Endowing Porphyrinic Metal-Organic Frameworks with High Stability by a Linker Desymmetrization Strategy.

The fabricating of metal-organic frameworks (MOFs) that integrate high stability and functionality remains a long-term pursuit yet a great challenge. Herein, we develop a linker desymmetrization strategy to construct highly stable porphyrinic MOFs, namely, USTC-9 (USTC represents the University of Science and Technology of China), presenting the same topological structure as the well-known PCN-600 that readily loses crystallinity in air or upon conventional activation. For USTC-9, the involved porphyrinic linker (TmCPP-M) with carboxylate groups located in the meta-position presents a chair-shaped conformation with lower C2h symmetry than that (D4h) of the common porphyrinic carboxylate (TCPP) linker in PCN-600. As a result, the wrinkled and interlocked linker arrangements collectively contribute to the remarkable stability of USTC-9. Given the high stability and porosity as well as Lewis acidity, USTC-9(Fe) demonstrates its excellent performance toward catalytic CO2 cycloaddition with diverse epoxides at moderate temperature and atmospheric pressure.

Characterization of a novel phage vB_Pae_HB2107-3I that infects Pseudomonas aeruginosa.

Bacteriophages are potential antibiotic substitutes for the treatment of antibiotic resistant bacteria. Here, we report the genome sequences of a double-stranded DNA podovirus vB_Pae_HB2107-3I against clinical multi-drug resistant Pseudomonas aeruginosa. Phage vB_Pae_HB2107-3I remained stable over a wide range of temperatures (37-60 °C) and pH values (pH 4-12). At MOI of 0.01, the latent period of vB_Pae_HB2107-3I was 10 min, and the final titer reached about 8.1 × 109 PFU/mL. The vB_Pae_HB2107-3I genome is 45,929 bp, with an average G + C content of 57%. A total of 72 open reading frames (ORFs) were predicted, of which 22 ORFs have a predicted function. Genome analyses confirmed the lysogenic nature of this phage. Phylogenetic analysis revealed that phage vB_Pae_HB2107-3I was a novel member of Caudovirales infecting P. aeruginosa. The characterization of vB_Pae_HB2107-3I enrich the research on Pseudomonas phages and provide a promising biocontrol agent against P. aeruginosa infections.

NIR Activated Multimodal Therapeutics Based on Metal-Phenolic Networks-Functionalized Nanoplatform for Combating against Multidrug Resistance and Metastasis.

Multidrug resistance (MDR) and metastasis in cancer have become increasingly serious problems since antitumor efficiency is greatly restricted by a single therapeutic modality and the insensitive tumor microenvironment (TME). Herein, metal-phenolic network-functionalized nanoparticles (t-P@TFP NPs) are designed to realize multiple therapeutic modalities and reshape the TME from insensitive to sensitive under multimodal imaging monitoring. After a single irradiation, a near-infrared laser-activated multistage reaction occurs. t-P@TFP NPs trigger the phase transition of perfluoropentane (PFP) to release tannic acid (TA)/ferric ion (Fe3+ )-coated paclitaxel (PTX) and cause hyperthermia in the tumor region to efficiently kill cancer cells. Additionally, PTX is released after the disassembly of the TA-Fe3+ film by the abundant adenosine triphosphate (ATP) in the malignant tumor, which concurrently inhibits ATP-dependent drug efflux to improve sensitivity to chemotherapeutic agents. Furthermore, hyperthermia-induced immunogenic cell death (ICD) transforms "cold" tumors into "hot" tumors with the assistance of PD-1/PD-L1 blockade to evoke antitumor immunogenicity. This work carefully reveals the mechanisms underlying the abilities of these multifunctional NPs, providing new insights into combating the proliferation and metastasis of multidrug-resistant tumors.

Expression of a Phage-Encoded Gp21 Protein Protects Pseudomonas aeruginosa against Phage Infection.

There is a continuously expanding gap between predicted phage gene sequences and their corresponding functions, which has largely hampered the development of phage therapy. Previous studies reported several phage proteins that could interfere with the intracellular processes of the host to obtain efficient infection. But few phage proteins that protect host against phage infection have been identified and characterized in detail. Here, we isolate a phage, vB_Pae_QDWS, capable of infecting Pseudomonas aeruginosa PAO1 and report that its encoded Gp21 protein protects PAO1 against phage infection. Expression of Gp21 regulates bacterial quorum sensing with an inhibitory effect in low cell density and an activation effect in high cell density. By testing the type IV pilus (TFP)-mediated twitching motility and transmission electron microscopy analysis, Gp21 was found to decrease the pilus synthesis. Further, by constructing the TFP synthesis gene pilB mutant and performing adsorption and phage resistance assay, we demonstrated that the Gp21 protein could block phage infection via decreasing the TFP-mediated phage adsorption. Gp21 is a novel protein that inhibits phage efficacy against bacteria. The study deepens our understanding of phage-host interactions. IMPORTANCE The majority of the annotated phage genes are currently deposited as "hypothetical protein" with unknown function. Research has revealed that some phage proteins serve to inhibit or redirect the host intracellular processes for phage infection. Conversely, we report a phage encoded protein Gp21 that protects the host against phage infection. The pathways that Gp21 involved in antiphage defense in Pseudomonas aeruginosa PAO1 interfere with quorum sensing and decrease type IV pilus-mediated phage adsorption. Gp21 is a novel protein with a low sequence homology with other reported twitching inhibitory proteins. As a lytic phage-derived protein, Gp21 expression protects P. aeruginosa PAO1 from reinfection by phage vB_Pae_QDWS, which may explain the well-known pseudolysogeny caused by virulent phages. Our discoveries provide valuable new insight into phage-host evolutionary dynamics.

RetS Regulates Phage Infection in Pseudomonas aeruginosa via Modulating the GacS/GacA Two-Component System.

In Pseudomonas aeruginosa, the complex multisensing regulatory networks RetS-GacS/GacA have been demonstrated to play key roles in controlling the switch between planktonic and sessile lifestyles. However, whether this multisensing system is involved in the regulation of phage infection has not been investigated. Here, we provide a link between the sensors RetS/GacS and infection of phages vB_Pae_QDWS and vB_Pae_W3. Our data suggest that the sensors kinases RetS and GacS in Pseudomonas aeruginosa play opposite regulatory functions on phage infection. Mutation in retS increased phage resistance. Cellular levels of RsmY and RsmZ increased in PaΔretS and were positively correlated with phage resistance. Further analysis demonstrated that RetS regulated phage infection by affecting the type IV pilus (T4P)-mediated adsorption. The regulation of RetS on phage infection depends on the GacS/GacA two-component system and is likely a dynamic process in response to environmental signals. The findings offer additional support for the rapid emergence of phage resistance. IMPORTANCE Our knowledge on the molecular mechanisms behind bacterium-phage interactions remains limited. Our study reported that the complex multisensing regulatory networks RetS-GacS/GacA of Pseudomonas aeruginosa PAO1 play key roles in controlling phage infection. The main observation was that the mutation in RetS could result in increased phage resistance by reducing the type IV pilus-mediated phage adsorption. The bacterial defense strategy is generally applicable to various phages since many P. aeruginosa phages can use type IV pilus as their receptors. The results also suggest that the phage infection is likely to be regulated dynamically, which depends on the environmental stimuli. Reduction of the signals that RetS favors would increase phage resistance. Our study is particularly remarkable for uncovering a signal transduction system that was involved in phage infection, which may help in filling some knowledge gaps in this field.

Characterization of the newly isolated phage Y3Z against multi-drug resistant Cutibacterium acnes.

Cutibacterium acnes (C. acnes) is a symbiotic bacterium that plays an important role in the formation of acn e inflammatory lesions. As a common component of the acne microbiome, C. acnes phages have the potential to make a significant contribution to treating antibiotic-resistant strains of C. acnes. However, little is known about their genetic composition and diversity. In this study, a new lytic phage, Y3Z, infecting C. acne, was isolated and characterized. Electron microscopy analysis revealed this phage is a siphovirus. Phage Y3Z is composed of 29,160 bp with a GC content of 56.32%. The genome contains 40 open reading frames, 17 of which had assigned functions, while no virulence-related genes, antibiotic resistance genes or tRNA were identified. The one-step growth curve showed the burst size was 30 PFU (plaque-forming unit)/cell. And it exhibited tolerance over a broad range of pH and temperature ranges. Phage Y3Z could infect and lyse all C. acnes isolates tested, though the host range of PA6 was restricted to C. acnes. Based on the phylogenetic and comparative genomic analyses, Y3Z may represent a new siphovirus infecting C. acnes. Characterization of Y3Z will enrich our knowledge about the diversity of C. acnes phages and provide a potential arsenal for thetreatment of acne infection.

Complete genome analysis and biological characterization of a novel phage vB_CP_qdyz_P5 with lytic activity against Clostridium perfringens.

Clostridium perfringens, a common foodborne pathogen, exhibit high-stress resistance. The prevailing reliance on antibiotics in the farming industry for its prevention and control has led to increasing concerns over antibiotic residue and bacterial resistance. Bacteriophages that possess specific lytic activity against C. perfringens are of significant interest. Here, a novel C. perfringens phage, named vB_CP_qdyz_P5, was isolated and characterized. The phage displayed high stability at temperatures below 70 °C and pH levels ranging from 4 to 12. Genome analysis revealed that vB_CP_qdyz_P5 has a double-stand DNA of 18,888 bp with a G + C composition of 28.8%. Among the 27 identified opening reading frames (ORFs), eight were found to be functional genes. BLASTn analysis showed that vB_CP_qdyz_P5 is closely related to phage DCp1, with a genome homology coverage of 83%. Phylogenetic analysis indicated that vB_CP_qdyz_P5 may be a novel phage of the family Guelinviridae, Susfortunavirus. This study provides important preliminary information for further research on the potential use of vB_CP_qdyz_P5 in protecting against C. perfringens and maintaining intestinal health.

Genomic analysis and biological properties of the novel Serratia liquefaciens phage vB_SlqM_MQ-4.

A novel lytic Serratia liquefaciens phage, named vB_SlqM_MQ-4, was isolated from sewage. BLASTn analysis showed that the genome sequence of phage vB_SlqM_MQ-4 shared only 15% query coverage with that of Escherichia phage vB_EcoM-ep3, with 80.52% identity. Genomic analysis demonstrated that phage vB_SlqM_MQ-4 has a 43,534-bp dsDNA genome with 56% GC content and might be a member of a new genus in the order Caudoviricetes. Moreover, vB_SlqM_MQ-4 exhibited strong lytic performance with a short latent period (10 min) and a high burst size (267 PFU per cell) as well as a wide range of thermal (below 70 ℃) and pH tolerance (pH 4-12).

Phage resistance of Salmonella enterica obtained by transposon Tn5-mediated SefR gene silent mutation.

Salmonella enterica contamination is a primary cause of global food poisoning. Using phages as bactericidal alternatives to antibiotics could confront the issue of drug resistance. However, the problem of phage resistance, especially mutant strains with multiple phage resistance, is a critical barrier to the practical application of phages. In this study, a library of EZ-Tn5 transposable mutants of susceptible host S. enterica B3-6 was constructed. After the infestation pressure of a broad-spectrum phage TP1, a mutant strain with resistance to eight phages was obtained. Analysis of the genome resequencing results revealed that the SefR gene was disrupted in the mutant strain. The mutant strain displayed a reduced adsorption rate of 42% and a significant decrease in swimming and swarming motility, as well as a significantly reduced expression of the flagellar-related FliL and FliO genes to 17% and 36%, respectively. An uninterrupted form of the SefR gene was cloned into vector pET-21a (+) and used for complementation of the mutant strain. The complemented mutant exhibited similar adsorption and motility as the wild-type control. These results suggest that the disrupted flagellar-mediated SefR gene causes an adsorption inhibition, which is responsible for the phage-resistant phenotype of the S. enterica transposition mutant.

Expansion of the Plaquing Host Range and Improvement of the Absorption Rate of a T5-like Salmonella Phage by Altering the Long Tail Fibers.

The high host specificity of phages is a real challenge in the therapy applications of the individual phages. This study aimed to edit the long tail fiber proteins (pb1) of a T5-like phage to obtain the engineered phages with expanded plaquing host range. Two T5-like Salmonella phages with high genome sequence homology but different plaquing host ranges, narrow-host range phage vB STyj5-1 (STyj5-1) and wide-host range phage vB BD13 (BD13), were isolated and characterized. The pb1 parts of STyj5-1 were replaced by the corresponding part of BD13 using homologous recombination method to obtain the engineered phages. The alterations of the whole pb1 part or the N-terminal amino acids 1-400 of pb1 of STyj5-1 could expand their plaquing host ranges (from 20 strains to 30 strains) and improve their absorption rates (from 0.28-28.84% to 28.10-99.49%). Besides, the one-step growth curves of these engineered phages with modified pb1 parts were more similar to that of STyj5-1. The burst sizes of phages BD13, STyj5-1 and the engineered phages were 250, 236, 166, and 223 PFU per cell, respectively. The expanded plaquing host range and improved absorption rates of these engineered phages revealed that the pb1 part might be the primary determinant of the host specificities of some T5-like phages. IMPORTANCE Genetic editing can be used to change or expand the host range of phages and have been successfully applied in T2, T4 and other phages to obtain engineered phages. However, there are hardly any similar reports on T5-like phages due to that the determinant regions related to their host ranges have not been completely clarified and the editing of T5-like phages is more difficult compared to other phages. This study attempted and successfully expanded the host range of a narrow-host range T5-like phage (STyj5-1) by exchanging its whole pb1 part or the N-terminal 1-400aa of that part by a broad-host range phage (BD13). These demonstrated the pb1 part might be the primary determinant of the host specificities for some T5-like phages and provided an effective method of extension plaquing host range of these phages.

Complete genome analysis of the newly isolated Vibrio phage vB_VpP_WS1 of the family Microviridae.

Here, we describe the characterization and genome annotation of the newly isolated lytic Vibrio parahaemolyticus phage vB_VpP_WS1, isolated from sewage samples collected in Qingdao, China. Transmission electron microscopy revealed that vB_VpP_WS1 is about 22 nm in size and that the virions are isometric, likely icosahedral, particles similar to those of members of the Microviridae. The digestion patterns of phage nucleic acids and whole-genome sequencing analysis together revealed that phage vB_VpP_WS1 has a single-stranded DNA genome of 5564 nt. Eight open reading frames were identified, only four of which could be annotated. The proteins of vB_VpP_WS1 displayed low sequence similarity to their homologs encoded by other microviruses. Phylogenetic analysis based on the major capsid protein suggested that vB_VpP_WS1 is a tentative new member of the family Microviridae.

Complete genome analysis of the novel Shewanella phage vB_Sb_QDWS.

We present here the results of the analysis of the complete genome sequence of a potentially temperate phage, vB_Sb_QDWS, which was isolated from wastewater samples collected in Qingdao, China. The genome of phage vB_Sb_QDWS is composed of a double-stranded DNA that is 47,902 bp in length with a G + C content of 63.16%. It is predicted to contain 69 putative protein-encoding genes. Microscopic and genomic analysis showed that vB_Sb_QDWS is a novel phage of the class Siphoviridae.

Complete genome analysis of the novel Alcaligenes faecalis phage vB_AfaP_QDWS595.

A novel lytic phage named vB_AfaP_QDWS595 infecting Alcaligenes faecalis was isolated and characterized in this study. The genome of phage vB_AfaP_QDWS595 was sequenced and analyzed, and the result revealed that the phage contained 70,466 bp of double-stranded DNA with 41.12% GC content. There were 74 putative genes encoding proteins as well as 11 tRNAs predicted in the phage genome. Phenotype and phylogeny analysis indicated that this phage might be a new member of the family Schitoviridae.

Study on Volatile Chemicals as Spoilage Indexes of Salmon by HS-SPME-GC-MS Technique during Non-Frozen Storage.

Freshness is the most fundamental and important factor to assess raw fish quality. The purpose of our study was to determine the potential spoilage indexes of salmon during non-frozen storage by using headspace solid-phase microextraction (HS-SPME) followed by gas chromatography-mass spectrometry (GC-MS). More than 300 volatile compounds in salmon were detected when sensory scores declined gradually following the quality changes of salmon at different temperatures. And there were 27 and 31 compounds that showed concentration variations when stored at 4 °C and 25 °C, respectively. Among them, the contents of 1,3-di-tert-butylbenzene, acetic acid, and 3-methyl-1-butanol increased significantly in the later storage period and were in accordance with the salmon's qualities. The present study provides valuable information on the volatile chemical spoilage indexes that are closely related to the freshness of salmon, which may provide an efficient alternative way for quality evaluation of salmon.

A retrospective cohort study of obstetric complications and birth outcomes in women with polycystic ovarian syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women and a high risk factor for adverse pregnancy complications. Therefore, we aimed to analyse the relationship between PCOS and pregnancy complications in a large sample from China. Additionally, since obesity and assisted reproductive technology (ART) are common in women with PCOS, we also aimed to determine whether both of these factors increased the complication incidence for women with PCOS. A retrospective cohort study that included 1357 pregnant women with PCOS and 6940 without PCOS was performed. Our results indicated women with PCOS had higher incidence of gestational diabetes mellitus (GDM), hypertension, postpartum haemorrhage, preterm birth, macrosomia and cervical incompetence. Additionally, obesity was associated with an increased incidence of hypertension and GDM in women with PCOS generally. ART did not result in an increase in the obstetric complication rate in women with PCOS. In conclusion, PCOS appeared to result in an increased risk of adverse pregnancy complications. Obesity may further increase the risks of hypertension and GDM among women with PCOS. However, ART did not increase the risk of pregnancy complications, which suggests that ART is a relatively safe and effective method to address infertility problems in women with PCOS.IMPACT STATEMENTWhat is already known on this subject? There are several studies evaluating the associations of PCOS with the risk of pregnancy complications. However, reports about the risk of pregnancy complications between PCOS women with and without obesity or ART are limited.What do the results of this study add? PCOS appeared to increase the risk of adverse pregnancy complications, including GDM, pregnancy-induced hypertension, postpartum haemorrhage, preterm birth, macrosomia and cervical incompetence. Obesity further increased the risks of hypertension and GDM in women with PCOS, but it did not increase the incidence of macrosomia and postpartum haemorrhage. Additionally, ART did not increase the risk of adverse pregnancy complications among women with PCOS, except for postpartum haemorrhage.What are the implications of these findings for clinical practice and/or further research? This study contributes to the literature because it showed that PCOS independently increased the risk of adverse pregnancy complications in a large sample of patients. Second, obesity is a high risk factor for adverse complications in pregnant women with PCOS. Third, ART is a relatively safe and effective method for addressing infertility problems for women with PCOS.

Complete genome sequence of the extreme-pH-resistant Salmonella bacteriophage αα of the family Microviridae.

A novel Salmonella bacteriophage (phage), named αα, was the first reported member of the family Microviridae to exhibit tolerance to both extreme acidic and alkaline conditions (pH 2-12 for 1 h). Phage αα has a circular single-stranded DNA genome of 5,387 nt with a G+C content of 44.66%. A total of 11 putative gene products and no tRNA genes are encoded in the phage αα genome. Whole-genome sequence comparisons revealed that phage αα shares 95% identity with coliphage phiX174 and had a close evolutionary relationship to the phages NC1 and NC7. Phylogenetic analysis of the structural proteins of phage αα and 18 other phiX174-like phages showed that a phylogenetic tree based on protein B sequences had a topology similar to that obtained using whole genome sequences. In addition, variable sites in proteins F and G distributed on the surface of the mature capsid and the conserved protein J were probably involved in maintaining the structural integrity of the phage under extreme pH conditions. Our findings could open up new perspectives for identifying more extreme-pH-resistant phages and their structural proteins and understanding the mechanism of phage adaptation and evolution under extreme environmental stress.

Prolapsed submucosal pyomyoma postpartum, a rare complication of fibroids.

BACKGROUND: Pyomyoma is an unusual fibroid that usually develops during the puerperal or postmenopausal period. If not promptly diagnosed and treated, it can become life threatening. Although various conservative and surgical therapies have been discussed in the literature for this condition, there are very few reports related to the management of prolapsed pedunculated submucosal myoma. CASE PRESENTATION: In this case report, an intramural fibroid transformed into a pedunculated submucosal pyomyoma, which prolapsed into the vagina after a miscarriage and caused life-threatening toxic shock. Apart from prompt antibiotic treatment, a transabdominal myomectomy rather than hysterectomy was performed due to the very large diameter of the pyomyoma. As a result, fertility was preserved, and the patient conceived naturally and delivered a healthy baby two years later. DISCUSSION AND CONCLUSIONS: It is important to maintain strong clinical suspicion for pregnant or postpartum women with a triad of pain, sepsis without an obvious source and a known diagnosis of leiomyoma. Timely recognition and prompt surgical treatment with antibiotics are necessary and could conserve the uterus for future fertility.

Struma ovarii and peritoneal strumosis during pregnancy.

BACKGROUND: Struma ovarii is a special type of ovarian dermoid cyst and accounts for approximately 2-3 % of all dermoid tumours. Benign struma ovarii may manifest as distant metastasis, called peritoneal strumosis, which makes it biologically similar to malignancy, and has been reported in limited cases but never discovered during pregnancy. CASE PRESENTATION: We report a patient with a history of right struma ovarii cystectomy. During pregnancy, pelvic masses with non-specific clinical presentation were found again. During the caesarean section, contralateral struma ovarii with dissemination of nodules in the peritoneal cavity was found, and pathology revealed that the masses were thyroid follicle ovarian goitres. DISCUSSION AND CONCLUSIONS: Recurrent benign struma ovarii with extraovarian dissemination is a rare aggressive clinical manifestation different from malignancy. It is emphasized that adequate assessment and complete resection of suspicious masses are of great importance.

Pregnancy outcomes of Chinese women undergoing IVF with embryonic cryopreservation as compared to natural conception.

BACKGROUND: To examine differences in the maternal characteristics and pregnancy outcomes of Chinese women with various causes of infertility who underwent in vitro fertilization (IVF) with embryonic cryopreservation treatment. METHODS: Cases were pregnancies after IVF-ET with embryonic cryopreservation; controls were spontaneously conceived pregnancies. Subgroup analysis was carried out according to etiology of infertility. The IVF treatment group was divided into 5 subgroups according to infertility etiology as follows: ovulation disorder, tubal disease, male infertility, endometriosis, and mixed infertility. Data on demographic characteristics, medical history, laboratory tests, and delivery were reviewed. Logistic regression analysis was performed for pregnancy and perinatal complications and neonatal outcomes. The multivariable model was adjusted for potential confounders. RESULTS: Among singleton pregnancies, compared with spontaneous pregnancies, IVF pregnancies were associated with significant increases in the rates of the following: gestational diabetes mellitus (GDM) (aOR 1.76[95% CI 1.33-2.33]), preeclampsia (2.60[1.61-4.20]), preterm preeclampsia (4.52[2.03-10.06]), postpartum hemorrhage (1.57[1.04-2.36]), intrahepatic cholestasis of pregnancy (3.84[1.06-13.94]), preterm premature rupture of membranes (2.11[1.17-3.81]), preterm birth (1.95[CI 1.26-3.01]), low birthweight (1.90[1.13-3.20]), macrosomia (1.53[1.03-2.27]), and neonatal intensive care unit (NICU) admission (1.69[1.22-2.34]) in the ovulation disorder group; GDM (1.50[1.21-1.86]), placenta previa (2.70[1.59-4.59]), placenta accreta (1.78[1.10-2.89]), postpartum hemorrhage (1.61[1.19-2.18]), macrosomia (1.60[1.21-2.13]) and 5-min Apgar score ≤ 7 (4.09[1.04-16.08]) in the tubal disease group; placenta previa (9.33[4.22-20.62]), small for gestational age (2.29[1.04-5.08]), macrosomia (2.00[1.02-3.95]) and NICU admission (2.35[1.35-4.09]) in the endometriosis group; placenta previa (4.14[2.23-7.68]) and placenta accreta (2.05[1.08-3.87]) in the male infertility group; and GDM (1.85[1.15-2.98]), placenta previa (4.73[1.83-12.21]), placental abruption (3.39[1.20-9.56]), chorioamnionitis (2.93[1.04-8.26]), preterm birth (2.69[1.41-5.15]), and 1-min Apgar score ≤ 7 (4.68[1.62-13.51]) in the mixed infertility group. Among multiple pregnancies, most of the differences that were significant in singleton pregnancies were less extensive or had disappeared. CONCLUSIONS: Infertility etiology within the IVF population was found to affect maternal and neonatal outcomes among all births. During the perinatal period, infertility etiology appears to be an additional risk factor for abnormal pregnancy outcomes besides the use of IVF techniques compared with spontaneous pregnancies. Higher risk was found for ovulation disorders, and lower risk was found for male infertility.

Hypoxia modulation by dual-drug nanoparticles for enhanced synergistic sonodynamic and starvation therapy.

BACKGROUND: Sonodynamic therapy (SDT) is an emerging non-invasive therapeutic technique. SDT-based cancer therapy strategies are presently underway, and it may be perceived as a promising approach to improve the efficiency of anti-cancer treatment. In this work, multifunctional theranostic nanoparticles (NPs) were synthesized for synergistic starvation therapy and SDT by loading glucose oxidase (GOx, termed G) and 5,10,15,20-tetrakis (4-chlorophenyl) porphyrin) Cl (T (p-Cl) PPMnCl, termed PMnC) in Poly (lactic-co-glycolic) acid (PLGA) NPs (designated as MG@P NPs). RESULTS: On account of the peroxidase-like activity of PMnC, MG@P NPs can catalyze hydrogen peroxide (H2O2) in tumor regions to produce oxygen (O2), thus enhancing synergistic therapeutic effects by accelerating the decomposition of glucose and promoting the production of cytotoxic singlet oxygen (1O2) induced by ultrasound (US) irradiation. Furthermore, the NPs can also serve as excellent photoacoustic (PA)/magnetic resonance (MR) imaging contrast agents, effectuating imaging-guided cancer treatment. CONCLUSION: Multifunctional MG@P NPs can effectuate the synergistic amplification effect of cancer starvation therapy and SDT by hypoxia modulation, and act as contrast agents to enhance MR/PA dual-modal imaging. Consequently, MG@P NPs might be a promising nano-platform for highly efficient cancer theranostics.