Glycosylation editing: an innovative therapeutic opportunity in precision oncology.

Cancer is still one of the most arduous challenges in the human society, even though humans have found many ways to try to conquer it. With our incremental understandings on the impact of sugar on human health, the clinical relevance of glycosylation has attracted our attention. The fact that altered glycosylation profiles reflect and define different health statuses provide novel opportunities for cancer diagnosis and therapeutics. By reviewing the mechanisms and critical enzymes involved in protein, lipid and glycosylation, as well as current use of glycosylation for cancer diagnosis and therapeutics, we identify the pivotal connection between glycosylation and cellular redox status and, correspondingly, propose the use of redox modulatory tools such as cold atmospheric plasma (CAP) in cancer control via glycosylation editing. This paper interrogates the clinical relevance of glycosylation on cancer and has the promise to provide new ideas for laboratory practice of cold atmospheric plasma (CAP) and precision oncology therapy.

Cold atmospheric plasma for chronic kidney disease-related skin disorders.

BACKGROUND AND HYPOTHESIS: An estimated 80% of individuals with chronic kidney disease (CKD) experience concomitant skin disorders, yet experimental research that elucidates the pathological changes in CKD-affected skin is limited. Cold atmospheric plasma (CAP) has shown promise in regulating keratinocyte proliferation, skin barrier function, and anti-inflammatory activity. We hypothesize that CAP emerges as a promising therapeutic avenue for CKD-related skin diseases. METHODS: Male and female C57/BL6 mice were administered a 0.2% adenine diet to generate a CKD mouse model. Skin samples from dialysis patients were also collected. These models were used to investigate the pathological alterations in the renal glomeruli, tubules, and epidermis. Subsequently, the potential impact of CAP on the stratum corneum, keratinocytes, skin hydration, and inflammation in mice with CKD were examined. RESULTS: Renal biopsies revealed glomerular and tubular atrophy, epithelial degeneration and necrosis in uriniferous tubules, and significant renal interstitial fibrosis. Skin biopsies from patients with CKD and mice showed stratum corneum thickening, epidermis atrophy, skin hydration dysfunction, and excessive inflammation. CAP attenuated skin atrophy, hydration dysfunction, and inflammation in mice with CKD, as evidenced by the activated level of YAP1/ß-catenin and Nrf-2/OH-1, enhanced expression of K5 and Ki67, increased levels of AQP3, collagen I, and GLUT1, reduced infiltration of CD3+ T cells, and diminished levels of IL-6 and TNF-α. CONCLUSION: This study provides valuable insights into the pathological changes in skin associated with CKD in both patients and animal models. It also establishes that CAP has the potential to effectively mitigate skin atrophy, hydration dysfunction, and inflammation, suggesting a novel therapeutic avenue for the treatment of CKD-related skin disorders.

Cold atmospheric plasma attenuates skin cancer via ROS induced apoptosis.

BACKGROUND: Cold atmospheric plasma (CAP) has been widely used in biomedical research, especially in vitro cancer therapy. Cutaneous squamous cell carcinoma (CSCC) is a malignant tumor originating from epidermal keratinocytes. However, the mechanism of CAP therapy on CSCC remains unclear. METHODS AND RESULTS: The animal models of CSCC induced by 7,12-dimethylbenz(a) anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) were constructed. For the CAP treatment group, after each TPA application, CAP was administered for 3 min twice weekly after drying. HE staining were used to detect the pathological status of tumor tissue in each group. The levels of PCNA, Bcl-2, Bax, MMP2 and MMP9 were evaluated by western blot and qPCR. TUNEL staining were used to detect apoptosis in tumor tissues. In vivo, serum samples were used for ELISA of total ROS. MTT assay was used to detect the viability of A431 cells. Western blot and qPCR were used to detect the levels of PCNA, Bcl-2, Bax, MMP2 and MMP9 in A431 cells. A431 cell proliferation was examined by colony formation assay. The proportions of apoptosis of A431 cells were detected by flow cytometry. Transwell assessed the ability of A431 cells migration and proliferation. We found that CAP could induce skin cancer cells apoptosis and inhibit the progress of skin cancer. Through experiments in vitro, reactive oxygen species (ROS) generated by N-acetylcysteine (NAC) and CAP inhibited the proliferation and migration of A431 skin cancer cells while promoting apoptosis. CONCLUSIONS: These evidences suggest the protective effect of CAP in CSCC, and CAP has the potential clinical application of CSCC.

Cold atmospheric plasma therapy for Malassezia folliculitis: Laboratory investigations and a randomized clinical trial.

BACKGROUND: Current treatment options for Malassezia folliculitis (MF) are limited. Recent research has demonstrated the inhibitory effect of cold atmospheric plasma (CAP) on the growth of Malassezia pachydermatis in vitro, suggesting CAP as a potential therapeutic approach for managing MF. OBJECTIVES: The objective of our study is to assess the in vitro antifungal susceptibility of Malassezia yeasts to CAP. Additionally, we aim to evaluate the efficacy and tolerability of CAP in treating patients with MF. METHODS: We initially studied the antifungal effect of CAP on planktonic and biofilm forms of Malassezia yeasts, using well-established techniques such as zone of inhibition, transmission electron microscopy, colony count assay and 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt assay. Subsequently, a randomized (1:1 ratio), active comparator-controlled, observer-blind study was conducted comparing daily CAP therapy versus itraconazole 200 mg/day for 2 weeks in 50 patients with MF. Efficacy outcomes were measured by success rate, negative microscopy rate and changes in Dermatology Life Quality Index (DLQI) and Global Aesthetic Improvement Scale (GAIS) scores. Safety was assessed by monitoring adverse events (AEs) and local tolerability. RESULTS: In laboratory investigations, CAP time-dependently inhibited the growth of Malassezia yeasts in both planktonic and biofilm forms. Forty-nine patients completed the clinical study. At week 2, success was achieved by 40.0% of subjects in the CAP group versus 58.3% in the itraconazole group (p = 0.199). The negative direct microscopy rates of follicular samples were 56.0% in the CAP group versus 66.7% in the itraconazole group (p = 0.444). No significant differences were found in the proportion of subjects achieving DLQI scores of 0/1 (p = 0.456) or in the GAIS responder rates (p = 0.588) between the two groups. Three patients in the CAP group and one patient in the itraconazole group reported mild AEs. CONCLUSION: CAP demonstrated significant antifungal activity against Malassezia yeasts in vitro and exhibited comparable efficacy to itraconazole in treating MF patients. Without the associated adverse effects of oral antifungal drugs, CAP can be considered a promising and safe treatment modality for MF.

Effect of cold atmospheric plasma on changing of biomolecular structures involved in apoptosis pathways of melanoma cancer.

BACKGROUND: Cold atmospheric plasma (CAP), is a technology based on non-thermal ionized gas that is used for cancer therapy in research. We evaluated the effect of CAP on malignant melanoma cancer cell line (B16) in comparison with normal cells (L929). METHODS: The effect of CAP on the cytotoxicity of B16 and L929 cell lines was assayed by the MTT method and inverted microscopy. The induction of apoptosis in cells was evaluated using a fluorescence microscope. FTIR monitored the CAP effect in biomacromolecules changes in these cell lines. QPCR assayed gene expression of BAX, BCL-2, and Caspase-3 (CASP-3). RESULTS: The results of the MTT test showed CAP has a cytotoxic effect on the B16 cancer cell line more than L929 normal cells (p < 0.0001). The results of invert and fluorescence microscopy showed CAP-induced apoptotic morphology on cancerous cells. FTIR spectroscopy indicated CAP changes biomacromolecules structure. Evaluation of gene expression showed CAP increased BAX and CASP-3 gene expression. Also, it decreased BCL-2 gene expression. CONCLUSIONS: Taken together, CAP may change biomacromolecule structures involved in apoptosis pathways, decrease proliferation and induce apoptosis in cancer cells.

Trident cold atmospheric plasma blocks three cancer survival pathways to overcome therapy resistance.

Therapy resistance is responsible for most cancer-related death and is mediated by the unique ability of cancer cells to leverage metabolic conditions, signaling molecules, redox status, and other pathways for their survival. Interestingly, many cancer survival pathways are susceptible to disturbances in cellular reactive oxygen species (ROS) and may therefore be disrupted by exogenous ROS. Here, we explore whether trident cold atmospheric plasma (Tri-CAP), a gas discharge with exceptionally low-level ROS, could inhibit multiple cancer survival pathways together in a murine cell line model of therapy-resistant chronic myeloid leukemia (CML). We show that Tri-CAP simultaneously disrupts three cancer survival pathways of redox deregulation, glycolysis, and proliferative AKT/mTOR/HIF-1α signaling in this cancer model. Significantly, Tri-CAP blockade induces a very high rate of apoptotic death in CML cell lines and in primary CD34+ hematopoietic stem and progenitor cells from CML patients, both harboring the therapy-resistant T315I mutation. In contrast, nonmalignant controls are minimally affected by Tri-CAP, suggesting it selectively targets resistant cancer cells. We further demonstrate that Tri-CAP elicits similar lethality in human melanoma, breast cancer, and CML cells with disparate, resistant mechanisms and that it both reduces tumor formation in two mouse models and improves survival of tumor-bearing mice. For use in patients, administration of Tri-CAP may be extracorporeal for hematopoietic stem cell transplantation therapy, transdermal, or through its activated solution for infusion therapy. Collectively, our results suggest that Tri-CAP represents a potent strategy for disrupting cancer survival pathways and overcoming therapy resistance in a variety of malignancies.

Exploring the Use of Cold Atmospheric Plasma for Sound and Vibration Generation.

In this study, we investigate the potential of cold atmospheric plasma (CAP) as a non-contact excitation device, comparing its performance with an ultrasound transmitter. Utilizing a scanning Laser Doppler Vibrometer (LDV), we visualize the acoustic wavefront generated by a CAP probe and an ultrasound sensor within a designated 50 mm × 50 mm area in front of each probe. Our focus lies in assessing the applicability of a CAP probe for exciting a small polymethyl methacrylate (PMMA) sample. By adjusting the dimensions of the sample to resonate at the excitation frequency of the probe, we can achieve high vibrational velocities, enabling further mechanical analysis. In contrast with traditional vibration excitation techniques such as electrodynamical shakers and hammer impact excitation, a plasma probe can offer distinct advantages without altering the structure's dynamics since it is contactless. Furthermore, in comparison with laser excitation, plasma excitation provides a higher power level. Additionally, while pressurized air systems are applicable for limited low frequencies, plasma probes can perform at higher frequencies. Our findings in this study suggest that CAP is comparable with acoustic excitation, indicating its potential as an effective mechanical excitation method.

Cold Atmospheric Pressure Plasma Solutions for Sustainable Food Packaging.

Increasing the number of resistant bacteria resistant to treatment is one of the leading causes of death worldwide. These bacteria are created in wounds and injuries and can be transferred through hospital equipment. Various attempts have been made to treat these bacteria in recent years, such as using different drugs and new sterilization methods. However, some bacteria resist drugs, and other traditional methods cannot destroy them. In the meantime, various studies have shown that cold atmospheric plasma can kill these bacteria through different mechanisms, making cold plasma a promising tool to deactivate bacteria. This new technology can be effectively used in the food industry because it has the potential to inactivate microorganisms such as spores and microbial toxins and increase the wettability and printability of polymers to pack fresh and dried food. It can also increase the shelf life of food without leaving any residue or chemical effluent. This paper investigates cold plasma's potential, advantages, and disadvantages in the food industry and sterilization.

Combined Application of Cold Physical Plasma and Chemotherapeutics against Chondrosarcoma Cells.

Chondrosarcoma (CS) is a rare malignant bone sarcoma that primarily affects cartilage cells in the femur and pelvis. While most subtypes exhibit slow growth with a very good prognosis, some aggressive subtypes have a poorer overall survival. CS is known for its resistance to chemotherapy and radiotherapy, leaving surgery as the sole effective therapeutic option. Cold physical plasma (CPP) has been explored in vitro as a potential therapy, demonstrating positive anti-tumor effects on CS cells. This study investigated the synergistic effects of combining CPP with cytostatics on CS cells. The chemotherapeutic agents cisplatin, doxorubicin, and vincristine were applied to two CS cell lines (CAL-78 and SW1353). After determining their IC20 and IC50, they were combined with CPP in both cell lines to assess their impact on the cell proliferation, viability, metabolism, and apoptosis. This combined approach significantly reduced the cell proliferation and viability while increasing the apoptosis signals compared to cytostatic therapy alone. The combination of CPP and chemotherapeutic drugs shows promise in targeting chemoresistant CS cells, potentially improving the prognosis for patients in clinical settings.

Efficacy of Cold Atmospheric Plasma vs. Chemotherapy in Triple-Negative Breast Cancer: A Systematic Review.

Breast cancer is a growing disease, with a high worldwide incidence and mortality rate among women. Among the various types, the treatment of triple-negative breast cancer (TNBC) remains a challenge. Considering the recent advances in cold atmospheric plasma (CAP) cancer research, our goal was to evaluate efficacy data from studies based on chemotherapy and CAP in TNBC cell lines and animal models. A search of the literature was carried out in the PubMed, Web of Science, Cochrane Library, and Embase databases. Of the 10,999 studies, there were fifty-four in vitro studies, three in vivo studies, and two in vitro and in vivo studies included. MDA-MB-231 cells were the most used. MTT, MTS, SRB, annexin-V/propidium iodide, trypan blue, and clonogenic assay were performed to assess efficacy in vitro, increasing the reliability and comprehensiveness of the data. There was found to be a decrease in cell proliferation after both chemotherapy and CAP; however, different protocol settings, including an extensive range of drug doses and CAP exposure times, were reported. For both therapies, a considerable reduction in tumor volume was observed in vivo compared with that of the untreated group. The treatment of TNBC cell lines with CAP proved successful, with apoptosis emerging as the predominant type of cellular death. This systematic review presents a comprehensive overview of the treatment landscape in chemotherapy and CAP regarding their efficacy in TNBC cell lines.

Nanosecond pulsed cold atmospheric plasma jet suppresses proliferation and migration of human glioblastoma cells via apoptosis promotion and EMT inhibition.

Glioblastoma (GBM) is one of the most aggressive and challenging cancers to treat. Despite extensive research on dozens of cancer cells, including GBM, the effect of cold atmospheric plasma (CAP) on the invasive migration of GBM cells has received limited attention, and the underlying mechanisms remain poorly understood. This study aims to investigate the potential molecular mechanism of ns-CAPJ in inhibiting the invasive migration of human GBM cells. The findings indicate that ns-CAPJ significantly reduces GBM cell invasion and migration, and induces apoptosis in GBM cells. Further mechanistic studies demonstrate a direct correlation between the suppression of the epithelial-mesenchymal transition (EMT) signaling pathway and ns-CAPJ's inhibitory effect on GBM cell invasion and migration. Additionally, combined with the N-acetyl cysteine (NAC, a ROS inhibitor) assay, we found that the ROS stimulated by the ns-CAPJ plays an important role in suppressing the EMT process. This work is expected to provide new insight into understanding the molecular mechanisms of how ns-CAPJ inhibits the proliferation and migration of human GBM cells.

Innovative cold atmospheric plasma (iCAP) decreases corneal ulcer formation and bacterial loads and improves anterior chamber health in methicillin resistant Staphylococcus aureus keratitis.

Bacterial keratitis is a vision-threatening infection of the cornea that is typically treated with antibiotics. However, antibiotics sometimes fail to eradicate the infection and do not prevent or repair the damage caused directly by the bacteria or the host immune response to the infection. Our group previously demonstrated that treatment of Pseudomonas aeruginosa keratitis in rabbits with innovative cold atmospheric plasma (iCAP) resulted in reduced edema, ulcer formation, and bacterial load. In this study, we investigated the efficacy of iCAP treatment in methicillin-resistant Staphylococcus aureus (MRSA). New Zealand white rabbits were infected intrastromally with MRSA then treated with iCAP, moxifloxacin, vancomycin, or combination of iCAP with each antibiotic to assess the safety and efficacy of iCAP treatment compared to untreated controls and antibiotics. iCAP treatment significantly reduced bacterial loads and inflammation, improved anterior chamber clarity, and prevented corneal ulceration compared to untreated controls and antibiotic treatment. Safety assessments of grimace test scores and tear production showed that iCAP was not significantly different from either antibiotic treatment in terms of distress or tear production. Combination iCAP/antibiotic treatment did not appear to provide significant added benefit over iCAP alone. Our findings suggest that the addition of iCAP may be a viable tool in reducing damage to the cornea and anterior chamber of the eye following S. aureus keratitis.

Cold Atmospheric Plasma: A Promising and Safe Therapeutic Strategy for Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease. Microbial infection, immune system dysfunction, and skin barrier defunctionalization have been regarded as the central events in AD pathogenesis. Cold atmospheric plasma (CAP) is an unbound system composed of many free electrons, ions, and neutral particles, with macroscopic time and spatial scales. Based on dielectric barrier discharge, glow discharge, corona discharge, or arch discharge, CAP is generated at normal atmospheric pressure. Its special physical properties maintain its temperature at 20°C-40°C, combining the advantages of high safety and strong ionic activity. CAP has been tentatively used in inflammatory or pruritic skin disorders such as psoriasis, pruritus, and ichthyosis. Increasing data suggest that CAP can attack the microbial structure due to its unique effects, such as heat, ultraviolet radiation, and free radicals, resulting in its inactivation. Meanwhile, CAP regulates reactive oxygen species and reactive nitrogen species in and out of the cells, thereby improving cell immunocompetence. In addition, CAP has a beneficial effect on the skin barrier function via changing the skin lipid contents and increasing the skin permeability to drugs. This review summarizes the potential effects of CAP on the major pathogenic causes of AD and discusses the safety of CAP application in dermatology in order to expand the clinical application value of CAP to AD.

Concise review of non-invasive physical plasma as a promising treatment option for radiation injuries of the skin.

Radiation injury has a complex pathophysiology and can result in long-term impediment of the dermal barrier function. Historically, its treatment has been no different to that of thermal burns and it is not always possible to prevent an unpredictable and uncontrolled extension of the radiation-induced reactions. Non-invasive physical plasma (NIPP), a highly energised gas encompassing a combination of various reactive species, positively affects the key players involved in wound healing and proves to be a promising treatment option for chronic wounds and inflammatory skin disorders. Recent clinical evidence also suggests preliminary efficacy in radiation injury following therapeutic irradiation as a part of cancer therapy. Further research is warranted to also investigate the clinical value of NIPP in the context of unplanned or accidental radiation exposure, either as a topical treatment or possibly as an intraoperative procedure, to potentially improve the dermatological outcome and reduce symptoms in radiation victims.

Recent advances in cold atmospheric plasma (CAP) for breast cancer therapy.

The serious problems of conventional breast cancer therapy strategies such as drug resistance, severe side effects, and lack of selectivity prompted the development of various cold atmospheric plasma (CAP) devices. Due to its advanced technology, CAP can produce a unique environment rich in reactive oxygen and nitrogen species (RONS), photons, charged ions, and an electric field, making it a promising revolutionary platform for cancer therapy. Despite substantial technological successes, CAP-based therapeutic systems are encounter with distinct limitations, including low control of the generated RONS, poor knowledge about its anticancer mechanisms, and challenges concerning designing, manufacturing, clinical translation, and commercialization, which must be resolved. The latest developments in CAP-based therapeutic systems for breast cancer treatment are discussed in this review. More significantly, the integration of CAP-based medicine approaches with other breast cancer therapies, including chemo- and nanotherapy is thoroughly addressed.

Bactericidal effect of low-temperature atmospheric plasma against the Shigella flexneri.

BACKGROUND: Shigella flexneri (S. flexneri) is a common intestinal pathogenic bacteria that mainly causes bacillary dysentery, especially in low socioeconomic countries. This study aimed to apply cold atmospheric plasma (CAP) on S. flexneri directly to achieve rapid, efficient and environmentally friendly sterilization. METHODS: The operating parameters of the equipment were determined by plasma diagnostics. The plate count and transmission electron microscope were employed to calculate bacterial mortality rates and observe the morphological damage of bacterial cells. Measurement of intracellular reactive oxygen species (ROS) and superoxide anions were detected by 2,7-dichlorodihydrofluorescein (DCFH) and Dihydroethidium fluorescence probes, respectively. The fluorescence intensity (a. u.) reflects the relative contents. Additionally, the experiment about the single effect of temperature, ultraviolet (UV), and ROS on bacteria was conducted. RESULTS: The peak discharge voltage and current during plasma operation were 3.92kV and 66mA. After discharge, the bacterial mortality rate of 10, 20, 30 and 40 s of plasma treatment was 60.71%, 74.02%, 88.11% and 98.76%, respectively. It was shown that the intracellular ROS content was proportional to the plasma treatment time and ROS was the major contributor to bacterial death. CONCLUSION: In summary, our results illustrated that the plasma treatment could inactivate S. flexneri efficiently, and the ROS produced by plasma is the leading cause of bacterial mortality. This highly efficient sterilization method renders plasma a highly promising solution for hospitals, clinics, and daily life.

Mechanisms of bacterial inhibition and tolerance around cold atmospheric plasma.

The grim situation of bacterial infection has undoubtedly become a major threat to human health. In the context of frequent use of antibiotics, a new bactericidal method is urgently needed to fight against drug-resistant bacteria caused by non-standard use of antibiotics. Cold atmospheric plasma (CAP) is composed of a variety of bactericidal species, which has excellent bactericidal effect on microbes. However, the mechanism of interaction between CAP and bacteria is not completely clear. In this paper, we summarize the mechanisms of bacterial killing by CAP in a systematic manner, discuss the responses of bacteria to CAP treatment that are considered to be related to tolerance and their underlying mechanisms, review the recent advances in bactericidal applications of CAP finally. This review indicates that CAP inhibition and tolerance of survival bacteria are a set of closely related mechanisms and suggests that there might be other mechanisms of tolerance to survival bacteria that had not been discovered yet. In conclusion, this review shows that CAP has complex and diverse bactericidal mechanisms, and has excellent bactericidal effect on bacteria at appropriate doses. KEY POINTS: • The bactericidal mechanism of CAP is complex and diverse. • There are few resistant bacteria but tolerant bacteria during CAP treatment. • There is excellent germicidal effect when CAP in combination with other disinfectants.

Cold atmospheric nitrogen plasma induces metal-initiated cell death by cell membrane rupture and mitochondrial perturbation.

Cold atmospheric plasma (CAP) is a novel biomedical tool used for cancer therapy. A device using nitrogen gas (N2 CAP) produced CAP that induced cell death through the production of reactive nitrogen species and an increase in intracellular calcium. In this study, we investigated the effect of N2 CAP-irradiation on cell membrane and mitochondrial function in human embryonic kidney cell line 293T. We investigated whether iron is involved in N2 CAP-induced cell death, as deferoxamine methanesulfonate (an iron chelator) inhibits this process. We found that N2 CAP induced cell membrane disturbance and loss of mitochondrial membrane potential in an irradiation time-dependent manner. BAPTA-AM, a cell-permeable calcium chelator, inhibited N2 CAP-induced loss of mitochondrial membrane potential. These results suggest that disruption of intracellular metal homeostasis was involved in N2 CAP-induced cell membrane rupture and mitochondrial dysfunction. Moreover, N2 CAP irradiation generated a time-dependent production of peroxynitrite. However, lipid-derived radicals are unrelated to N2 CAP-induced cell death. Generally, N2 CAP-induced cell death is driven by the complex interaction between metal movement and reactive oxygen and nitrogen species produced by N2 CAP.

The therapeutic perspective of cold atmospheric plasma in periodontal disease.

OBJECTIVES: Periodontal disease (PD) is one of the most common infectious diseases with complex inflammatory conditions, having irreversibly destructive impacts on the periodontal supporting tissues. The application of cold atmospheric plasma (CAP) is a promising adjuvant therapy modality for PD. However, the mechanism of CAP in PD treatment is still poorly understood. The review motivates to outline the latest researches concerning the applications of CAP in PD treatment. METHODS: We searched CAP-related literature through utilizing the well-established databases of Pubmed, Scopus and Web of Science according to the following keywords related to periodontal disease (periodontal, gingival, gingivitis, gingiva, periodontium, periodontitis). RESULTS: A total of 18 concerning original studies were found. These studies could be classified according to three pathophysiological perspectives of PD. The therapeutic mechanisms of CAP may be attributed to the oxidative stress-related cell death of periodontal bacteria, the suppression of periodontal inflammation and pro-inflammatory cytokine secretion, as well as the acceleration of periodontal soft tissue wound healing and hard tissue reconstruction. CONCLUSIONS: Cold atmospheric plasma has potential therapeutic effects on PD through three mechanisms: antimicrobial effect, inflammation attenuation, and tissue remodeling. This review hopefully provides a comprehensive perspective into the potential of CAP in PD therapy.

Transdermal cold atmospheric plasma-mediated immune checkpoint blockade therapy.

Despite the promise of immune checkpoint blockade (ICB) therapy against cancer, challenges associated with low objective response rates and severe systemic side effects still remain and limit its clinical applications. Here, we described a cold atmospheric plasma (CAP)-mediated ICB therapy integrated with microneedles (MN) for the transdermal delivery of ICB. We found that a hollow-structured MN (hMN) patch facilitates the transportation of CAP through the skin, causing tumor cell death. The release of tumor-associated antigens then promotes the maturation of dendritic cells in the tumor-draining lymph nodes, subsequently initiating T cell-mediated immune response. Anti-programmed death-ligand 1 antibody (aPDL1), an immune checkpoint inhibitor, released from the MN patch further augments the antitumor immunity. Our findings indicate that the proposed transdermal combined CAP and ICB therapy can inhibit the tumor growth of both primary tumors and distant tumors, prolonging the survival of tumor-bearing mice.