Plasmodium vivax serological exposure markers: PvMSP1-42-induced humoral and memory B-cell response generates long-lived antibodies.

Plasmodium vivax serological exposure markers (SEMs) have emerged as promising tools for the actionable surveillance and implementation of targeted interventions to accelerate malaria elimination. To determine the dynamic profiles of SEMs in current and past P. vivax infections, we screened and selected 11 P. vivax proteins from 210 putative proteins using protein arrays, with a set of serum samples obtained from patients with acute P. vivax and documented past P. vivax infections. Then we used a murine protein immune model to initially investigate the humoral and memory B cell response involved in the generation of long-lived antibodies. We show that of the 11 proteins, especially C-terminal 42-kDa region of P. vivax merozoite surface protein 1 (PvMSP1-42) induced longer-lasting long-lived antibodies, as these antibodies were detected in individuals infected with P. vivax in the 1960-1970s who were not re-infected until 2012. In addition, we provide a potential mechanism for the maintenance of long-lived antibodies after the induction of PvMSP1-42. The results indicate that PvMSP1-42 induces more CD73+CD80+ memory B cells (MBCs) compared to P. vivax GPI-anchored micronemal antigen (PvGAMA), allowing IgG anti-PvMSP1-42 antibodies to be maintained for a long time.

Research progress of 3D printed poly (ether ether ketone) in the reconstruction of craniomaxillofacial bone defects.

The clinical challenge of bone defects in the craniomaxillofacial region, which can lead to significant physiological dysfunction and psychological distress, persists due to the complex and unique anatomy of craniomaxillofacial bones. These critical-sized defects require the use of bone grafts or substitutes for effective reconstruction. However, current biomaterials and methods have specific limitations in meeting the clinical demands for structural reinforcement, mechanical support, exceptional biological performance, and aesthetically pleasing reconstruction of the facial structure. These drawbacks have led to a growing need for novel materials and technologies. The growing development of 3D printing can offer significant advantages to address these issues, as demonstrated by the fabrication of patient-specific bioactive constructs with controlled structural design for complex bone defects in medical applications using this technology. Poly (ether ether ketone) (PEEK), among a number of materials used, is gaining recognition as a feasible substitute for a customized structure that closely resembles natural bone. It has proven to be an excellent, conformable, and 3D-printable material with the potential to replace traditional autografts and titanium implants. However, its biological inertness poses certain limitations. Therefore, this review summarizes the distinctive features of craniomaxillofacial bones and current methods for bone reconstruction, and then focuses on the increasingly applied 3D printed PEEK constructs in this field and an update on the advanced modifications for improved mechanical properties, biological performance, and antibacterial capacity. Exploring the potential of 3D printed PEEK is expected to lead to more cost-effective, biocompatible, and personalized treatment of craniomaxillofacial bone defects in clinical applications.

Elicitation of T-cell-derived IFN-γ-dependent immunity by highly conserved Plasmodium ovale curtisi Duffy binding protein domain region II (PocDBP-RII).

BACKGROUND: Infections with Plasmodium ovale are widely distributed but rarely investigated, and the resulting burden of disease has been underestimated. Plasmodium ovale curtisi Duffy binding protein domain region II (PocDBP-RII) is an essential ligand for reticulocyte recognition and host cell invasion by P. ovale curtisi. However, the genomic variation, antigenicity and immunogenicity of PocDBP-RII remain major knowledge gaps. METHODS: A total of 93 P. ovale curtisi samples were collected from migrant workers who returned to China from 17 countries in Africa between 2012 and 2016. The genetic polymorphism, natural selection and copy number variation (CNV) were investigated by sequencing and real-time PCR. The antigenicity and immunogenicity of the recombinant PocDBP-RII (rPocDBP-RII) protein were further examined, and the humoral and cellular responses of immunized mice were assessed using protein microarrays and flow cytometry. RESULTS: Efficiently expressed and purified rPocDBP-RII (39 kDa) was successfully used as an antigen for immunization in mice. The haplotype diversity (Hd) of PocDBP-RII gene was 0.105, and the nucleotide diversity index (π) was 0.00011. No increased copy number was found among the collected isolates of P. ovale curtisi. Furthermore, rPocDBP-RII induced persistent antigen-specific antibody production with a serum IgG antibody titer of 1: 16,000. IFN-γ-producing T cells, rather than IL-10-producing cells, were activated in response to the stimulation of rPocDBP-RII. Compared to PBS-immunized mice (negative control), there was a higher percentage of CD4+CD44highCD62L- T cells (effector memory T cells) and CD8+CD44highCD62L+ T cells (central memory T cells) in rPocDBP-RII­immunized mice. CONCLUSIONS: PocDBP-RII sequences were highly conserved in clinical isolates of P. ovale curtisi. rPocDBP-RII protein could mediate protective blood-stage immunity through IFN-γ-producing CD4+ and CD8+ T cells and memory T cells, in addition to inducing specific antibodies. Our results suggested that rPocDBP-RII protein has potential as a vaccine candidate to provide assessment and guidance for malaria control and elimination activities.

Activated macrophage membrane-coated nanoparticles relieve osteoarthritis-induced synovitis and joint damage.

Osteoarthritis (OA) is a common joint condition that is a leading cause of disability worldwide. There are currently no disease-modifying treatments for osteoarthritis, which is associated with multiple kinds of inflammatory cytokines produced by M1 macrophages in the synovium of the joint. Despite recent therapeutic advancements with anti-cytokine biologics, the OA therapy response rate continues to be inadequate. To treat OA, the pro-inflammatory and anti-inflammatory responses of synoviocytes and macrophages must be controlled simultaneously. Therefore, the immune regulation capabilities of an ideal nano-drug should not only minimize pro-inflammatory responses but also effectively boost anti-inflammatory responses. In this paper, an M2H@RPK nanotherapeutic system was developed, KAFAK and shRNA-LEPR were condensed with polyethylenimine (PEI) to form a complex, which was then modified with hyaluronic acid (HA) to negatively charge to cover the M2 membrane. It was discovered that the repolarization of macrophages from the M1 to the M2 phenotype lowered pro-inflammatory responses while enhancing anti-inflammatory responses in macrophages and synoviocytes. In vitro and in vivo studies demonstrate that M2H@RPK dramatically decreases proinflammatory cytokines, controls synovial inflammation, and provides significant therapeutic efficacy by reducing joint damage. Overall, it has been demonstrated that M2H@RPK provides inflammation-targeted therapy by macrophage repolarization, and it represents a promising OA therapeutic strategy.

RGD peptide modified platinum nanozyme Co-loaded glutathione-responsive prodrug nanoparticles for enhanced chemo-photodynamic bladder cancer therapy.

Bladder cancer is one of the most common malignant tumors in the urinary system worldwide. The poor permeability and uncontrollable release of drug and hypoxia of tumor tissues were the main reasons leading to poor therapeutic effect of chemo-photodynamic therapy for bladder cancer. To solve the above problems, a tumor-targeting peptide Arg-Gly-Asp (RGD) modified platinum nanozyme (PtNP) co-loaded glutathione (GSH)-responsive prodrug nanoparticles (PTX-SS-HPPH/Pt@RGD-NP) was constructed. Firstly, a GSH-responsive prodrug (PTX-SS-HPPH) was prepared by introducing a disulfide bond between paclitaxel (PTX) and photosensitizer 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH), which could realize the GSH-responsive release of the drug at the tumor sites. Also, the distearoylphosphoethanolamine-poly (ethylene glycol)-RGD peptide (DSPE-PEG-RGD) modified the prodrug to enhance the targeting and permeability ability to bladder cancer cells. Besides, to alleviate the hypoxia of tumor tissues, PtNP was introduced to produce oxygen (O2) and improve photodynamic therapy efficiency. The results showed that the PTX-SS-HPPH/Pt@RGD-NP could achieve GSH-responsive drug release in tumor microenvironment, enhance the drug accumulation time and permeability at tumor sites in T24 subcutaneous tumor model and T24 orthotopic bladder tumor model, and alleviate hypoxia in tumor tissues, thus realizing enhanced chemo-photodynamic therapy for bladder cancer, and providing new strategies and methods for clinical treatment of bladder cancer.

Gold Nanorods and Polymer Micelles Mediated Dual TLR Stimulators Delivery System CPG@Au NRs/M-R848 Regulate Macrophages Reprogramming and DC Maturation for Enhanced Photothermal Immunotherapy of Melanoma.

Synergistic photothermal immunotherapy has emerged as a favorable therapeutic approach to fight cancer. However, design of an effective photothermal immunotherapy system to suppress tumor growth and simultaneously inhibit tumor metastases continues to be a challenge. Here a dual toll-like receptor agonists delivery system CPG@Au NRs/m-R848 for combined photothermal immunotherapy of melanoma is developed. CPG@Au NRs/m-R848 displays strong antitumor effects by promoting maturation of dendritic cells (DCs) and reprogramming of M2 macrophages into M1 phenotype. Moreover, immunogenic cell death (ICD) induced by photothermal ablation of Au NRs could synergistically produce in situ vaccination effect with CPG ODN and R848, generating systemic and lasting antitumor immunity. It is further proved that CPG@Au NRs/m-R848 treatment inhibits tumor growth in bilateral B16F10 tumors model by eliciting CD8+ T cell response. Overall, this work suggests that this strategy hold great potential in tumor immunotherapy by regulating tumor-associated macrophage polarization, triggering DCs maturation and inducing ICD.

Global Downregulation of Penicillin Resistance and Biofilm Formation by MRSA Is Associated with the Interaction between Kaempferol Rhamnosides and Quercetin.

The rapid development of methicillin-resistant Staphylococcus aureus (MRSA) drug resistance and the formation of biofilms seriously challenge the clinical application of classic antibiotics. Extracts of the traditional herb Chenopodium ambrosioides L. were found to have strong antibiofilm activity against MRSA, but their mechanism of action remains poorly understood. This study was designed to investigate the antibacterial and antibiofilm activities against MRSA of flavonoids identified from C. ambrosioides L. in combination with classic antibiotics, including ceftazidime, erythromycin, levofloxacin, penicillin G, and vancomycin. Liquid chromatography-mass spectrometry (LC-MS) was used to analyze the nonvolatile chemical compositions. Reverse transcription (RT)-PCR was used to investigate potential multitargets of flavonoids based on global transcriptional responses of virulence and antibiotic resistance. A synergistic antibacterial and biofilm-inhibiting activity of the alcoholic extract of the ear of C. ambrosioides L. in combination with penicillin G was observed against MRSA, which proved to be closely related to the interaction of the main components of kaempferol rhamnosides with quercetin. In regard to the mechanism, the increased sensitivity of MRSA to penicillin G was shown to be related to the downregulation of penicillinase with SarA as a potential drug target, while the antibiofilm activity was mainly related to downregulation of various virulence factors involved in the initial and mature stages of biofilm development, with SarA and/or σB as drug targets. This study provides a theoretical basis for further exploration of the medicinal activity of kaempferol rhamnosides and quercetin and their application in combination with penicillin G against MRSA biofilm infection. IMPORTANCE In this study, the synergistic antibacterial and antibiofilm effects of the traditional herb C. ambrosioides L. and the classic antibiotic penicillin G on MRSA provide a potential strategy to deal with the rapid development of MRSA antibiotic resistance. This study also provides a theoretical basis for further optimizing the combined effect of kaempferol rhamnosides, quercetin, and penicillin G and exploring anti-MRSA biofilm infection research with SarA and σB as drug targets.

Prevalence of pvmrp1 Polymorphisms and Its Contribution to Antimalarial Response.

As more sporadic cases of chloroquine resistance occur (CQR) in Plasmodium vivax (P. vivax) malaria, molecular markers have become an important tool to monitor the introduction and spread of drug resistance. P. vivax multidrug resistance-associated protein 1 (PvMRP1), as one of the members of the ATP-binding cassette (ABC) transporters, may modulate this phenotype. In this study, we investigated the gene mutations and copy number variations (CNVs) in the pvmrp1 in 102 P. vivax isolates from China, the Republic of Korea (ROK), Myanmar, Papua New Guinea (PNG), Pakistan, the Democratic People's Republic of Korea (PRK), and Cambodia. And we also obtained 72 available global pvmrp1 sequences deposited in the PlasmoDB database to investigate the genetic diversity, haplotype diversity, natural selection, and population structure of pvmrp1. In total, 29 single nucleotide polymorphisms reflected in 23 non-synonymous, five synonymous mutations and one gene deletion were identified, and CNVs were found in 2.9% of the isolates. Combined with the antimalarial drug susceptibility observed in the previous in vitro assays, except the prevalence of S354N between the two CQ sensitivity categories revealed a significant difference, no genetic mutations or CNVs associated with drug sensitivity were found. The genetic polymorphism analysis of 166 isolates worldwide found that the overall nucleotide diversity (π) of pvmrp1 was 0.0011, with 46 haplotypes identified (Hd = 0.9290). The ratio of non-synonymous to synonymous mutations (dn/ds = 0.5536) and the neutrality tests statistic Fu and Li's D* test (Fu and Li's D* = −3.9871, p < 0.02) suggests that pvmrp1 had evolved under a purifying selection. Due to geographical differences, genetic differentiation levels of pvmrp1 in different regions were different to some extent. Overall, this study provides a new idea for finding CQR molecular monitoring of P. vivax and provides more sequences of pvmrp1 in Asia for subsequent research. However, further validation is still needed through laboratory and epidemiological field studies of P. vivax samples from more regions.

Fluorescent Nitrogen-Doped Carbon Dots for Label Live Elder Blood-Stage Plasmodium falciparum through New Permeability Pathways.

To verify the size and emergence time of new permeability pathways (NPPs) in malaria parasites, the permeability of the Plasmodium falciparum-infected erythrocytes was tested with different particle sizes of nanomaterials by flow cytometry assay. The results confirmed the permeability of the host cell membrane increases with parasite maturation for the stage-development evolution of NPPs, and especially found that a particle size of about 50 nm had higher efficiency. As a kind of the novel nanomaterials, nitrogen-doped carbon dots (NCDs) showed no toxicity, specificity binding ability to the malaria parasites, and could label live elder blood-stage P. falciparum through NPPs, indicating the potential application in cell imaging. NPPs and some nanomaterials such as NCDs deserve more attention and exploration for the elimination and prevention of malaria.

Tumor-targeted/reduction-triggered composite multifunctional nanoparticles for breast cancer chemo-photothermal combinational therapy.

Breast cancer has become the most commonly diagnosed cancer type in the world. A combination of chemotherapy and photothermal therapy (PTT) has emerged as a promising strategy for breast cancer therapy. However, the intricacy of precise delivery and the ability to initiate drug release in specific tumor sites remains a challenging puzzle. Therefore, to ensure that the therapeutic agents are synchronously delivered to the tumor site for their synergistic effect, a multifunctional nanoparticle system (PCRHNs) is developed, which is grafted onto the prussian blue nanoparticles (PB NPs) by reduction-responsive camptothecin (CPT) prodrug copolymer, and then modified with tumor-targeting peptide cyclo(Asp-d-Phe-Lys-Arg-Gly) (cRGD) and hyaluronic acid (HA). PCRHNs exhibited nano-sized structure with good monodispersity, high load efficiency of CPT, triggered CPT release in response to reduction environment, and excellent photothermal conversion under laser irradiation. Furthermore, PCRHNs can act as a photoacoustic imaging contrast agent-guided PTT. In vivo studies indicate that PCRHNs exhibited excellent biocompatibility, prolonged blood circulation, enhanced tumor accumulation, allow tumor-specific chemo-photothermal therapy to achieve synergistic antitumor effects with reduced systemic toxicity. Moreover, hyperthermia-induced upregulation of heat shock protein 70 in the tumor cells could be inhibited by CPT. Collectively, PCRHNs may be a promising therapeutic way for breast cancer therapy.

Macrophage Membrane-Camouflaged shRNA and Doxorubicin: A pH-Dependent Release System for Melanoma Chemo-Immunotherapy.

Improving the efficacy of melanoma treatment remains an important global challenge. Here, we combined chemotherapy with protein tyrosine phosphatase nonreceptor type 2(Ptpn2) based immunotherapy in an effort to address this challenge. Short-hairpin RNA (shRNA) targeting Ptpn2 was coencapsulated with doxorubicin (DOX) in the cell membrane of M1 macrophages (M1HD@RPR). The prepared nanoparticles (NPs) were effectively phagocytosed by B16F10 cells and M1 macrophages, but not by M0 macrophages. Hence, NP evasion from the reticuloendothelial system (RES) was improved and NP enrichment in tumor sites increased. M1HD@RPR can directly kill tumor cells and stimulate immunogenic cell death (ICD) by DOX and downregulate Ptpn2. It can promote M1 macrophage polarization and dendritic cell maturation and increase the proportion of CD8+ T cells. M1HD@RPR killed and inhibited the growth of primary melanoma and lung metastatic tumor cells without harming the surrounding tissue. These findings establish M1HD@RPR as a safe multifunctional nanoparticle capable of effectively combining chemotherapy and gene immunotherapies against melanoma.

Role of Efflux Pump-Mediated Antibiotic Resistance in Quorum Sensing-Regulated Biofilm Formation by Salmonella Typhimurium.

This study was designed to assess the influence of efflux pump activity on the biofilm formation in Salmonella Typhimurium. Salmonella enterica subsp. enterica serovar Typhimurium ATCC 19585 (STWT) and clinically isolated S. Typhimurium CCARM 8009 (STCI) were treated with ceftriaxone (CEF), chloramphenicol (CHL), ciprofloxacin (CIP), erythromycin (ERY), norfloxacin (NOR), and tetracycline (TET) in autoinducer-containing media in the absence and presence of phenylalanine-arginine ß-naphthylamide (PAßN) to compare efflux pump activity with biofilm-forming ability. The susceptibilities of STWT and STCI were increased in the presence of PAßN. ERY+PAßN showed the highest decrease in the minimum inhibitory concentration (MIC) of ERY from 256 to 2 µg/mL against STWT and STCI. The antimicrobial activity of NOR against planktonic cells was significantly increased in the presence of PAßN, showing the lowest numbers of STWT (3.2 log CFU/cm2), and the TET+PAßN effectively inhibited the growth of STCI (5.2 log CFU/cm2). The lowest biofilm-forming abilities were observed at NOR+PAßN against STWT (biofilm-forming index, BFI < 0.41) and CEF+PAßN against STCI (BFI = 0.32). The bacteria swimming motility and relative fitness varied depending on the antibiotic and PAßN treatments. The motility diameters of STWT were significantly decreased by NOR+PAßN (6 mm) and TET+PAßN (15 mm), while the lowest motility of STCI was observed at CIP+PAßN (8 mm). The significant decrease in the relative fitness levels of STWT and STCI was observed at CIP+PAßN and NOR+PAßN. The PAßN as an efflux pump inhibitor (EPI) can improve the antimicrobial and anti-biofilm efficacy of antibiotics against S. Typhimurium. This study provides useful information for understanding the role of efflux pump activity in quorum sensing-regulated biofilm formation and also emphasizes the necessity of the discovery of novel EPIs for controlling biofilm formation by antibiotic-resistant pathogens.

Synergistic Inhibitory Effect of Polymyxin B in Combination with Ceftazidime against Robust Biofilm Formed by Acinetobacter baumannii with Genetic Deficiency in AbaI/AbaR Quorum Sensing.

Carbapenem resistance of Acinetobacter baumannii poses challenges to public health. Biofilm contributes to the persistence of A. baumannii cells. This study was designed to investigate the genetic relationships among carbapenem resistance, polymyxin resistance, multidrug resistance, biofilm formation, and surface-associated motility and evaluate the antibiofilm effect of polymyxin in combination with other antibiotics. A total of 103 clinical A. baumannii strains were used to determine antibiotic susceptibility, biofilm formation capacity, and motility. Enterobacterial repetitive intergenic consensus (ERIC)-PCR fingerprinting was used to determine the genetic variation among strains. The distribution of 17 genes related to the resistance-nodulation-cell division (RND)-type efflux, autoinducer-receptor (AbaI/AbaR) quorum sensing, oxacillinases (OXA)-23, and insertion sequence of ISAba1 element was investigated. The representative strains were chosen to evaluate the gene transcription and the antibiofilm activity by polymyxin B (PB) in combination with merapenem, levofloxacin, and ceftazidime, respectively. ERIC-PCR-dependent fingerprints were found to be associated with carbapenem resistance and multidrug resistance. The presence of blaOXA-23 was found to correlate with genes involved in ISAba1 insertion, AbaI/AbaR quorum sensing, and AdeABC efflux. Carbapenem resistance was observed to be negatively correlated with biofilm formation and positively correlated with motility. PB in combination with ceftazidime displayed a synergistic antibiofilm effect against robust biofilm formed by an A. baumannii strain with deficiency in AbaI/AbaR quorum sensing. Our results not only clarify the genetic correlation among carbapenem resistance, biofilm formation, and pathogenicity in a certain level but also provide a theoretical basis for clinical applications of polymyxin-based combination of antibiotics in antibiofilm therapy. IMPORTANCE Deeper explorations of molecular correlation among antibiotic resistance, biofilm formation, and pathogenicity could provide novel insights that would facilitate the development of therapeutics and prevention against A. baumannii biofilm-related infections. The major finding that polymyxin B in combination with ceftazidime displayed a synergistic antibiofilm effect against robust biofilm formed by an A. baumannii strain with genetic deficiency in AbaI/AbaR quorum sensing further provides a theoretical basis for clinical applications of antibiotics in combination with quorum quenching in antibiofilm therapy.

Candida Isolates From Blood and Other Normally Sterile Foci From ICU Patients: Determination of Epidemiology, Antifungal Susceptibility Profile and Evaluation of Associated Risk Factors.

Background: The clinical diagnosis and therapy for ICU patients with invasive candidiasis are challenged by the changes of Candida community composition and antimicrobial resistance. The epidemiology and drug sensitivity of candidiasis in ICU as well as its risk factors and drug resistance mechanism were investigated. Methods: In the present study, 115 patients in ICU were recruited from June 2019 through July 2020. Among them, 83 Candida isolates were identified with MALDI-TOF mass spectrometry. The susceptibility to antifungals was measured by microdilution method. The molecular mechanisms of azole-resistant Candida tropicalis were explored by sequencing, and their outcomes were explicitly documented. Results:Candida glabrata and C. tropicalis were the predominant non-C. albicans Candida. The specimen sources were mainly urine, bronchoalveolar lavage fluid and blood. The age, length of hospitalization, tracheotomy, diabetes and concomitant bacterial infection were the main risk factors for candidiasis. The majority of Candida species exhibited susceptibility to antifungals. However, certain C. tropicalis were frequently resistant to azoles. The polymorphism of the ERG11 in C. tropicalis was likely associated with azole resistance. Conclusion: The multiple risk factors for candidiasis in ICU patients need to be considered. Certain C. tropicalis exhibit resistance to azoles likely due to the ERG11 gene polymorphism.

Erratum to "Near-infrared responsive 5-fluorouracil and indocyanine green loaded MPEG-PCL nanoparticle integrated with dissolvable microneedle for skin cancer therapy" [Bioact. Mater. 5 (2020) 542-552].

[This corrects the article DOI: 10.1016/j.bioactmat.2020.04.002.].

The construction of a lymphoma cell-based, DC-targeted vaccine, and its application in lymphoma prevention and cure.

In recent years, Non-Hodgkin lymphoma (NHL) has been one of the most fast-growing malignant tumor diseases. NHL poses severe damages to physical health and a heavy burden to patients. Traditional therapies (chemotherapy or radiotherapy) bring some benefit to patients, but have severe adverse effects and do not prevent relapse. The relevance of emerging immunotherapy options (immune-checkpoint blockers or adoptive cellular methods) for NHL remains uncertain, and more intensive evaluations are needed. In this work, inspired by the idea of vaccination to promote an immune response to destroy tumors, we used a biomaterial-based strategy to improve a tumor cell-based vaccine and constructed a novel vaccine named Man-EG7/CH@CpG with antitumor properties. In this vaccine, natural tumor cells are used as a vector to load CpG-ODN, and following lethal irradiation, the formulations were decorated with mannose. The study of the characterization of the double-improved vaccine evidenced the enhanced ability of DCs targeting and improved immunocompetence, which displayed an antitumor function. In the lymphoma prevention model, the Man-EG7/CH@CpG vaccine restrained tumor formation with high efficiency. Furthermore, unlike the non-improved vaccine, the double-improved vaccine elicited an enhanced antitumor effect in the lymphoma treatment model. Next, to improve the moderate therapeutic effect of the mono-treatment method, we incorporated a chemotherapeutic drug (doxorubicin, DOX) into the process of vaccination and devised a combination regimen. Fortunately, a tumor inhibition rate of ~85% was achieved via the combination therapy, which could not be achieved by mono-chemotherapy or mono-immunotherapy. In summary, the strategy presented here may provide a novel direction in the establishment of a tumor vaccine and is the basis for a prioritization scheme of immuno-chemotherapy in enhancing the therapeutic effect on NHL.

Differentiation of white architectural paints by microscopic laser Raman spectroscopy and chemometrics.

A feasible, effective and non-destructive method that could be used to differentiate architectural paints was proposed by Microscopic laser Raman spectroscopy and chemometrics. A total of 252 white architectural paints from 7 different manufacturers were prepared for evaluating the potential of differentiating them. 5th Newton interpolation polynomial combined with Savitzky-Golay 7-point and 1st or 2nd polynomial smoothing under the 1st-order derivative were considered as the optimal pre-processing method for MLRM data. The Bayes discriminant analysis model realized 100% accuracy based on discriminant functions Z1, Z2 and Z3, which was the more useful and practical method for differentiating white architectural paints than that of multilayer perceptron and radial basis function neural network models. All samples were differentiated exactly, which was rapid and non-destructive. The designed method demonstrated the potential of Microscopic Laser Raman spectroscopy in combination with pre-processing and chemometrics as a universal, confirmatory, and accurate method for the white architectural paint differentiation in forensic science.

Ag2S nanoparticle-mediated multiple ablations reinvigorates the immune response for enhanced cancer photo-immunotherapy.

Photothermal therapy (PTT) has been widely used in cancer treatment in recent years. However, it is difficult to completely eliminate tumors by single PTT, and the effects of single dose of PTT frequency on the therapeutic outcome of PTT and the multiple PTT-induced immune response in cancer therapy also remain unclear. Here, water-soluble Ag2S nanoparticles (NPs) with optimal particle size (~15 nm) were synthesized and used as the PTT agents. The in vitro and in vivo results demonstrated that Ag2S NPs had good photothermal conversion in response to the irradiation of an 808 nm laser, and the results indicated that the NPs have potential as contrast agents for photoacoustic imaging as well as good biocompatibility. The in vivo results further revealed that the frequency of the Ag2S NP-mediated PTT affected the cancer therapeutic outcome. The increase of frequency efficiently reduced the primary tumor recurrence and alleviated metastasis. The present study suggested that the mechanism involves multiple PTT cycles inhibiting the proliferation of primary tumor cells and stimulating the systematic immune response in the mouse breast cancer model. Therefore, frequency optimization in photothermal ablation may provide a promising strategy to enhance the therapeutic outcome in cancer therapy.

Injectable Thermosensitive Hydrogel Containing Erlotinib-Loaded Hollow Mesoporous Silica Nanoparticles as a Localized Drug Delivery System for NSCLC Therapy.

Erlotinib (ERT), oral administration agents, is one of the most pivotal targeted drugs in the treatment of non-small cell lung cancer (NSCLC); however, its poor solubility, low oral bioavailability, and capricious toxicity limit broader clinical applications. In this paper, a novel injectable matrix is prepared based on hollow mesoporous silica nanoparticles (HMSNs) and thermosensitive poly(d,l-lactide)-poly(ethylene glycol)-poly(d,l-lactide) (PDLLA-PEG-PDLLA, PLEL) hydrogel to encapsulate and localize the sustained release of ERT for improved efficacy against NSCLC. The test-tube-inversion method shows that this ERT-loaded hydrogel composite (ERT@HMSNs/gel) presents as an injectable flowing solution under room temperature and transfers into a physically crosslinked non-flowing gel structure at physiological temperature.The ERT@HMSNs/gel composite shows a much longer intratumoral and peritumoral drug retention by in vivo imaging study. Notably, this injectable drug delivery system (DDS) provides an impressive balance between antitumor efficacy and systemic safety in a mice xenograft model. The novel ERT loaded HMSNs/gel system may be a promising candidate for the in situ treatment of NSCLC. Moreover, this study provides a prospective platform for the design and fabrication of a nano-scaled delivery system for localized anticancer therapies.

Polymeric Nanoparticles with ROS-Responsive Prodrug and Platinum Nanozyme for Enhanced Chemophotodynamic Therapy of Colon Cancer.

The combination of chemotherapy and photodynamic therapy (PDT) has promising potential in the synergistic treatment of cancer. However, chemotherapy and photodynamic synergistic therapy are impeded by uncontrolled chemotherapeutics release behavior, targeting deficiencies, and hypoxia-associated poor PDT efficacy in solid tumors. Here, a platinum nanozyme (PtNP) loaded reactive oxygen species (ROS)-responsive prodrug nanoparticle (CPT-TK-HPPH/Pt NP) is created to overcome these limitations. The ROS-responsive prodrug consists of a thioketal bond linked with camptothecin (CPT) and photosensitizer-2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH). The PtNP in CPT-TK-HPPH/Pt NP can efficiently catalyze the decomposition of hydrogen peroxide (H2O2) into oxygen to relieve hypoxia. The production of oxygen can satisfy the consumption of HPPH under 660 nm laser irradiation to attain the on-demand release of CPT and ensure enhanced photodynamic therapy. As a tumor diagnosis agent, the results of photoacoustic imaging and fluorescence imaging for CPT-TK-HPPH/Pt NP exhibit desirable long circulation and enhanced in vivo targeting. CPT-TK-HPPH/Pt NPs effectively inhibit tumor proliferation and growth in vitro and in vivo. CPT-TK-HPPH/Pt NP, with its excellent ROS-responsive drug release behavior and enhanced PDT efficiency can serve as a new cancer theranostic agent, and will further promote the research of chemophotodynamic synergistic cancer therapy.