Manganese-mediated potentiation of antitumor immune responses by enhancing KLRG1+ Macrophage function.

Manganese (Mn) play a crucial role in various biological processes in the body. Studies have primarily focused on their ability to enhance immune cell function and activation against tumors, particularly in dendritic cells (DCs), macrophages, and T cells. Tumor-associated macrophages (TAMs) are often the most abundant immune cell population present in the tumor microenvironment (TME). Thus, it would be valuable to investigate the mechanism by which Mn2+ regulates TAMs' involvement in anti-tumor immunity, as it be crucial for advancing our understanding of cancer biology and developing new treatments for cancer. Here, in the present study we discovered that Mn2+ treatment led to a significant increase in KLRG1+ macrophages (KLRG1+ Mφ) in tumor tissues, and most of these cells exhibited an M1 phenotype. Knocking down KLRG1 in macrophages not only impaired their ability to induce downstream anti-tumor immunity of adaptive immune cells, but also impaired their direct cytotoxicity against tumor cells. Moreover, the changes in the polarization phenotype of KLRG1+ macrophages further lead to T cell proliferation and the polarization of CD4+ T cells towards a Th1 phenotype, thereby establishing a foundation for the antitumor immune response. Our study expands the understanding of the anti-tumor mechanism of Mn2+ and demonstrates, for the first time, that Mn2+ can regulate the function of KLRG1+ Mφ to participate in anti-tumor activities. These findings suggest that KLRG1 may represent a promising target for developing new tumor therapy.

Combination of IL-33 with PD-1 blockade augment mILC2s-mediated anti-tumor immunity.

BACKGROUND: Group 2 innate lymphoid cells (ILC2s) represent one of the main tissue-specific innate lymphoid cell populations, which are key drivers of cytokine secretion in their occupational niche. However, the precise involvement of ILC2s in cancer immunity and their potential impact on immunotherapeutic approaches remain poorly understood. METHODS: The proportion of ILC2s originating from various tissue sources were quantified through flow cytometry, along with the determination of CD4+ T cell and CD8+ T cell percentages. Flow cytometry was also employed to assess IFN-γ production and programmed cell death protein-1 (PD-1) expression in T cells. Immunohistochemistry was utilized to detect IL-33 expression in tumor tissues, while immunofluorescence was employed to confirm the infiltration of ILC2s in both murine and human tumor tissues. RESULTS: In this study, we provide evidence that intra-tumoral ILC2s in lung adenocarcinoma (LUAD) exist in a quiescent state. However, the activation of intra-tumoral ILC2s is induced by IL-33 specifically in a natural ILC2s (nILC2, ST2+KLRG1-) phenotype. Considering the pivotal role of PD-1 in cancer immunotherapy and its immunoregulatory functions, we investigated the synergistic effects of IL-33 and anti-PD-1 and found that their combination enhances anti-tumor immunity and improves the efficacy of immunotherapy. Moreover, this combination leads to the upregulation of activated mature ILC2s (mILC2, ST2+KLRG1+) phenotype, thereby highlighting the activated ILC2s as a novel enhancer of the immunoregulatory properties of anti-PD-1. CONCLUSIONS: Collectively, these findings underscore the significance of ILC2s and their contribution to the anti-tumor response in the context of cancer immunotherapy. Consequently, the simultaneous targeting of ILC2s and T cells represents a potentially promising and widely applicable strategy for immunotherapeutic interventions.

Novel prognostic signature for lung adenocarcinoma based on immune-related mRNA pairs.

Lung adenocarcinoma (LUAD) is a highly lethal malignant tumor. While the involvement of multiple mRNAs in the progression of LUAD is well established, the potential diagnostic value of immune-related mRNAs (irmRNAs) in LUAD remains largely unexplored. In this study, we utilized RNA-seq, clinical data, and immune-related gene information from LUAD patients to identify differentially expressed immune-related mRNAs (DEirmRNAs) and developed a predictive risk model based on specific DEirmRNA pairs closely linked with patient prognosis. We classified patients into high-risk and low-risk groups and analyzed factors such as survival rate, clinical characteristics, gene enrichment, immune cell infiltration, tumor mutation load, and drug susceptibility. We confirmed the expression levels of these DEirmRNAs in tumor tissues using qRT-PCR assay. Our results showed that the low-risk group had a longer survival time and lower tumor mutation burden (TMB) and microsatellite instability (MSI) compared to the high-risk group. The high-risk group also had a significant reduction in the number of certain immune cells and a lower half-maximum inhibitor concentration (IC50). We identified specific DEirmRNA pairs that were up-regulated or down-regulated in tumor tissues compared to adjacent tissues. Our prognostic risk model based on DEirmRNA pairs could be used to predict the prognosis of LUAD patients and provide reference for better treatment.

Gel-mediated recruitment of conventional type 1 dendritic cells potentiates the therapeutic effects of radiotherapy.

The efficacy of radiotherapy has not yet achieved optimal results, partially due to insufficient priming and infiltration of effector immune cells within the tumor microenvironment (TME), which often exhibits suppressive phenotypes. In particular, the infiltration of X-C motif chemokine receptor 1 (XCR1)-expressing conventional type-1 dendritic cells (cDC1s), which are critical in priming CD8+ cytotoxic T cells, within the TME is noticeably restricted. Hence, we present a facile methodology for the efficient fabrication of a calcium phosphate hydrogel loaded with X-C motif chemokine ligand 1 (XCL1) to selectively recruit cDC1s. Manganese phosphate microparticles were also loaded into this hydrogel to reprogram the TME via cGAS-STING activation, thereby facilitating the priming of cDC1s propelled specific CD8+ T cells. They also polarize tumor-associated macrophages towards the M1 phenotype and reduce the proportion of regulatory cells, effectively reversing the immunosuppressive TME into an immune-active one. The yielded XCL1@CaMnP gel exhibits significant efficacy in enhancing the therapeutic outcomes of radiotherapy, particularly when concurrently administered with postoperative radiotherapy, resulting in an impressive 60 % complete response rate. Such XCL1@CaMnP gel, which recruits cDC1s to present tumor antigens generated in situ, holds great potential as a versatile platform for enhanced cancer treatment through modulating the immunosuppressive TME.

Self-fueling ferroptosis-inducing microreactors based on pH-responsive Lipiodol Pickering emulsions enable transarterial ferro-embolization therapy.

Lipiodol chemotherapeutic emulsions remain one of the main choices for the treatment of unresectable hepatocellular carcinoma (HCC) via transarterial chemoembolization (TACE). However, the limited stability of Lipiodol chemotherapeutic emulsions would lead to rapid drug diffusion, which would reduce the therapeutic benefit and cause systemic toxicity of administrated chemotherapeutics. Therefore, the development of enhanced Lipiodol-based formulations is of great significance to enable effective and safe TACE treatment. Herein, a stable water-in-oil Lipiodol Pickering emulsion (LPE) stabilized by pH-dissociable calcium carbonate nanoparticles and hemin is prepared and utilized for efficient encapsulation of lipoxygenase (LOX). The obtained LOX-loaded CaCO3&hemin-stabilized LPE (LHCa-LPE) showing greatly improved emulsion stability could work as a pH-responsive and self-fueling microreactor to convert polyunsaturated fatty acids (PUFAs), a main component of Lipiodol, to cytotoxic lipid radicals through the cascading catalytic reaction driven by LOX and hemin, thus inducing ferroptosis of cancer cells. As a result, such LHCa-LPE upon transcatheter embolization can effectively suppress the progression of orthotopic N1S1 HCC in rats. This study highlights a concise strategy to prepare pH-responsive and stable LPE-based self-fueling microreactors, which could serve as bifunctional embolic and ferroptosis-inducing agents to enable proof-of-concept transarterial ferro-embolization therapy of HCC.

Efferocytosis Nanoinhibitors to Promote Secondary Necrosis and Potentiate the Immunogenicity of Conventional Cancer Therapies for Improved Therapeutic Benefits.

Efferocytosis of apoptotic cancer cells by tumor-associated macrophages or other phagocytes is reported to promote tumor immunosuppression by preventing them from secondary necrosis, which would lead to the release of intracellular components and thus enhanced immunogenicity. Therefore, current apoptosis-inducing cancer treatments (e.g., chemotherapy and radiotherapy) are less satisfactory in eliciting antitumor immunity. Herein, a nanoparticulate inhibitor of efferocytosis is prepared by encapsulating BMS777607, a hydrophobic inhibitor of receptors in macrophages responsible for phosphatidylserine-dependent efferocytosis, with biocompatible poly(lactic-co-glycolic acid) and its amphiphilic derivatives. The yielded nano-BMS can inhibit the efferocytosis of apoptotic cancer cells, thus redirecting them to immunogenic secondary necrosis. As a result, intratumorally injected nano-BMS is capable of activating both innate and adaptive antitumor immunity to achieve greatly improved therapeutic responses, when synergized with nonimmunogenic chemotherapy by cisplatin, immunogenic chemotherapy by oxaliplatin, or radiotherapy by external beams. Moreover, we further demonstrate that the inhalation of nano-BMS could significantly promote the efficacy of cisplatin chemotherapy to suppress tumor lung metastases. Therefore, this study highlights a general strategy to potentiate the immunogenicity of different cancer treatments by suppressing efferocytosis-propelled tumor immunosuppression, showing tremendous clinical potential in rescuing existing cancer therapies for more effective treatment.

Activation of the GPR35 on ILC2 drives immunosuppression to promote lung cancer progression.

Lung cancer is the most common cancer type with poor prognosis. While G protein-coupled receptor 35 (GPR35) is a potent stimulator of tumor growth, group 2 innate lymphoid cells (ILC2) have shown dual effects in tumorigenesis. Intriguingly, inflammation induced GPR35 activation leads to an upregulation in the markers associated with ILC2. Here, we reported that GPR35 knockout mice exhibited a significantly reduced tumor growth and altered immune infiltration in tumors. Furthermore, activating GPR35 in different mouse models promoted tumor development by enhancing the production of IL-5 and IL-13, thereby facilitating the formation of the ILC2-MDSC axis. Moreover, we found that GPR35 was a poor prognostic factor in patients with lung adenocarcinoma. Together, our findings suggest the potential application of targeting GPR35 in cancer immunotherapy.

[Imbalance of lymphoid cells in peripheral blood maintains the immunosuppression and promotes the development of lung adenocarcinoma].

Objectives Objectives To investigate how the imbalance of innate lymphoid cells (ILCs)in the peripheral blood of patients with lung adenocarcinoma affects the balance of downstream mononuclear macrophages and T helper (Th) cells, and to identify the impact of the imbalance of ILCs on the immune status and prognosis of lung adenocarcinoma. Methods The peripheral blood of 20 patients with lung adenocarcinoma and normal controls were collected. The percentage of ILCs, mononuclear macrophages and T lymphocyte in peripheral blood were analyzed by flow cytometry. The characteristic cytokine secretion levels of various types of immune cells in peripheral blood were detected by real-time fluorescence quantitative PCR. Results Compared with the normal controls, the proportion of M2 mononuclear macrophages, ILC1 and ILC2 in patients with lung adenocarcinoma was up-regulated, while the proportion of M1 mononuclear macrophages, CD4+ T and CD8+ T was down-regulated. The mRNA expression of related cytokines of M1 mononuclear macrophages and ILC1 were decreased; while the mRNA expression of related cytokines of M2 mononuclear macrophages and ILC2 were increased. Along with the decreased CD4+T cells-associated cytokine T-bet mRNA expression, and the increased GATA3 mRNA expression. Moreover, the expression of PD-1 in CD8+ T cells was also up-regulated. Conclusion The imbalance of ILCs in peripheral blood of patients with lung adenocarcinoma promotes the imbalance of mononuclear macrophages and Th cells, which altogether maintains the immunosuppression in patients with lung adenocarcinoma, and promotes the development of lung adenocarcinoma.

X-ray-Induced Release of Nitric Oxide from Hafnium-Based Nanoradiosensitizers for Enhanced Radio-Immunotherapy.

Radiotherapy (RT) is an extensively used strategy for cancer treatment, but its therapeutic effect is usually limited by the abnormal tumor microenvironment (TME) and it lacks the ability to control tumor metastases. In this work, a nanoscale coordination polymer, Hf-nIm@PEG (HNP), is prepared by the coordination of hafnium ions (Hf4+ ) with 2-nitroimidazole (2-nIm), and then modified with lipid bilayers containing poly(ethylene glycol) (PEG). Under low-dose X-ray irradiation, on the one hand, Hf4+ with high computed tomography signal enhancement ability can deposit radiation energy to induce DNA damage, and on the other hand, NO can be persistently released from 2-nIm, which can not only directly react with the radical DNA to prevent the repair of damaged DNA but also relieves the hypoxic immunosuppressive TME to sensitize radiotherapy. Additionally, NO can also react with superoxide ions to generate reactive nitrogen species (RNS) to induce cell apoptosis. More interestingly, it is discovered that Hf4+ can effectively activate the cyclic-di-GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway to promote the immune responses induced by radiotherapy. Thus, this work presents a simple but multifunctional nanoscale coordination polymer to deposit radiation energy, trigger the release of NO, modulate the TME, activate the cGAS-STING pathway, and finally realize synergistic radio-immunotherapy.

A low-fouling electrochemical biosensor for biomarker detection in serum based on designed α/ß-peptides with anti-enzymolysis and antifouling capabilities.

The zwitterionic peptides, especially those composed of glutamic (E) and lysine (K) groups have drawn enormous attention as antifouling biomaterials owing to their strong hydration capability and biocompatibility. However, the susceptibility of α-amino acid K to the proteolytic enzymes in human serum limited the broad application of such peptides in biological media. Herein, a new multifunctional peptide with favorable stability in human serum was designed, and it was composed of three sections with immobilizing, recognizing and antifouling capabilities, respectively. The antifouling section was composed of alternating E and K amino acids, but the enzymolysis-susceptive amino acid α-K was replaced by the unnatural ß-K. Compared with the conventional peptide composed of all α-amino acids, the α/ß-peptide exhibited significantly enhanced stability and longer antifouling performance in human serum and blood. The electrochemical biosensor based on the α/ß-peptide showed a favorable sensitivity to its target IgG, with a quite wide linear range from 100 pg mL-1 to 10 µg mL-1 and a low detection limit (33.7 pg mL-1, S/N = 3), and it was promising for the detection of IgG in complex human serum. The tactic of designing antifouling α/ß-peptides offered an efficient way to develop low-fouling biosensors with robust operation in complex body fluids.

Precise Epitope Organization with Self-adjuvant Framework Nucleic Acid for Efficient COVID-19 Peptide Vaccine Construction.

Peptide vaccines have advantages in easy fabrication and high safety, but their effectiveness is hampered by the poor immunogenicity of the epitopes themselves. Herein, we constructed a series of framework nucleic acids (FNAs) with regulated rigidity and size to precisely organize epitopes in order to reveal the influence of epitope spacing and carrier rigidity on the efficiency of peptide vaccines. We found that assembling epitopes on rigid tetrahedral FNAs (tFNAs) with the appropriate size could efficiently enhance their immunogenicity. Further, by integrating epitopes from SARS-CoV-2 on preferred tFNAs, we constructed a COVID-19 peptide vaccine which could induce high titers of IgG against the receptor binding domain (RBD) of SARS-CoV-2 spike protein and increase the ratio of memory B and T cells in mice. Considering the good biocompatibility of tFNAs, our research provides a new idea for developing efficient peptide vaccines against viruses and possibly other diseases.

Poly(lactic acid) based Pearl Layer Moistureproof Membrane for Flexible Laminated Packaging.

The development of bio-based polymer materials, such as polylactic acid (PLA) -based polymers, is an effective strategy to reduce dependence on petrochemical-based polymers. However, the preparation of bio-based polymers with high barrier properties is a major challenge. To overcome this challenge, a nacreous layer structure with a ' brick and mud ' pattern is mimicked to improve the overall performance of the material. In this paper, Poly (L -lactic acid) (PLLA) and Polypropylene Glycol (PPG) was combined to prepare bio-based polyurethane (PU-PLLA), which is used as the slurry structure of nacreous layer. The bio-based biomimetic composite membrane (PU-PLLA/BN) is then obtained by adding boron nitride (BN, brick structure of pearl layer) to it. The water vapor permeability test results show that the permeability of PU-PLLA material can be reduced by more than 50% by 5 wt.% BN, which is because the addition of BN can increase the length and tortuosity of the gas molecular diffusion path in the composite. Therefore, this pearl-inspired PU-PLLA/BN film has excellent moisture resistance, which opens up a broad road for the practical application of PLLA in flexible laminated packaging.

Biomaterials-assisted construction of neoantigen vaccines for personalized cancer immunotherapy.

INTRODUCTION: Cancer vaccine represents a promising strategy toward personalized immunotherapy, and its therapeutic potency highly relies on the specificity of tumor antigens. Among these extensively studied tumor antigens, neoantigens, a type of short synthetic peptides derived from random somatic mutations, have been shown to be able to elicit tumor-specific antitumor immune response for tumor suppression. However, challenges remain in the efficient and safe delivery of neoantigens to antigen-presenting cells inside lymph nodes for eliciting potent and sustained antitumor immune responses. The rapid advance of biomaterials including various nanomaterials, injectable hydrogels, and macroscopic scaffolds has been found to hold great promises to facilitate the construction of efficient cancer vaccines attributing to their high loading and controllable release capacities. AREAS COVERED: In this review, we will summarize and discuss the recent advances in the utilization of different types of biomaterials to construct neoantigen-based cancer vaccines, followed by a simple perspective on the future development of such biomaterial-assisted cancer neoantigen vaccination and personalized immunotherapy. EXPERT OPINION: These latest progresses in biomaterial-assisted cancer vaccinations have shown great promises in boosting substantially potentiated tumor-specific antitumor immunity to suppress tumor growth, thus preventing tumor metastasis and recurrence.

Tannic Acid Crosslinked Self-Healing and Reprocessable Silicone Elastomers with Improved Antibacterial and Flame Retardant Properties.

Silicone elastomers are widely used in aviation, electronics, automotive, and medical device fields, and their overuse inevitably causes recycled problems. In addition, the elastomers are subject to attack by bacteria and fire during use in some application scenarios, which is a safety hazard. Therefore, there is a great need to prepare silicone elastomers with improved antibacterial, flame retardant, self-healing, and recyclable functions. A new strategy is proposed to prepare silicone elastomers with bio-based tannic acid as cross-linkers to solve this problem by using polydimethylsiloxane as a soft chain segment and 2,2-bis(hydroxymethyl)propionic acid as an intermediate chain extender. Based on the phenol carbamate bonding and hydrogen bonding interactions, the elastomer has efficient self-healing ability and can achieve dynamic dissociation at 120 °C for complete recovery. In addition, due to the unique spatial structure and polyphenolic hydroxyl groups of tannic acid, the mechanical properties of the elastomer are greatly improved with an antimicrobial efficiency of over 90% and a final oxygen index of 25.5%. The multifunctional silicone elastomer has great potential applications in recyclable refractory materials and antimicrobial materials.

Serum sPD1 and sPDL1 as Biomarkers for Evaluating the Immune State of Lung Adenocarcinoma Patients.

A large proportion of cancer patients benefit from immune checkpoint therapy, while few studies focused on the relationship between soluble PD1 (sPD1) and soluble PDL1 (sPDL1) in serum and immune status of patients. ILC2 and M2 were confirmed to be related to immunosuppression in tumor patients. To determine whether sPD1 and sPDL1 are correlated with the ratio of ILC2 and M2 is helpful to explore the possibility of using sPD1 and sPDL1 as tumor molecular markers. Our results showed an immune balance toward ILC2 and M2-like monocytes in patients with LUAD compared with healthy controls. Meanwhile, decreased CD4+T and CD8+T cells, as well as elevated PD1+CD8+T cells, were found in patients with LUAD. The relative mRNA expression levels of ILC2- and M2-characteristic cytokines were also upregulated accompanied by decreased mRNA expression levels of ILC1- and M1-characteristic cytokines in patients with LUAD compared to healthy controls. Moreover, elevated ILC2 frequencies as well as the amount of IL-13 were positively correlated with the amount of sPD1, however, there was no correlation between them and sPDL1. These results suggested that sPD1 and sPDL1 can serve as diagnostic markers to predict the immune state of cancer patients.

Chemical Modulation of Glucose Metabolism with a Fluorinated CaCO3 Nanoregulator Can Potentiate Radiotherapy by Programming Antitumor Immunity.

Tumor hypoxia and acidity are well-known features in solid tumors that cause immunosuppression and therapeutic resistance. Herein, we rationally synthesized a multifunctional fluorinated calcium carbonate (fCaCO3) nanoregulator by coating CaCO3 nanoparticles with dopamine-grafted perfluorosebacic acid (DA2-PFSEA) and ferric ions by utilizing their coordination interaction. After PEGylation, the obtained fCaCO3-PEG showed high loading efficacy to perfluoro-15-crown-5-ether (PFCE), a type of perfluorocarbon with high oxygen solubility, thereby working as both oxygen nanoshuttles and proton sponges to reverse tumor hypoxia and acidity-induced resistance to radiotherapy. The as-prepared PFCE@fCaCO3-PEG could not only function as long-circulating oxygen nanoshuttles to attenuate tumor hypoxia but also neutralize the acidic tumor microenvironment by restricting the production of lactic acid and reacting with extracellular protons. As a result, treatment with PFCE@fCaCO3-PEG could improve the therapeutic outcome of radiotherapy toward two murine tumors with distinct immunogenicity. The PFCE@fCaCO3-PEG-assisted radiotherapy could also collectively inhibit the growth of unirradiated tumors and reject rechallenged tumors by synergistically eliciting protective antitumor immunity. Therefore, our work presents the preparation of fluorinated CaCO3 nanoregulators to reverse tumor immunosuppression and potentiate radiotherapy through chemically modulating tumor hypoxic and acidic microenvironments tightly associated with tumor glucose metabolism.

d-Amino Acid-Based Antifouling Peptides for the Construction of Electrochemical Biosensors Capable of Assaying Proteins in Serum with Enhanced Stability.

The susceptibility of peptides to proteolytic degradation in human serum significantly hindered the potential application of peptide-based antifouling biosensors for long-term assaying of clinical samples. Herein, a robust antifouling biosensor with enhanced stability was constructed based on peptides composed of d-amino acids (d-peptide) with prominent proteolytic resistance. The electrode was electropolymerized with poly(3,4-ehtylenedioxythiophene) and electrodeposited with Au nanoparticles (AuNPs), and the d-peptide was then immobilized onto the AuNPs, and a typical antibody specific for immunoglobulin M (IgM) was immobilized. Because of the effect of d-amino acids, the d-peptide-modified electrode surface showed prominent antifouling capability and high tolerance to enzymatic hydrolysis. Moreover, the d-peptide-modified electrode exhibited much stronger long-term stability, as well as antifouling ability in human serum than the electrode modified with normal peptides. The electrochemical biosensor exhibited a sensitive response to IgM linearly within the range of 100 pg mL-1 to 1.0 µg mL-1 and a very low detection limit down to 37 pg mL-1, and it was able to detect IgM in human serum with good accuracy. This work provided a new strategy to develop robust peptide-based biosensors to resist the proteolytic degradation for practical application in complex clinical samples.

Engineering bioluminescent bacteria to boost photodynamic therapy and systemic anti-tumor immunity for synergistic cancer treatment.

The limited penetration depth of external excitation light would remarkably impair the therapeutic efficacy of photodynamic therapy (PDT) and its clinical utilization. Herein, we engineered bioluminescent bacteria by transforming attenuated Salmonella typhimurium strain ΔppGpp (S.T.ΔppGpp) with firefly-luciferase-expressing plasmid (Luc-S.T.ΔppGpp) as an internal light source to evenly illuminate whole tumors. Upon being fixed inside tumors with in-situ formed hydrogel, the colonized Luc-S.T.ΔppGpp together with D-luciferin could continuously generate light to excite photosensitizer chlorin e6 (Ce6), leading to effective suppression of different types of tumors including opaque melanoma and large rabbit tumors. Such bioluminescence-triggered PDT presented significant advantages over conventional PDT excited with an external 660-nm light, which at a much high light energy could only slightly retard the growth of small subcutaneous tumors. Furthermore, we uncovered that Luc-S.T.ΔppGpp boosted PDT could also elicit potent antitumor immunity post the treatment to inhibit tumor metastasis and prevent tumor challenge. Therefore, this work highlights that such bioluminescent bacteria boosted PDT is a general and highly effective therapeutic approach toward diverse cancers with varying light-absorbing capacities and tumor sizes, promising for potential clinical translation because of their acceptable safety profiles.

An electrochemical biosensor for alpha-fetoprotein detection in human serum based on peptides containing isomer D-Amino acids with enhanced stability and antifouling property.

The development of antifouling biosensors capable of detecting biomarkers at low concentrations in complex bio-fluids with many interference components is of great importance in the diagnosis and treatment of diseases. Certain zwitterionic peptides composed of natural L-amino acids have been used for the construction of low fouling biosensors and demonstrated excellent antifouling performances, but they are prone to enzymatic degradation in biological media, such as serum that contains a variety of enzymes. In this work, a novel antifouling peptide with the sequence of cppPPEKEKEkek was designed, and three unnatural D-amino acids were set at both ends of the peptide to enhance its tolerance to enzymatic degradation. An electrochemical biosensor was constructed by coupling the antifouling peptide with a conducting polymer polyaniline (PANI) to achieve accurate detection of alpha-fetoprotein (AFP) in clinical samples. Owing to the presence of the designed peptide with partial D-amino acids (pD-peptide), the biosensing interface showed significantly high antifouling performance and enhanced stability in human serum. Meanwhile, the pD-peptide based biosensor exhibited high sensitivity toward the target AFP, with the linear range from 0.1 fg mL-1 to 1.0 ng mL-1 and the limit of detection of 0.03 fg mL-1 (S/N = 3). This strategy of enhancing the stability (tolerance to enzymolysis) of antifouling peptides in biological samples provided an effective way to develop antifouling biosensors for practical applications.

Direct and indirect anticancer effects of hyperthermic intraperitoneal chemotherapy on peritoneal malignancies (Review).

The successful application of hyperthermic intraperitoneal chemotherapy (HIPEC) illustrates its antitumor activity against primary malignances and peritoneal metastases. Although the specific underlying molecular mechanisms remain unclear, increasing evidence suggest that HIPEC directly and indirectly inhibits tumor growth, and prolongs overall survival in both hyperthermic and chemotherapeutic manners. To demonstrate the superiority and limitations of such a therapeutic regimen, the present review focuses on the biological and immunological anticancer mechanisms of HIPEC. In addition, the potential combination of HIPEC with other therapies is discussed, as well as its potential to prolong the overall survival time of patients with peritoneal malignancies.