Targeting N-doped graphene quantum dot with high photothermal conversion efficiency for dual-mode imaging and therapy in vitro.

A graphene quantum dot (GQD) is a novel carbon nanomaterial with the advantages of low cost and no pollution. It has attracted serious attention in the biomedical fields because of its stabilities and tunable fluorescence wavelength. In this manuscript, an N-doped graphene quantum dot (N-GQD) was synthesized by a hydrothermal method using citric acid as the carbon source and urea as the nitrogen source. X-ray diffraction, Raman spectroscopy, transmission electron microscopy, UV-vis absorption spectrum, and fluorescence spectrum were used to characterize the N-GQD. The results showed that the N-GQD had a uniform size of about 5 nm. The two fluorescence emission peaks, one in the visible light region showed a 49.75% quantum yield, while another in the near infrared region was 2.49%. The photothermal conversion efficiency was 62.53%, higher than any kind of carbon nanomaterial in existence today. MTT and a long-term cytotoxicity experiment confirmed that the N-GQD had low cytotoxicity. The probe also had the ability of photoacoustic response at the same time. After coupling with folic acid, it presented imaging and photothermal therapy on the cells, which has great application prospects in the early diagnosis and treatment of tumors.

Folic acid modified Pluronic F127 coating Ag2S quantum dot for photoacoustic imaging of tumor cell-targeting.

In this study, an oil-soluble Ag2S quantum dot (QD) was synthesized through thermal decomposition using the single-source precursor method, and Pluronic F127 (PF127), a triblock copolymer functionalized with folic acid (FA), was deposited on the surface of the QD, then a water-soluble PF127-FA@Ag2S nanoprobe with targeting ability was fabricated. The as-prepared PF127-FA@Ag2S exhibited spheroidal morphology and high dispersibility, with average diameters of 115 ± 20.7 nm (as observed by transmission electron microscopy). No obvious toxicity of the PF127-FA@Ag2S nanoprobe was found in standard 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay and colony-formation assay, indicating good biocompatibility and safety. The resulting PF127-FA@Ag2S exhibited excellent stability between 4 °C-40 °C. Additionally, the capacity of the tumor cell-targeting high contrast enhanced photoacoustic imaging of PF127-FA@Ag2S was verified in comparison with A547 and HeLa cells. In other words, the excellent properties of PF127-FA@Ag2S show great potential in further research for targeting and photoacoustic imaging.

A multifunctional targeting probe with dual-mode imaging and photothermal therapy used in vivo.

BACKGROUND: Ag2S has the characteristics of conventional quantum dot such as broad excitation spectrum, narrow emission spectrum, long fluorescence lifetime, strong anti-bleaching ability, and other optical properties. Moreover, since its fluorescence emission is located in the NIR-II region, has stronger penetrating ability for tissue. Ag2S quantum dot has strong absorption during the visible and NIR regions, it has good photothermal and photoacoustic response under certain wavelength excitation. RESULTS: 200 nm aqueous probe Ag2S@DSPE-PEG2000-FA (Ag2S@DP-FA) with good dispersibility and stability was prepared by coating hydrophobic Ag2S with the mixture of folic acid (FA) modified DSPE-PEG2000 (DP) and other polymers, it was found the probe had good fluorescent, photoacoustic and photothermal responses, and a low cell cytotoxicity at 50 µg/mL Ag concentration. Blood biochemical analysis, liver enzyme and tissue histopathological test showed that no significant influence was observed on blood and organs within 15 days after injection of the probe. In vivo and in vitro fluorescence and photoacoustic imaging of the probe further demonstrated that the Ag2S@DP-FA probe had good active targeting ability for tumor. In vivo and in vitro photothermal therapy experiments confirmed that the probe also had good ability of killing tumor by photothermal. CONCLUSIONS: Ag2S@DP-FA was a safe, integrated diagnosis and treatment probe with multi-mode imaging, photothermal therapy and active targeting ability, which had a great application prospect in the early diagnosis and treatment of tumor.

Water-Soluble Coenzyme Q10 Reduces Rotenone-Induced Mitochondrial Fission.

Parkinson's disease is a neurodegenerative disorder characterized by mitochondrial dysfunction and oxidative stress. It is usually accompanied by an imbalance in mitochondrial dynamics and changes in mitochondrial morphology that are associated with impaired function. The objectives of this study were to identify the effects of rotenone, a drug known to mimic the pathophysiology of Parkinson's disease, on mitochondrial dynamics. Additionally, this study explored the protective effects of water-soluble Coenzyme Q10 (CoQ10) against rotenone-induced cytotoxicity in murine neuronal HT22 cells. Our results demonstrate that rotenone elevates protein expression of mitochondrial fission markers, Drp1 and Fis1, and causes an increase in mitochondrial fragmentation as evidenced through mitochondrial staining and morphological analysis. Water-soluble CoQ10 prevented mitochondrial dynamic imbalance by reducing Drp1 and Fis1 protein expression to pre-rotenone levels, as well as reducing rotenone treatment-associated mitochondrial fragmentation. Hence, water-soluble CoQ10 may have therapeutic potential in treating patients with Parkinson's disease.

[Diagnostic Value of Cystain C in Contrast Associated Acute Kidney Injury after Transcatheter Closure for Children with Congenital Heart Disease].

OBJECTIVES: To investigate the diagnostic value of cystain C (SCys-C) in contrast associated acute kidney injury (AKI) after transcatheter closure for children with congenital heart disease. METHODS: There were 128 children with congenital heart disease (interventricular septal defect or patent ductus arteriosus) underwent transcatheter closure in West China Second University Hospital during 2013. Blood urea nitrogen (BUN), serum creatinine (SCr) and SCys-C were examined before surgery and at 24 and 48 h after surgery. The incidence of AKI was calculated. The children were divided into two groups according to glomerular filtration rate: AKI group (renal function stage 1, renal function stage 2 subgroups) and non-AKI group. Differences in renal function indexes and SCys-C were compared between AKI group ( n=16) and non-AKI group ( n=112), renal function stage 1 and stage 2 subgroups. ROC curve analysis was used to calculate the cut-off value of SCys-C in the diagnosis of AKI . RESULTS: The levels of SCr and SCys-C in AKI group were significantly higher than those in non-AKI group ( P<0.05). However, there was no significant difference in BUN between the two groups ( P>0.05). Only SCys-C had a significant difference between renal function stage 1 and stage 2 subgroups ( P<0.05). The cut-off value of 24 h SCys-C in the diagnosis of AKI was 1.055 mg/L according to area under curve (AUC). AUC indicated that AKI could be diagnosed earlier with SCys-C than SCr ( P<0.05). CONCLUSIONS: The contrast agent could increase the risk of child AKI after transcatheter closure for congenital disease children.SCys-C is an important index for this risk with its cut-off value of 1.055 mg/L at 24 h post-surgery.

Engineering Phage Nanocarriers Integrated with Bio-Intelligent Plasmids for Personalized and Tunable Enzyme Delivery to Enhance Chemodynamic Therapy.

Customizable and number-tunable enzyme delivery nanocarriers will be useful in tumor therapy. Herein, a phage vehicle, T4-Lox-DNA-Fe (TLDF), which adeptly modulates enzyme numbers using phage display technology to remodel the tumor microenvironment (TME) is presented. Regarding the demand for lactic acid in tumors, each phage is engineered to display 720 lactate oxidase (Lox), contributing to the depletion of lactic acid to restructure the tumor's energy metabolism. The phage vehicle incorporated dextran iron (Fe) with Fenton reaction capabilities. H2O2 is generated through the Lox catalytic reaction, amplifying the H2O2 supply for dextran iron-based chemodynamic therapy (CDT). Drawing inspiration from the erythropoietin (EPO) biosynthetic process, an EPO enhancer is constructed to impart the EPO-Keap1 plasmid (DNA) with tumor hypoxia-activated functionality, disrupting the redox homeostasis of the TME. Lox consumes local oxygen, and positive feedback between the Lox and the plasmid promotes the expression of kelch ECH Associated Protein 1 (Keap1). Consequently, the downregulation of the antioxidant transcription factor Nrf2, in synergy with CDT, amplifies the oxidative killing effect, leading to tumor suppression of up to 78%. This study seamlessly integrates adaptable T4 phage vehicles with bio-intelligent plasmids, presenting a promising approach for tumor therapy.

Identification of Novel NSD1 variations in four Pediatric cases with sotos Syndrome.

OBJECTIVE: Sotos syndrome (SOTOS) is an uncommon genetic condition that manifests itself with the following distinctive features: prenatal overgrowth, facial abnormalities, and intellectual disability. This disorder is often associated with haploinsufficiency of the nuclear receptor-binding SET domain protein 1 (NSD1)gene. We investigated four pediatric cases characterized by early-onset overgrowth and developmental delay. The primary objective of this study was to achieve accurate genetic diagnoses. DESIGN&METHODS: A sequential analysis approach comprising chromosomal karyotyping, whole exome sequencing, and microarray analysis was conducted. RESULTS: All four cases exhibited variations in the NSD1 gene, with the identification of four previously unreported de novo variants, each specific to one case.Specifically, Case 1 carried the NSD1 (NM_022455): c.2686 C > T(p.Q896X) variant, Case 2 had the NSD1 (NM_022455): c.2858_2859delCT(p.S953X) variant, Case 3 displayed a chromosomal aberration, chr5: 5q35.2q35.3(176,516,604-176,639,249)×1, which encompassed the 5'-untranslated region of NSD1, and Case 4 harbored the NSD1 (NM_022455): c.6397T > G(p.C2133G) variant. CONCLUSION: This study not only provided precise diagnoses for these cases but also supplied significant evidence to facilitate informed consultations. Furthermore, our findings expanded the spectrum of mutations associated with SOTOS.

Simultaneous labeling and multicolor fluorescence imaging of multiple immune cells on liver frozen section by polychromatic quantum dots below freezing points.

A method for simultaneous labeling and multicolor fluorescence imaging of different hepatic immune cells below freezing point is established based on quantum dots. In the experiment, carbon quantum dots with emission wavelength of 435 nm, CdTe@CdS quantum dots at 542 nm and CdSe@ZnS quantum dots at 604 nm are synthesized respectively, it is found that when the mass fractions of KCl (as antifreeze) are 12 %, 14 %, and 12 %, respectively, the three quantum dot dispersion systems remain liquid state at -20 °C. After they are conjugated with the corresponding secondary antibodies, agarose gel electrophoresis, circular dichroism and capillary electrophoresis confirm the effectiveness of conjugation. By indirect immunofluorescence method, the above three quantum dot fluorescent probes are used to simultaneously and specifically target a variety of liver immune cells, and the multi-color simultaneous imaging of different liver immune cells is realized under the same excitation wavelength, it is found that hepatic macrophages are arranged radially in the liver, hepatic stellate cells present punctate distribution, and hepatic sinusoidal endothelial cells present circular distribution, which is consistent with the results of H&E staining and ultrathin section TEM. This study provides an important technical means for elucidating the structure and function of the liver.

Carbon quantum dot fluorescent probe for labeling and imaging of stellate cell on liver frozen section below freezing point.

The targeted labeling imaging of stellate cells on liver frozen section by immunofluorescence is a very promising visualization technique to study the distribution of stellate cells in the liver. In this study, water soluble carbon quantum dots that can emit blue, green and yellow fluorescence are synthesized by the hydrothermal method, and their sizes are 3.2, 3.7, and 4.3 nm, respectively. The three carbon quantum dots have good fluorescence stability, and the quantum yields are 36.1%, 26.3% and 21%, respectively. When the mass fraction of KCl in the blue carbon quantum dot dispersion system is 13%, it still maintains the liquid state at -30 °C. The final fluorescent probe is obtained after the carbon quantum dots are coupled with the secondary antibody, spectral characterizations confirm that the conjugate probe still maintains protein immunoactivity and has good stability. Cell experiments prove that the probe has good biocompatibility, the rabbit anti-mouse Desmin antibody is used as the primary antibody, the results of cellular immunofluorescence imaging and flow cytometry show that the probe can specifically label hepatic stellate cell at -20 °C. The results of liver frozen section experiments show that hepatic stellate cell can be specifically targeted and labeled by the fluorescent probe. This labeling technology provides an important technical means for elucidating the structure and function of the liver at the cellular level, exploring the liver pathological change, and designing and developing drug.

Gelatinase-responsive biodegradable targeted microneedle patch for abscess wound treatment of S. aureus infection.

Abscess wound caused by bacterial infection is usually difficult to heal, thus greatly affect people's quality of life. In this study, a biodegradable drug-loaded microneedle patch (MN) is designed for targeted eradication of S. aureus infection and repair of abscess wound. Firstly, the bacterial responsive composite nanoparticle (Ce6@GNP-Van) with a size of about 182.6 nm is constructed by loading the photosensitizer Ce6 into gelatin nanoparticle (GNP) and coupling vancomycin (Van), which can specifically target S. aureus and effectively shield the phototoxicity of photosensitizer during delivery. When Ce6@GNP-Van is targeted and enriched in the infected regions, the gelatinase secreted by the bacteria can degrade GNP in situ and release Ce6, which can kill the bacteria by generating ROS under laser irradiation. In vivo experiments show that the microneedle is basically degraded in 10 min after inserting into skin, and the abscess wound is completely healed within 13 d after applying Ce6@GNP-Van-loaded MN patch to the abscess wound of the bacterial infected mice with laser irradiation, which can simultaneously achieve the eradication of biofilm and subsequent wound healing cascade activation, showing excellent synergistic antibacterial effect. In conclusion, this work establishes a synergistic treatment strategy to facilitate the repair of chronic abscess wound.

Ischemic colitis after receiving the second dose of a COVID-19 inactivated vaccine: A case report.

BACKGROUND: The outbreak of the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 has been the most important clinical challenge worldwide since January 2020. COVID-19 inactivated vaccines play a crucial role in reducing the rates of morbidity and mortality. CASE SUMMARY: We presented a 48-year-old woman from Haidian District, Beijing, China who developed ischemic colitis after receiving the second dose of COVID-19 inactivated vaccine. Computed tomography of the abdomen showed edema and bowel wall thickening with hypodensity in the sigmoid colon and descending colon. Colonoscopy revealed hyperemia, edema and erosion of the mucosa with superficial ulceration and a yellow-white coating at the descending colon and sigmoid colon. The symptoms were relieved after 1 wk of receiving pinaverium bromide (50 mg, tid) and aspirin enteric-coated tablets (0.1 g, qd). CONCLUSION: The possible occurrence of ischemic colitis should be considered after administration of the COVID-19 inactivated vaccines.

CdTe@CdS quantum dots for labeling and imaging macrophages in liver frozen sections below the freezing point.

CdTe@CdS core-shell quantum dots with different particle sizes are synthesized by an aqueous method, and coating them with a CdS shell layer improves the quantum yield (36% → 59%) and fluorescence stability (37% → 77%) of CdTe@CdS quantum dots. When the KCl concentration (mass fraction) in the system is 15%, the CdTe@CdS quantum dot dispersion system remains in the liquid state at -20 °C, and the low temperature increases the fluorescence intensity. A QD-Ab probe is obtained after CdTe@CdS quantum dots are coupled with IgG; the circular dichroism shows that the IgG protein structure is not destroyed, while capillary electrophoresis, agarose gel electrophoresis and flow cytometry verify the conjugation efficiency. With rabbit anti-mouse EMR1 antibody as the primary antibody and QD-Ab as the secondary antibody, the hepatic macrophages in liver frozen sections are fluorescently labeled at -20 °C, and it is found that they are radially distributed in hepatic sinusoids with specific and highly efficient labeling; these results are verified by H&E staining and TEM. This technology can provide important technical support for in-depth understanding of the distribution of liver immune cells in the liver, and it can further provide a scientific basis to understand the relationship between the liver structure and function and pathological changes.

Multifunctional nanocarrier with self-catalytic production of nitric oxide for photothermal and gas-combined therapy of tumor.

Single treatment often faces the problem that it cannot completely eradicate tumor and inhibit the tumor metastasis. In order to overcome this shortcoming, multi-modal tumor treatment has attracted widespread attention. In the present article, based on ascorbyl palmitate (PA) and l-arginine (l-Arg), a multifunctional nanocarrier is designed for synergetic treatment of tumor with photothermal and nitric oxide (NO) gas therapy. Firstly, PA and l-Arg were self-assembled to form novel functional micelles, PL, with high biosafety using electrostatic interaction and hydrogen bonding. The functional micelles could self-catalyze to produce NO at the tumor site. Then, Ag2S quantum dots having fluorescence imaging and photothermal properties were encapsulated to obtain the nanocarrier, A@PL. The results show that A@PL had a hydrated size of around 78 nm and presented good stability within 30 d. Moreover, in vitro studies indicate that it was efficient with regards to NO self-generating capacity, whereas the photothermal conversion efficiency was as high as 34% under near-infrared light irradiation. The cytotoxicity results show that, when the concentration of A@PL was as high as 2 mM, the survival rate of 3 T3 cells was still 78.23%, proving that the probe has good safety characteristics. Fluorescence imaging results show that its maximum enrichment can be achieved at the tumor site after tail vein injection for 3 h, and out of the body after 24 h, indicating good internal circulation. The in vivo studies show that the rate of inhibition of tumor using the nanocarrier was as high as 98%, and almost overcame the problem of tumor recurrence caused by single treatment, thus presenting a significant tumor treatment effect. This new multifunctional nanocarrier with self-catalytic production of NO provides a new idea for the efficient treatment of tumors.

A self-assembled nanoplatform based on Ag2S quantum dots and tellurium nanorods for combined chemo-photothermal therapy guided by H2O2-activated near-infrared-II fluorescence imaging.

A nanoplatform based on Ag2S quantum dots (QDs) and tellurium nanorods (TeNRs) was developed for combined chemo-photothermal therapy guided by H2O2-activated near-infrared (NIR)-II fluorescence imaging. Polypeptide PC10AGRD-modified TeNRs and Ag2S QDs were co-encapsulated in 4T1 cell membrane to prepare a nanoplatform (CCM@AT). Ag2S QDs and TeNRs in the CCM@AT were used as a fluorescence probe and photosensitizer, and a chemotherapeutic prodrug and quenching agent to quench the fluorescence of Ag2S QDs, respectively. After the CCM@AT was specifically targeted to the tumor site, the TeNRs were dissolved by the high concentration of H2O2 at the tumor site to light up the fluorescence of Ag2S QDs for NIR-II fluorescence imaging. In addition, the generated toxic TeO66- molecules decreased ATP production by selective cancer chemotherapy, which is beneficial for photothermal therapy. The elevated temperature due to photothermal therapy in turn promoted the chemical reaction in chemotherapy. In vitro and in vivo toxicity results showed that the CCM@AT possesses high biocompatibility. Compared to single photothermal therapy and chemotherapy, the synergistic chemo-photothermal therapy can effectively suppress the growth of 4T1 tumor. This all-in-one nanoplatform provides a boulevard for the combination therapy of tumors guided by NIR-II fluorescence imaging. STATEMENT OF SIGNIFICANCE: NIR-II fluorescence imaging shows the characteristics of low tissue absorption, reflection, and scattering, which can greatly reduce the influence of autofluorescence in vivo. However, the non-negligible effect of autofluorescence is still observed in fluorescence imaging in vivo. Therefore, there is an urgent need to develop a strategy of controlled release of fluorescence for accurate imaging and tumor therapy. Here, Ag2S quantum dots (QDs) with NIR-II fluorescence emission and good photothermal conversion efficiency are used as a fluorescence probe and photosensitizer, and tellurium nanorods (TeNRs) are used as a chemotherapeutic prodrug and quenching agent to quench the fluorescence of Ag2S QDs. This multiple nanoplatform provides an inspiration for the combination therapy of tumor guided by NIR-II fluorescence imaging.

Tumor Microenvironment-Activated Theranostics Nanozymes for Fluorescence Imaging and Enhanced Chemo-Chemodynamic Therapy of Tumors.

Chemodynamic therapy (CDT) is widely explored for tumor-specific therapy by converting endogenous H2O2 to lethal ·OH to destroy cancer cells. However, ·OH scavenging by glutathione (GSH) and insufficient intratumoral H2O2 levels seriously hinder the application of CDT. Herein, we reported the fabrication of copper ion-doped ZIF-8 loaded with gold nanozymes and doxorubicin hydrochloride (DOX) for the chemotherapy and CDT synergistic treatment of tumors with the assistance of tumor microenvironment (TME)-activated fluorescence imaging. The Cu2+-doped ZIF-8 shell was gradually degraded to release DOX and gold nanoclusters responding to the acidic TME. The fluorescence signal of the tumor region was acquired after the quenched fluorescence of the gold nanoclusters by Cu2+ and DOX by aggregation-induced quenching was turned on because of the interaction of GSH with Cu2+ and the release of free DOX. The Cu2+ ions could deplete the GSH via redox reactions and the generated Cu+ could convert internal H2O2 to ·OH for tumor CDT. The chemotherapeutic effect of DOX was strengthened through drug efflux inhibition and drug sensitivity increase due to the consumption of GSH and ·OH burst. Moreover, DOX could raise the level of H2O2 and augment the effect of CDT. In addition, the fluorescent gold nanoclusters not only served as a peroxidase to convert H2O2 to ·OH but also employed as an oxidase to consume GSH, resulting in the amplification of chemotherapy and CDT. This work presents an approach to construct tumor microenvironment-activated theranostic probes without external stimuli and to achieve the tumor elimination through cascade reactions and synergistic treatment.

Labeling of liver cells with CdSe/ZnS quantum dot-based fluorescence probe below freezing point.

In this paper, CdSe/ZnS quantum dots (QDs) with particle size of 5.5 ~ 9.3 nm were synthesized, and the fluorescence emission ranged from 545 ~ 616 nm. When the volume fraction of ethanol was 30%, the water-soluble QD dispersion system remained liquid under -20 °C freezing conditions, the fluorescence intensity increased with a decrease in temperature, and the quantum yield reached 79% at -20 °C. The endothelial cell adhesion molecule CD31 antibody (anti-CD31) was used as the primary antibody, QDs were coupled with IgG as the secondary antibody (QD-Ab), and effective labeling of hepatic sinusoid endothelial cells was achieved at -20 °C. Fluorescence imaging and flow cytometry analysis showed that the labeling efficiency was as high as 97%, indicating that QDs have an important application prospect in microscopic section tomography of the liver.

Response of Protective Enzymes in Western Flower Thrips (Thysanoptera: Thripidae) to Two Leguminous Plants.

The western flower thrips, Frankliniella occidentalis, is a major invasive pest of commercially important crops worldwide. We compared the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) and the expressions of two putative SOD and two putative POD sequences in second instar larvae and adults after three generations of adaptation to kidney bean and broad bean plants. The results showed that the SOD, POD, and CAT activities in adults were significantly higher than those in the second instar larvae. The SOD activities were significantly higher in both the second instar larvae and the adults fed on kidney bean (Phaseolus vulgaris) plants versus broad bean (Vicia faba) plants, whereas the POD and CAT activities showed the opposite trend. The gene expression data showed that the FoPOD-2 expression levels were lower in the second instar larvae after three generations of feeding on broad bean plants versus kidney bean plants. The expression levels of FoSOD-1 and FoSOD-2, and FoPOD-1 under broad bean plant treatment were higher than those under kidney bean plant treatment. Additionally, gene expression fluctuated among the different generations. Our results indicated that western flower thrips demonstrated plasticity in gene expression and activity of protective enzymes, which is related to their adaptability to the host plants. Western flower thrips can change the expression of protective enzyme genes and enzyme activity in vivo to better adapt to kidney bean and broad bean plants.

Injectable polypeptide-engineered hydrogel depot for amplifying the anti-tumor immune effect induced by chemo-photothermal therapy.

The immunosuppressive tumor microenvironment has caused great obstacles to tumor immunotherapy, especially where less tumor-associated antigens are released from tumor sites. Herein, a Ag2S QD/DOX/Bestatin@PC10ARGD genetically engineered polypeptide hydrogel PC10ARGD as a sustained-release material was developed for mammary carcinoma treatment. A near-infrared silver sulfide (Ag2S) QD as a photosensitizer was encapsulated into the hydrophobic cavity formed by the self-assembly of the polypeptide nanogel (PC10ARGD) for photothermal therapy. The water-soluble drug DOX and Bestatin were integrated into the PC10ARGD hydrogel. The photothermal effect could trigger the sustained release of the DOX, which could be applied to initiate in situ vaccination. Bestatin as an immune-adjuvant drug could amplify the body's immune function. The results of in vivo therapy tests exhibited that the Ag2S QD/DOX/Bestatin@PC10ARGD hydrogel with laser irradiation could activate anti-tumor immune effects that inhibit the growth of primary tumors and distal lung metastatic nodules. Meanwhile, a safer lower-temperature with multiple laser irradiation treatment strategy exhibited more effective tumor-killing performance (84.4% tumor inhibition rate) and promoted the penetration of immune cells into the tumor tissue. The CD8+ and CD4+ cytotoxic T cells ratio was increased by 5.3 and 10 times, respectively, thus exhibiting a good prognostic signal. The multifunctional polypeptide hydrogel as a green manufacturing and engineering material is promising to serve as a cancer vaccine for anticancer applications.

A pH/Ultrasound dual-response biomimetic nanoplatform for nitric oxide gas-sonodynamic combined therapy and repeated ultrasound for relieving hypoxia.

Sonodynamic therapy (SDT) has rapidly developed as a powerful alternative to traditional photodynamic therapy due to its intrinsically deeper tissue-penetration. However, single SDT dose is incapable of radical cure because the long-term hypoxia of tumor limits its therapeutic effect. Herein, we developed a biomimetic nanoplatform with dual pH/ultrasound response, homologous targeting and low phototoxicity for combined nitric oxide (NO) gas therapy with SDT to solve the problem. This nanoplatform is composed of zeolite imidazole framework-8 material embedded with nitrosoglutathione (GSNO) and chlorin e6 (Ce6) by one-step encapsulation, and then wrapped by homologous tumor cell membrane. In vitro and in vivo experiments indicate that the biomimetic nanoplatform has excellent biocompatibility and shows higher retention in tumor by homologous targeting. Importantly, it can sustainably release the encapsulated drug in acidic tumor microenvironment and accelerate degradation by ultrasound (US). Furthermore, NO released from GSNO and reactive oxygen species generated by Ce6, which are both triggered by US, react with each other to produce highly reactive peroxynitrite to inhibit the growth of tumor. Moreover, by repeated US irradiation, the tumor hypoxia can be relieved for a much-longer term, resulting in an effective gas-sonodynamic combined treatment. This study fully utilizes the advantages of US, providing a new strategy for high-performance cancer therapy.

ROS-augmented and tumor-microenvironment responsive biodegradable nanoplatform for enhancing chemo-sonodynamic therapy.

Nanocarrier for augmenting the efficacy of reactive oxygen species (ROS) by tumor microenvironment (TME) has become an emerging strategy for cancer treatment. Herein, a smart biodegradable drug delivery nanoplatform with mitochondrial-targeted ability, pH-responsive drug release and enzyme-like catalytic function is designed. This efficient ROS-generating platform uses ultrasound with deeper penetration capability as excitation source for combined chemotherapy and sonodynamic therapy (SDT) of tumor. In vitro experiments show that the nanoplatform can co-load Ce6 and DOX and be degraded in slight acid environment, and the DOX release rate is 63.91 ± 1.67%. In vivo experiments show that the nanoplatform has extremely biosafety and can be enriched in tumor site and excluded from body after 24 h. More significantly, after combined treatment, the tumors are eliminated and the mice still survive healthily without recurrence after 60 d. This is because not only it can achieve mitochondrial targeting and use platinum particle to increase oxygen content in TME to enhance the effect of SDT, but also it can use weak acidic TME to accelerate drug release to achieve the combination of chemotherapy and SDT. The probe provides a new strategy for designing ROS-based nanoplatform for the treatment of malignant tumor.