Therapeutic Technologies Research Articles

ПЕДАГОГІЧНА БІБЛІОТЕРАПІЯ У ПРОФЕСІЙНІЙ ПІДГОТОВЦІ МАЙБУТНІХ УЧИТЕЛІВ ПОЧАТКОВИХ КЛАСІВ

The article emphasizes the importance of improving the professional training of future primary school teachers, who will be able to qualitatively implement new technologies, methods, forms, and tools in their professional activities. Pedagogical bibliotherapy is analyzed as a component of professional training of future primary school teachers. In psychological and pedagogical science, pedagogical bibliotherapy is considered as a field of knowledge that contributes to the creation of a psychologically comfortable educational environment in which an optimistic attitude towards the world is formed in elementary school students. The essence of the concept of «pedagogical bibliotherapy» is specified and it is emphasized that it performs not only the role of psychological support and rehabilitation, but also a pedagogical one. Attention is focused on the fact that pedagogical bibliotherapy is the latest therapeutic technology in the educational process, which contributes to the harmonization of the emotional, spiritual and intellectual spheres of the student's personality. In the conditions of the war, the problem of introducing the means of pedagogical bibliotherapy into the teacher's professional activity is particularly relevant, therefore, it should occupy an important place in the professional training of future primary school teachers. It is noted that the means of pedagogical bibliotherapy should be used to optimize the educational process, as they help to develop students’ activity, sociability, creativity, satisfy their cognitive needs, and form self-determination and self-organization skills. The main means of pedagogic bibliopedagogy, which are expedient to use in the pedagogical activities of elementary school teachers, are highlighted, in particular: formal-content, genre-content, and educational-integration esthetic therapy technologies of personal influence.

РОЛЬ КОЛЬОРУ В ОСМИСЛЕННІ ПІДЛІТКАМИ ВЛАСНОГО ЕМОЦІЙНОГО КОНТЕКСТУ ТА ЙОГО ЗМІН ПІД ВПЛИВОМ ПСИХОТРАВМУЮЧИХ ОБСТАВИН

The article deals with using art therapeutic technologies to comprehend adolescents’ emotional context. Fragments of psychoanalytic work using artistic and symbolic images are presented. The paper analyzes a set of thematic drawings covering various aspects of adolescents’ lives and attitudes towards themselves, others, and the world around them. The results of an experimental study are given. It is noted that the art therapy method contains the potential to actualize the strategy of creative activity and is based on the expressive arts that provide support for the individual. It has been found that using color in art therapy techniques corrects disorders of psychosomatic and psycho-emotional processes in personal development. The role of color in adolescents’ comprehension of their emotional context and its changes under the influence of psychotraumatic circumstances is considered. It is stated that the use of mandalas allows a teenager to delve into the unconscious levels of the psyche and ensure its balance and integrity under of the influence psychotraumatic circumstances It is proved that color not only affects an adolescent’s personality depending on his or her emotional state but also shapes emotions in a certain way. The art therapy method has been found to contribute to the subject’s reflexive comprehension of his/her emotional experiences embodied in artistic and symbolic forms

Advanced Preparation Methods and Biomedical Applications of Single-Atom Nanozymes.

Metal nanoparticles with inherent defects can harness biomolecules to catalyze reactions within living organisms, thereby accelerating the advancement of multifunctional diagnostic and therapeutic technologies. In the quest for superior catalytic efficiency and selectivity, atomically dispersed single-atom nanozymes (SANzymes) have garnered significant interest recently. This review concentrates on the development of SANzymes, addressing potential challenges such as fabrication strategies, surface engineering, and structural characteristics. Notably, we elucidate the catalytic mechanisms behind some key reactions to facilitate the biomedical application of SANzymes. The diverse biomedical uses of SANzymes including in cancer therapy, wound disinfection, biosensing, and oxidative stress cytoprotection are comprehensively summarized, revealing the link between material structure and catalytic performance. Lastly, we explore the future prospects of SANzymes in biomedical fields.

The role of neuropeptides in cutaneous wound healing: a focus on mechanisms and neuropeptide-derived treatments.

An extensive network of cutaneous nerves, neuropeptides, and specific receptors richly innervates the skin and influences a variety of physiological and pathological processes. The sensory and autonomic nerve fibers secrete a variety of neuropeptides that are essential to the different phases of wound healing. In addition to initiating a neurogenic inflammatory response in the early stages of healing, neuropeptides also control wound healing by influencing immune cells, repair cells, and the growth factor network. However, the precise mechanism by which they accomplish these roles in the context of cutaneous wound healing is still unknown. Investigating the mechanisms of action of neuropeptides in wound healing and potential therapeutic applications is therefore urgently necessary. The present review discusses the process of wound healing, types of neuropeptides, potential mechanisms underlying the role of neuropeptides in cutaneous wound healing, as well as some neuropeptide-derived treatment strategies, such as hydrogels, new dressings, electro stimulation, and skin-derived precursors. Future in-depth mechanistic studies of neuropeptides in cutaneous wound healing may provide opportunities to develop therapeutic technologies that harness the roles of neuropeptides in the wound healing process.

Transforming Lung Cancer Care: The Role of Transferosomes in Modern Drug Delivery.

Cancer stands as one of the leading causes of death worldwide, and lung cancer represents its most aggressive and persistent form. Traditional strategies for addressing lung cancer involve various medical therapies such as radiotherapy, chemotherapy, and surgical excision. Despite their prevalence, these conventional methods lack precision and inadvert-ently cause collateral damage to neighboring healthy cells. Recently, nanotechnology has emerged as a potential strategy for the treatment and management of lung carcinomas, bring-ing about a transformative shift in existing approaches. The primary focus of this shift is on minimizing harmful effects and improving the bioavailability of chemotherapy drugs specif-ically targeted at tumour cells. Currently, transferosome nanocarrier systems are widely em-ployed to overcome the obstacles presented by lung cancer. The utilization of transferosome-loaded therapeutic medication administration technology holds tremendous potential in reg-ulating tumour cell growth and treating lung cancer. The purpose of this study is to provide an overview and analysis of current advancements in transferosome-based drug delivery sys-tems, employing inhalational nanoparticle strategies for precise drug targeting in lung cancer management.

The Application of CRISPR/Cas9 in Cancer Immunotherapy

Currently, Cancer is the number one killer of human health. The death rate from cancer is increasing year over year as the population ages and grows, particularly since 2019, when there were almost 10 million cases globally recorded by the World Health Organization every year. In light of this trend, it is imperative to continue developing medications and to update and iterate on anti-cancer therapeutic technologies. CAR-T cell therapy, microphage-based therapy, oncolytic virotherapy, and checkpoint blockade therapy are the most popular cancer treatments, but a few patients still cannot tolerate these therapies. A post-optimized strategy is to use gene editing to alter the characteristics of cancer treatment. New therapeutic options for the treatment of complex disorders have become available with the development of CRISPR/Cas9 gene editing technology in recent years. This method is widely used in market research for gene knockdown, endogenous gene expression, and chromosome locus markers because of its accuracy and efficiency in processing harmful gene fragments. Also, it is extremely valuable from a medical standpoint when researching immunomodulator resistance. Despite its great potential, there remain concerns over the technology’s usefulness and efficacy and negative prognostic reactions. This review primarily focuses on the current use of CRISPR/Cas9 in cancer immunotherapies.

Crystallite size and phase purity in Pb1-xSrxTiO3 ferroelectric perovskites for biomedical applications via controlled sintering

ABSTRACT Lead strontium titanate (Pb1-xSrx)TiO3 (PST) is a ferroelectric perovskite material with tunable properties, including Curie temperature, spontaneous polarization, and high dielectric permittivity, making it promising for advanced biomedical applications, such as biosensors, bioimaging, and light-activated therapeutics. This study investigates the effect of varying sintering temperatures on the crystallite size and phase purity of PST, aiming to optimize its performance for biomedical devices. PbCO3, SrCO3, and TiO2 powders were processed via ball milling for 58 hours, followed by sintering at temperatures ranging from 500°C to 1100°C. Laser diffraction particle size analysis and X-ray diffraction (XRD) were used to assess the particle size and crystal phase transformations. The results demonstrate that higher sintering temperatures improve the PST phase composition, reducing impurities and enhancing crystallite growth. The most significant crystal growth was observed at 900°C, while the optimal phase purity and crystallite size (91.5 nm) were achieved at 1100°C, producing 100% single-phase PST. These findings emphasize the critical role of sintering temperature in tailoring PST’s properties, enhancing its suitability for electronic and microelectronic biomedical devices. Controlled sintering in perovskite materials opens new pathways for their application in medical diagnostics and therapeutic technologies.

Aggregation-induced emission luminogens for intracellular bacteria imaging and elimination

Intracellular bacterial infections are a serious threat to human health due to their ability to escape immunity and develop drug resistance. Recent attention has been devoted to identifying and ablating intracellular bacteria with fluorescence probes. Aggregation-induced emission luminogens (AIEgens) photosensitizers as fluorescence probes possess excellent photostability and rapid response, which have emerged as powerful fluorescent tools for intracellular bacterial detection and antibacterial therapy. This review is intended to highlight the current advances in AIEgens on intracellular bacteria imaging and elimination, which covers topics from intracellular AIE mechanism, intracellular bacteria imaging of AIEgens to the elimination of intracellular bacteria with AIEgens. AIEgens utilized different interactions to detect intracellular bacteria, emitting bright light due to restricted intramolecular movement to visualize intracellular bacteria. Photosensitive AIEgens generate reactive oxygen species (ROS) in the aggregate state to elimate intracellular bacteria. Moreover, the prospects and application of AIEgens in intracellular bacteria imaging and elimination are also discussed, which provides insights for the development of AIE-based diagnostic and therapeutic materials and technologies.

Blood MAIT cells phenotype in patients with Opisthorchis felineus invasion depending on the severity of liver fibrosis

Introduction. MAIT cells are a new subpopulation of T cells that protect mucous barriers against penetration of foreign substances. There are practically no studies devoted to the participation of these cells in the pathogenesis of parasitic diseases.Aim. To study the phenotype of blood MAIT cells in patients with Opisthorchis felineus (O. felineus) invasion depending on the severity of liver fibrosis.Materials and methods. A total of 78 patients with O. felineus invasion (42 men and 36 women) and 26 control group individuals (14 men and 12 women) were examined. Opisthorchiasis was diagnosed using coproovoscopy and duodenal contents microscopy. All patients underwent liver elastometry using Aixplorer (France) or Siemens Acuson S2000 (Germany) systems with determination of the liver fibrosis degree according to METAVIR. The phenotype composition of lymphocytes was investigated using a Navios flow cytometer (Beckman Coulter, USA). T cells, T helpers, and T cytotoxic lymphocytes were isolated and the presence of NCR Va7.2 and CD161 on the surface of these cells was assessed.Results. The content of MAIT T-helpers was decreased in patients with O. felineus invasion compared to healthy individuals (p < 0.001). In MAIT T-cytotoxic cells, a similar pattern was not detected (p = 0.5). In patients with liver fibrosis F2 according to METAVIR compared to individuals with F0 according to METAVIR, a decrease in the total number of T-cells, T-helpers and T-cytotoxic cells, as well as MAIT T-helpers and MAIT T-cytotoxic cells was observed. Thus, the content of CD161+ NCR Va7.2+ T-helpers was 0.020% [0.004–0.042%] in patients with opisthorchiasis with F0 according to METAVIR and 0.0% [0.0–0.003%] in individuals with liver fibrosis F2 according to METAVIR (p = 0.001). For CD161+ NCR Va7.2+ T-cytotoxic cells, these indicators were, respectively, 1.47% [0.41–2.49%] and 0.12% [0.07–0.31%] (p < 0.001).Conclusion. Further study of MAIT cells in patients with liver pathology has undoubted prospects for the creation of new therapeutic and diagnostic technologies.

Overview of Venous Thromboembolism and Emerging Therapeutic Technologies Based on Nanocarriers-Mediated Drug Delivery Systems

Venous thromboembolism (VTE) is a serious health condition and represents an important cause of morbidity and, in some cases, mortality due to the lack of effective treatment options. According to the Centers for Disease Control and Prevention, 3 out of 10 people with VTE will have recurrence of a clotting event within ten years, presenting a significant unmet medical need. For some VTE patients, symptoms can last longer and have a higher than average risk of serious complications; in contrast, others may experience complications arising from insufficient therapies. People with VTE are initially treated with anticoagulants to prevent conditions such as stroke and to reduce the recurrence of VTE. However, thrombolytic therapy is used for people with pulmonary embolism (PE) experiencing low blood pressure or in severe cases of DVT. New drugs are under development, with the aim to ensure they are safe and effective, and may provide an additional option for the treatment of VTE. In this review, we summarize all ongoing trials evaluating anticoagulant interventions in VTE listed in clinicaltrials.gov, clarifying their underlying mechanisms and evaluating whether they prevent the progression of DVT to PE and recurrence of thrombosis. Moreover, this review summarizes the available evidence that supports the use of antiplatelet therapy for VTE. Since thrombolytic agents would cause off-target effects, targeted drug delivery platforms are used to develop various therapeutics for thrombotic diseases. We discuss the recent advances achieved with thrombus-targeting nanocarriers as well as the major challenges associated with the use of nanoparticle-based therapeutics.

Multi-modal networks for real-time monitoring of intracranial acoustic field during transcranial focused ultrasound therapy

Background and objective:Transcranial focused ultrasound (tFUS) is an emerging non-invasive therapeutic technology that offers new brain stimulation modality. Precise localization of the acoustic focus to the desired brain target throughout the procedure is needed to ensure the safety and effectiveness of the treatment, but acoustic distortion caused by the skull poses a challenge. Although computational methods can provide the estimated location and shape of the focus, the computation has not reached sufficient speed for real-time inference, which is demanded in real-world clinical situations. Leveraging the advantages of deep learning, we propose multi-modal networks capable of generating intracranial pressure map in real-time. Methods:The dataset consisted of free-field pressure maps, intracranial pressure maps, medical images, and transducer placements was obtained from 11 human subjects. The free-field and intracranial pressure maps were computed using the k-space method. We developed network models based on convolutional neural networks and the Swin Transformer, featuring a multi-modal encoder and a decoder. Results:Evaluations on foreseen data achieved high focal volume conformity of approximately 93% for both computed tomography (CT) and magnetic resonance (MR) data. For unforeseen data, the networks achieved the focal volume conformity of 88% for CT and 82% for MR. The inference time of the proposed networks was under 0.02 s, indicating the feasibility for real-time simulation. Conclusions:The results indicate that our networks can effectively and precisely perform real-time simulation of the intracranial pressure map during tFUS applications. Our work will enhance the safety and accuracy of treatments, representing significant progress for low-intensity focused ultrasound (LIFU) therapies.

From banked human cord blood to induced pluripotent stem cells: New opportunities and promise in induced pluripotent stem cell banking (Review).

Umbilical cord blood (CB) is a valuable source of haematopoietic stem/progenitor cells (HSCs) and is known for the therapeutic use of these cells in treating blood disorders. However, challenges such as a high running cost and the increasing availability of treatment alternatives have made the effort to sustain CB banks difficult. This prompts the need to revisit the current CB banking initiatives to retain the relevance in this ever‑changing era parallel to the fast‑pacing development of cell‑based therapeutic technology. Cellular reprogramming has shown to have successfully converted adult somatic cells into human induced pluripotent stem cells (hiPSCs), which promise wider applications in regenerative medicine, personalized treatment and tissue engineering. CB is the youngest, primitive adult cell source that has not been affected by any prior, acquired disorders. Hence, using CB as a source of candidate cells for generating hiPSCs may be a new opportunity for banking, albeit with challenges. The present review summarizes the rise and fall of CB usage and banking for clinical therapy, the considerations in reprogramming CB into hiPSCs, the safety concerns regarding the use of hiPSC‑derived cells in clinical transplantation and the prospect of using CB‑derived hiPSCs.

Endonuclease A in Streptococcus pneumoniae: escaping from neutrophil extracellular traps (NETs) and relationship in immunogenicity

Streptococcus pneumoniae (S. pneumoniae), which is a Gram-positive diplococcus, has emerged as a significant human pathogen. It is a primary cause of bacterial pneumonia, otitis media, meningitis, and septicemia, leading to a considerable impact on global morbidity and mortality. The investigation of S. pneumoniae and its virulence factors has resulted in the identification of surface endonuclease A (EndA). EndA functions in DNA uptake during natural transformation and plays a significant role in gene transfer. The ability of S. pneumoniae to degrade neutrophil extracellular traps (NETs) enhances its virulence and invasive potential in pneumococcal infections. NETosis occurs when neutrophils release chromatin into the extracellular space to form NETs, capturing and neutralizing pathogens. Currently, NETosis can be induced by several microbes, particulate matter, and sterile stimuli through distinct cellular mechanisms, and this includes the involvement of EndA in S. pneumoniae. Here, we reviewed the cellular functions of EndA, its role in S. pneumoniae as a virulence factor in relation to NETosis, its relationship to immunogenicity, and its involvement in several diseases. The discovery of this relationship would significantly impact therapeutic technology in reducing disease burden, especially pneumococcal infections.

The Current Treatment for Neurodegenerative Diseases

Neurodegenerative diseases (NDs) refer to dysfunction of central nerve system, characterized by progressive loss of neuronal structure and function, ultimately resulting in decline in patients memory, motor ability, language and intelligence. The typical NDs include age related diseases like Aleimers disease (AD) and genetic diseases such as Huntingtons diseases (HD) and amyotrophic lateral sclerosis (ALS). NDs impose heavy economic burden and suffer to the enormous patients over the world, however, many types of NDs do not have a cure; existing treatments only aim to improve their symptoms. Under that condition, Gene therapy has shown potential for transporting some genetic products into the cells and correct faulty genes. Over the years, research have highlighted the promise of gene therapies using AAV vector in treating NDs. At the same time, a number of emerging therapeutic technologies for neurodegenerative diseases, such as epigenetic interventions through acetylation/deacetylation, gene therapies that target specific mRNAs or non-coding RNAs, and photo biomodulation therapies that can act on brain tissue, are also being studied. In this discussion, we explore the historical, present, and future outlook of gene therapies for neurodegenerative conditions.

Optical investigation of degradation of graphene oxide in alkaline environment: Evidence of two distinct photon-emitting phases in visible region.

In this work we show a procedure of treating of the graphene oxide in alkaline environment as a function of the treatment time in order to obtain novel structures with strong luminescence properties, water-stable, useful as potential replacement for critical raw materials employed as example in optical and optoelectronic devices or for diagnostic and therapeutic technology. These structures have distinct blue and green-luminescence properties which derived most likely from different structural conformations, one associable with that of carbon quantum dots (or as an alternative to that of the Oxidative Debris), the other, lighter and more similar to organic compounds, reported in literature as fulvic-like molecules, but whose nature has to be further investigated. We show that the lighter fraction has a dual mechanism of photoemission: the excitation-independent PL for excitation wavelength within 350 nm and the excitation-dependent component for excitation wavelength ranging in the visible spectrum. The PL dual behaviour could depend on fluorescent nanoclusters composed by specific organic fluorophores with a carbonaceous core. FTIR analysis shows reasonably the same functional groups unless of some difference discussed in the text, meanwhile UV–Vis and PL analysis clearly highlight two distinct emissions (450 nm and 530 nm) in the visible region of the electromagnetic spectrum. Excitation-dependent photoluminescence, water stability and organic fluorescent nanostructures are issues particularly required for application in the biological field but also in materials science.

Microwave Frequency Analysis of Dielectric Properties in Biological Tissues: Insights into Dielectric Constant, Conductivity, and Resistivity at 9.4 GHz

This study investigates the dielectric properties of various biological tissues at microwave frequencies, specifically focusing on their dielectric constant, conductivity, resistivity, and loss tangent. Using methods such as Von Hippel’s and Yadav Gandhi’s techniques, the dielectric characteristics of heart, liver, brain, and muscle of chicken tissues were analysed at 9.4 GHz. It is found that tissues with higher water content exhibit greater dielectric constants and conductivities, while those with higher solid content, like liver, display higher resistivity. It has also been observed that tissues with lower dielectric constants and conductivities are those with greater absorption indices, which are typically associated with increased energy dissipation as heat. An increasing amount of energy dissipation may result from tissues with higher absorption rates being less effective at transferring microwave energy, as suggested by this inverse connection, which also emphasizes the complexity of electromagnetic wave interaction within tissues. This work provides critical insights into the interaction of electromagnetic waves with biological tissues, which is essential for applications in medical diagnostics, therapeutic technologies, and electromagnetic exposure safety standards.

NF-κB-activated oncogene inhibition strategy for cancer gene therapy

NF-κB is a promising target for cancer treatment because of its overactivation in almost all cancers but countless NF-κB inhibitors rarely became clinical drugs due to side effects. In contrast to traditional cancer treatments aimed at inhibiting NF-κB activity, this study develop a novel approach termed HOPE, which focuses on activating the exogenous effector gene CRISPR-Cas13a within cancer cells, achieved by utilizing the NF-κB-specific promoter DMP previously constructed, then targets and suppresses the expression of oncogenes TERT, PLK1, KRAS and MYC at mRNA level. We evaluated the antitumour effects of HOPE in various cultured cells and confirmed it could induce obvious the death of cancer cells without affecting normal cells. By packaging HOPE into adeno-associated virus (AAV) and intravenously injected it to treat mice that were subcutaneously transplanted with colorectal cancer. This validated that rAAV-HOPE could significantly inhibit tumour growth without side effects. Based on the scRNA-seq data, we observed that HOPE could activate the immune system and decrease the proportion of cancer cells, particularly reducing the stemness of cancer cells. This study elucidates an important role of HOPE in inhibiting cancer cell growth both in vitro and in vivo, additionally provides a novel therapeutic technology for cancer gene therapy.

PROTAC-DB 3.0: an updated database of PROTACs with extended pharmacokinetic parameters.

Proteolysis-targeting chimera (PROTAC) is an emerging therapeutic technology that leverages the ubiquitin-proteasome system to target protein degradation. Due to its event-driven mechanistic characteristics, PROTAC has the potential to regulate traditionally non-druggable targets. Recently, AI-aided drug design has accelerated the development of PROTAC drugs. However, the rational design of PROTACs remains a considerable challenge. Here, we present an updated online database, PROTAC-DB 3.0. In this third version, we have expanded the database to include 6111 PROTACs (87% increase compared to the 2.0 version). Additionally, the database now contains 569 warheads (small molecules targeting the protein), 2753 linkers, and 107 E3 ligands (small molecules recruiting E3 ligases). The number of target-PROTAC-E3 ternary complex structures has also increased to 959. Recognizing the importance of druggability in PROTAC design, we have incorporated pharmacokinetic data to PROTAC-DB 3.0. To enhance user experience, we have added features for sorting based on molecular similarity and literature publication date. PROTAC-DB 3.0 is accessible at http://cadd.zju.edu.cn/protacdb/.

Patient-Centric Long-Acting Injectable and Implantable Platforms─An Industrial Perspective.

The increasing focus on patient centricity in the pharmaceutical industry over the past decade and the changing healthcare landscape, driven by factors such as increased access to information, social media, and evolving patient demands, has necessitated a shift toward greater connectivity and understanding of patients' unique treatment needs. One pharmaceutical technology that has supported these efforts is long acting injectables (LAIs), which lower the administration frequency for the patient's provided convenience, better compliance, and hence better therapeutical treatment for the patients. Furthermore, patients with conditions like the human immunodeficiency virus and schizophrenia have positively expressed the desire for less frequent dosing, such as that obtained through LAI formulations. In this work, a comprehensive analysis of marketed LAIs across therapeutic classes and technologies is conducted. The analysis demonstrated an increasing number of new LAIs being brought to the market, recently most as aqueous suspensions and one as a solution, but many other technology platforms were applied as well, in particular, polymeric microspheres and in situ forming gels. The analysis across the technologies provided an insight into to the physicochemical properties the compounds had per technology class as well as knowledge of the excipients typically used within the individual formulation technology. The principle behind the formulation technologies was discussed with respect to the release mechanism, manufacturing approaches, and the possibility of defining predictive in vitro release methods to obtain in vitro in vivo correlations with an industrial angle. The gaps in the field are still numerous, including better systematic formulation and manufacturing investigations to get a better understanding of potential innovations, but also development of new polymers could facilitate the development of additional compounds. The biggest and most important gaps, however, seem to be the development of predictive in vitro dissolution methods utilizing pharmacopoeia described equipment to enable their use for product development and later in the product cycle for quality-based purposes.

Hypoxia-responsive synthetic gene circuits to improve safety and potency of CAR T cell therapy for solid tumors.

37 Background: Engineered cell therapies expressing a chimeric antigen receptor (CAR) in human T cells have demonstrated great promise for the treatment of hematological malignancies. However, unique challenges remain in translating the success of CAR T cell therapies to solid tumors, namely: (1) specificity: there are few truly unique antigens present on solid tumors, leading to off-target effects that damage normal tissue and pose safety risks; and (2) suppression: solid tumors develop microenvironments that are immunosuppressive and decrease T cell survival and tumor-directed cytotoxicity. To address these challenges and improve the safety and potency of solid tumor cell therapy, we engineered cells with synthetic genetic circuits containing a previously validated hypoxia biosensor (HBS) that responds to upregulation of the native HIF1α and HIF2α transcription factors by hypoxia, enabling the cells to sense and respond to the hypoxic tumor microenvironment ubiquitous among solid tumors. Methods: We evaluated CAR expression from circuit architectures containing the HBS promoter driving expression of both CAR and native HIF1α, HIF2α, as well as from circuit architectures containing the HBS promoter and our toolkit of synthetic transcription factors and promoters. Circuits were integrated into HEK293 cells via PiggyBac transposon vector to generate stable cell lines. Cells were subsequently cultured in normoxia (21% O2) and hypoxia (1% O2), and harvested for flow cytometric analysis to evaluate CAR surface expression across a three day time frame. Results: We identified novel circuits providing fast reporter output with minimal background signal under hypoxic conditions, and elucidated design rules that enable or restrict amplification of transgene in native HIF1α and HIF2α-containing circuits. We observed differences in CAR transgene expression in hypoxia between circuits containing HIF1α and HIF2α-mediated feedback, suggesting mechanistic differences in regulation of HIF1α and HIF2α when overexpressed. Additionally, we observed greatly amplified transgene expression in circuit topologies containing feedback mediated by our synthetic transcription factor and promoter toolkit compared to native HIF1α and HIF2α-containing circuits and cells constitutively expressing CAR. Conclusions: We present a new therapeutic technology that senses hypoxic environments and enables high-output sense and respond behaviors with therapeutic outputs. We envision that this technology will enable development of safer, more effective cell therapies for solid tumors, as well as provide new biological and mechanistic insights that can inform the future development of hypoxia-responsive cell therapies.