --Author's abstract

Language: Английский

Progress in ATRP-derived materials for biomedical applications DOI Creative Commons
Mohsen Khodadadi Yazdi,

Payam Zarrintaj,

Mohammad Reza Saeb

et al.

Progress in Materials Science, Journal Year: 2024, Volume and Issue: 143, P. 101248 - 101248

Published: Feb. 11, 2024

Language: Английский

Citations

19
Tailor-Made Polysaccharides for Biomedical Applications DOI Creative Commons
Mohsen Khodadadi Yazdi, Farzad Seidi, Aleksander Hejna

et al.

ACS Applied Bio Materials, Journal Year: 2024, Volume and Issue: 7(7), P. 4193 - 4230

Published: July 3, 2024

Polysaccharides (PSAs) are carbohydrate-based macromolecules widely used in the biomedical field, either their pure form or blends/nanocomposites with other materials. The relationship between structure, properties, and functions has inspired scientists to design multifunctional PSAs for various applications by incorporating unique molecular structures targeted bulk properties. Multiple strategies, such as conjugation, grafting, cross-linking, functionalization, have been explored control mechanical electrical conductivity, hydrophilicity, degradability, rheological features, stimuli-responsiveness. For instance, custom-made known worldwide tissue engineering, drug/gene delivery, regenerative medicine. Furthermore, remarkable advancements supramolecular engineering chemistry paved way mission-oriented biomaterial synthesis fabrication of customized biomaterials. These materials can synergistically combine benefits biology tackle important questions. Herein, we categorize summarize based on methods, explore main strategies customize chemical structures. We then highlight properties using practical examples. Lastly, thoroughly describe tailor-made PSAs, along current existing challenges potential future directions.

Language: Английский

Citations

9
Controlling Pericellular Oxygen Tension in Cell Culture Reveals Distinct Breast Cancer Responses to Low Oxygen Tensions DOI Creative Commons
Zachary J. Rogers, Thibault Colombani, Saad Khan

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(30)

Published: June 14, 2024

In oxygen (O

Language: Английский

Citations

7
Hypoxia‐activated ADCC‐enhanced humanized anti‐CD147 antibody for liver cancer imaging and targeted therapy with improved selectivity DOI Creative Commons

Fangzheng Qi,

Huishan Su,

Bo Wang

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(3)

Published: March 1, 2024

Abstract Therapeutic antibodies (Abs) improve the clinical outcome of cancer patients. However, on‐target off‐tumor toxicity limits Ab‐based therapeutics. Cluster differentiation 147 (CD147) is a tumor‐associated membrane antigen overexpressed in cells. drugs targeting CD147 have achieved inadequate benefits for liver due to side effects. Here, by using glycoengineering and hypoxia‐activation strategies, we developed conditional Ab‐dependent cellular cytotoxicity (ADCC)‐enhanced humanized anti‐CD147 Ab, HcHAb18‐azo‐PEG 5000 (HAP18). Afucosylated ADCC‐enhanced HcHAb18 Ab was produced fed‐batch cell culture system. Azobenzene (Azo)‐linked PEG conjugation endowed HAP18 with features hypoxia‐responsive delivery selective targeting. potently inhibits migration, invasion, matrix metalloproteinase secretion, triggers apoptosis cells, induces ADCC, complement‐dependent cytotoxicity, phagocytosis under hypoxia. In xenograft mouse models, selectively targets hypoxic tissues but not normal organs or tissues, has potent tumor‐inhibiting caused negligible effects exhibited superior pharmacokinetics compared those parent Ab. The hypoxia‐activated safely confers therapeutic efficacy against improved selectivity. This study highlights that hypoxia activation promising strategy improving tumor potential drugs.

Language: Английский

Citations

4
How oxygenation shapes immune responses: emerging roles for physioxia and pathological hypoxia DOI
Ananda S. Mirchandani, Manuel A. Sánchez-García, Sarah R. Walmsley

et al.

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 30, 2024

Language: Английский

Citations

4
Breaking barriers: Smart vaccine platforms for cancer immunomodulation DOI Creative Commons
Mohammad Mahmoudi Gomari,

Taha Ghantabpour,

Nima Pourgholamamiji

et al.

Cancer Communications, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Abstract Despite significant advancements in cancer treatment, current therapies often fail to completely eradicate malignant cells. This shortfall underscores the urgent need explore alternative approaches such as vaccines. Leveraging immune system's natural ability target and kill cells holds great therapeutic potential. However, development of vaccines is hindered by several challenges, including low stability, inadequate response activation, immunosuppressive tumor microenvironment, which limit their efficacy. Recent progress various fields, click chemistry, nanotechnology, exosome engineering, neoantigen design, offer innovative solutions these challenges. These achievements have led emergence smart vaccine platforms (SVPs), integrate protective carriers for messenger ribonucleic acid (mRNA) with functionalization strategies optimize targeted delivery. Click chemistry further enhances SVP performance improving encapsulation mRNA antigens facilitating precise delivery review highlights latest developments technologies therapy, exploring both opportunities challenges advancing transformative approaches.

Language: Английский

Citations

0
Polymer oxidation: A strategy for the controlled degradation of injectable cryogels DOI Creative Commons

Alexandra Nukovic,

Mohammad Hamrangsekachaee,

Mahalakshmi Rajkumar

et al.

Materials Today Bio, Journal Year: 2025, Volume and Issue: unknown, P. 101743 - 101743

Published: April 1, 2025

Language: Английский

Citations

0
HIF-stabilizing biomaterials: from hypoxia-mimicking to hypoxia-inducing DOI Creative Commons
Thibault Colombani, Khushbu Bhatt, Boris Epel

et al.

Materials Advances, Journal Year: 2023, Volume and Issue: 4(15), P. 3084 - 3090

Published: Jan. 1, 2023

Breakthroughs in biomaterials science have paved the way for significant advancements stabilization of hypoxia-inducible factor-α (HIF-α). This approach holds exciting prospects therapeutic use cellular responses to low oxygen.

Language: Английский

Citations

5
Biomaterial-assisted local oxygenation safeguards the prostimulatory phenotype and functions of human dendritic cells in hypoxia DOI Creative Commons
Khushbu Bhatt,

Alexandra Nukovic,

Thibault Colombani

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Dec. 7, 2023

Dendritic cells (DCs), professional antigen-presenting cells, function as sentinels of the immune system. DCs initiate and fine-tune adaptive responses by presenting antigenic peptides to B T lymphocytes mount an effective response against cancer pathogens. However, hypoxia, a condition characterized low oxygen (O 2 ) tension in different tissues, significantly impacts DC functions, including antigen uptake, activation maturation, migration, well T-cell priming proliferation. In this study, we employed O -releasing biomaterials -cryogels) study effect localized supply on human phenotype functions. Our results indicate that -cryogels effectively mitigate exposure hypoxia under hypoxic conditions. Additionally, counteract hypoxia-induced inhibition uptake migratory activity through release hyaluronic acid (HA) mediated mechanisms. Furthermore, preserve restore maturation co-stimulation markers, HLA-DR, CD86, CD40, along with secretion proinflammatory cytokines Finally, our findings demonstrate supplemental released from cryogels preserves DC-mediated priming, ultimately leading proliferation allogeneic CD3+ cells. This work emphasizes potential local oxygenation powerful immunomodulatory agent improve functions offering new approaches for infectious disease treatments.

Language: Английский

Citations

4
Controlling pericellular oxygen tension in cell culture reveals distinct breast cancer responses to low oxygen tensions DOI Creative Commons
Zachary J. Rogers, Thibault Colombani, Saad Khan

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 3, 2023

Oxygen (O

Language: Английский

Citations

2