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The survival rate of flap is a crucial factor for determining the success of tissue repair and reconstruction. Flap transplantation surgery often leads to ischemic and reperfusion injury, causing apoptosis and tissue necrosis, which significantly reduces the survival rate of flap. To address this issue, we developed a porcine skin decellularized matrix gel nanocomplex loaded with alprostadil (Alp) in Prussian blue nanoparticles (PB NPs) called Alp@PB-Gel. This gel not only maintained the cell affinity of the extracellular scaffold but also exhibited a high degree of plasticity. In vitro assays demonstrated that Alp@PB-Gel possessed antioxidant activity, scavenging ROS ability, and effectively promoted the angiogenesis and migration of human vascular endothelial cells (HUVECs) by stimulating the proliferation of vascular epithelial cells and fibroblasts. In vivo assays further confirmed that Alp@PB-Gel could effectively alleviate necrosis in the early and late stages after surgery, downregulate the levels of NLRP3 and CD68 to inhibit apoptosis and attenuate inflammation, while upregulate the levels of VEGF and CD31 to promote vascular tissue regeneration. Moreover, Alp@PB-Gel exhibited excellent cell affinity and biocompatibility, highlighting its potential for clinical application., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Drug-induced immunogenic cell death (ICD) can efficiently inhibit tumor growth and recurrence through the release of tumor-associated antigens which activate both local and systemic immune responses. Pyroptosis has emerged as an effective means for inducing ICD; however, the development of novel pyroptosis inducers to specifically target tumor cells remains a pressing requirement. Herein, we report that Cinobufagin (CS-1), a main ingredient of Chansu, can effectively induce pyroptosis of triple-negative breast cancer (TNBC) cells, making it a potential therapeutic agent for this kind of tumor. However, the application of CS-1 in vivo is extremely limited by the high dosage/long-term usage and non-selectivity caused by systemic toxicity. To address these drawbacks, we developed a new nanomedicine by loading CS-1 into Prussian blue nanoparticles (PB NPs). The nanomedicine can release CS-1 in a photothermal-controlled manner inherited in PB NPs. Furthermore, hybrid membrane (HM) camouflage was adopted to improve the immune escape and tumor-targeting ability of this nanomedicine, as well. In vitro assays demonstrated that the chemo-photothermal combination treatment produced high-level ICD, ultimately fostering the maturation of dendritic cells (DCs). In vivo anti-tumor assessments further indicated that this strategy not only efficiently inhibited primary growth of MDA-MB-231 cells and 4T1 cells-bearing models but also efficiently attenuated distant tumor growth in 4T1 xenograft model. This was mechanistically achieved throuh the promotion of DCs maturation, infiltration of cytotoxic T lymphocyte into the tumor, and the inhibition of Treg cells. In summary, this work provides a novel strategy for efficient TNBC therapy by using nanomaterials-based multimodal nanomedicine through rational design., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Antibiotic therapy can induce the generation of severe bacterial resistance, further challenging the usability of currently available drugs and treatment options. Therefore, it is essential to develop new strategies to effectively eradicate drug-resistant bacteria. Herein, we have reported a combinational strategy for the eradication of drug-resistant bacteria by using chlorin e6 (Ce6) loaded Prussian blue nanoparticles (PB NPs). This nanocomplex showed strong catalase activity and photodynamic properties. In vitro experiments demonstrated that CPB-Ce6 NPs effectively kill MRSA by generating ROS under laser irradiation. Meanwhile, the nano-enzyme activity of CPB NPs can decompose H 2 O 2 in the bacterial microenvironment to upregulate the O 2 level, which in turn alleviates hypoxia in the microenvironment and improves the antibacterial effect of PDT. In vivo results demonstrated that CPB-Ce6 NPs with laser irradiation effectively cleared MRSA and promoted infected wound repair in a diabetic mouse model and normal mice through upregulating VEGF. Moreover, CPB-Ce6 NPs showed excellent biosafety profiles in vitro and in vivo . From our point of view, this PDT based on PB NPs with nano-enzyme activity may provide an effective treatment for infections associated with drug-resistant microbes and tissue repair.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterised by inflammatory micro-environments in the joints. Indomethacin (IND), a conventional nonsteroidal anti-inflammatory drug (NSAID), has been used for the therapy of RA. However, the poor solubility and serious side effects of oral administration of IND significantly limit its efficacy. In this study, we have synthesized biomimetic IND-loaded Prussian blue (PB) nanoparticles (IND@PB@M@HA) with hyaluronic acid (HA) modification for increasing the solubility and targeting the ability of IND to the inflamed joints. The application of hybrid cell membranes on the NPs endowed immune escape of IND@PB@M@HA NPs, which accordingly extended the circulation time in the blood. In vitro assay demonstrated that the combination of nanomedicine and photothermal therapy produced a powerful anti-inflammatory effect by reducing the levels of inflammatory factors and cell viability of activated macrophages and NPs possessed obvious pH-responsiveness. In vivo assay demonstrated that the nanomedicine for synergistic photothermal therapy exhibited desirable pharmacodynamics and pharmacokinetic properties at ultra-low drug dosage in a rat model of adjuvant-induced arthritis, which was confirmed by inflammatory suppression, bone erosion remission, and negligible adverse effects. In summary, the proposed nanomedicine has the potential role for targeted anti-inflammatory therapy of RA.

Human apurinic/pyrimidine endonuclease 1 (APE1) played a critical role in the occurrence, progress and prognosis of tumors through overexpression and subcellular localization. Thus, it has become an important target for enhancing the sensitivity of tumor cells to radiotherapy and chemotherapy. Therefore, detecting and imaging its intracellular activity is of great significance for inhibitor discovery, cancer diagnosis and therapy. In this work, using DNA-based nanoprobe, we developed a new method for monitor intracellular APE1 activity. The detecting system was consisted by single fluorophore labeled hairpin probe and reduced graphene oxide (rGO). The in vitro result showed that a liner response of the detection method ranged from 0.02 U/mL to 2 U/mL with a limit of detection of 0.02 U/mL. Furthermore, this strategy possessing high specificity was successfully applied for APE1-related inhibitor screening using intracellular fluorescence imaging. Panaxytriol, an effective inhibitor of APE1 activity, was screened from traditional Chinese medicine (TCM) and its effect on APE1 activity was monitored in real time in A549 cells. In summary, this sensitive and specific APE1 detection technology is expected to provide an assistance for APE1-related inhibitor screening and diseases diagnosis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A pro-nanodrug combinational strategy for efficient cervical cancer therapy with intrinsic tumor microenvironment (TME)-responsive elements and low side effects is highly desired. Here, a pro-nanodrug complexes with GSH and NIR responsive manner is reported to boost gamabufotalin induced chemo-photothermal therapy with the assistance of reprogrammed TME by indomethacin. In addition, hybrid cell membrane was used to endow nanocomplexes with the prolonging circulation time and high accumulation of drug at tumor tissue. Indomethacin activated by the high level GSH can attenuate tumor inflammation microenvironment triggered by PTT and sensitize tumor cells to gamabufotalin through inhibiting PGE2 secretion. The released low-dose gamabufotalin with low side effects can efficiently kill tumor cells by ROS production and COX-2 low expression. In vitro and in vivo assays demonstrated that strong anti-tumor activity of nanocomplexes in tumor-bearing mice through chemo-photothermal therapy, which was reflected by the eradication of cervical tumor and significant extension of survival time of mice., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Although drug combination has proved to be an efficient strategy for clinic gastric cancer therapy, how to further improve their bioavailability and reduce the side effects are still challenges due to the low solubility and untargeted ability of drugs. Recently, newly emerging nanotechnology has provided an alternative for constructing new drug delivery systems with high targeting ability and solubility. In this study, a pH-responsive liposome (Liposome-PEO, LP) loaded with apatinib (AP) and cinobufagin (CS-1) was used for combinational therapy against gastric cancer after coating with a hybrid membrane (R/C). The results indicated that the constructed nanocomplex LP-R/C@AC not only efficiently killed tumor cells in vitro by inducing apoptosis, autophagy, and pyroptosis, but also significantly inhibited tumor invasion and metastasis via the VEGFR2/STAT3 pathway. Moreover, it showed stronger anti-tumor activity in gastric cancer-bearing mouse models, as compared to the sole drugs. A naturally-derived hybrid cell membrane coating bestowed nanocomplexes with enhanced biointerfacing including prolonged circulation time and targeting ability.

Aim: To investigate the effects of the different morphological characteristics of Prussian blue nanoparticles ( PB NPs) on their biocompatibility and biosafety. Materials & methods: PB NPs with different sizes, shapes and charges were synthesized and their biosafety and biocompatibility performance were systematically compared in vitro and in vivo . Results: Increased size and positive charge of PB NPs adversely affected cell viability, while improving their peroxidase activity and photothermal conversion efficiency. In vivo analysis demonstrated good biocompatibility of PB NPs, without retention in the organs, but increased size retarded their metabolism. Meanwhile, increased size and positive charge adversely affected hepatic and renal function. Conclusion: This comprehensive exploration of biosafety and biocompatibility provides strong evidences for the use of PB NPs as nanodrug carrier and/or imaging agent.

As a breast cancer subtype with high mortality in women, the efficient treatment of Triple-negative breast cancer (TNBC) is still a challenge due to its unique metastatic mode and poor prognosis. In this study, we developed a biomimetic nanodelivery system (denoted as GTDC@M-R NPs) based on erythrocyte membrane (M)-camouflaged graphene oxide quantum dots (GOQDs, G) for TNBC therapy. The TAT (T) and RGD (R) peptides were used to endow targeting accumulation ability of Gamabufotalin (CS-6, C) and doxorubicin (DOX, D) in tumor tissue. In vitro assay indicated good biocompatibility, prolonged blood circulation time (3-fold longer than GT NPs), and effectively enhanced cell and nucleus targeting capability of this nanosystem. Fluorescence activated cell sorter (FACS) analysis indicated that the combination of DOX and CS-6 induced TNBC cell apoptosis more than 89 % under the ratio of 10:1. In vivo assay indicated that the accumulation of GTDC@M-R NPs in tumor sites increased about 2-fold compared to naked GTDC NPs, which was accompanied by high tumor apoptosis rates through blocking chemotherapy-activated cyclooxygenase-2 (COX-2) and enhancing DOX's anti-tumor activity of chemical drugs (85%). Moreover, comparing with the control, the average number of lung metastatic nodules in tumor-bearing mice reduced 84%, the molecular mechanism of which is related to the down expression of COX-2, matrix metalloproteinase 9 (MMP9) and vascular endothelial growth factor (VEGF). Taken together, our results proved that the developed GTDC@M-R NPs can inhibit the growth and suppress metastasis of TNBC, which broaden our insights into the application of combinational strategy for efficient TNBC therapy. STATEMENT OF SIGNIFICANCE: In this study, we developed a biomimetic nanodelivery system (denoted as GTDC@M-R NPs) based on erythrocyte membrane (M)-camouflaged graphene oxide quantum dots (GOQDs, G) for TNBC therapy. The TAT (T) and RGD (R) peptides were used to endow targeting accumulation ability of Gamabufotalin (CS-6, C) and doxorubicin (DOX, D) in tumor tissue. These GTDC@M-R NPs indicated synergistic chemotherapy against TNBC cells through the precise cell and nuclear targeting, immune escape, and improved DOX sensitivity. A effective inhibition of tumor growth and metastasis was achieved by inhibiting Bcl-2/BAX, COX-2 and VEGF related signal pathways. Our finding suggests that the developed GTDC@M-R NPs present great treating effects in the preclinical models of TNBC, which broaden our insights into the application of combinational strategy for efficient TNBC therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Due to the non-targeted release of anti-cancer agent gamabufotalin (CS-6), conventional chemotherapy using this drug can cause serious side effects, which accordingly result in poor therapeutic efficiency. Recently, the development of smart nanodrug systems has attracted more and more attention due to their significant advantages of high loading efficiency, controllable release behavior and targeted accumulation at tumor sites. In this study, a nanodrug system named as HA@RBC@PB@CS-6 NPs (HRPC) was constructed. In this system, Prussian blue nanoparticles (PB NPs) with hollow porous structure were used as the carrier for CS-6 and photothermal sensitizer simultaneously. The result indicated that the encapsulation of erythrocyte membrane on the PB NPs prolonged the blood circulation life to 10 h and improved the immune evasion ability for more than 60%, as well, which is beneficial for the targeting molecule (HA) to achieve high concentration accumulation of HRPCs at tumor sites. Moreover, we also disclosed that loading drug of CS-6 performed its ultra-strong anti-tumor function partly through markedly suppressing the expression of HSP70, which conversely amplified the efficiency of photothermal therapy. The in vivo study demonstrated the outstanding performance of HRPC in synergistic photothermal/chemotherapy of cancer without side effect to normal tissues., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Modified magnetic starch nanoparticles (FA-StNP@Fe2O3) were synthesized by conjugating folic acid (FA-PEG-NH2) onto the surface of magnetic starch nanoparticles (StNP@Fe2O3) prepared by reverse microemulsion method. The synthesized FA-StNP@Fe2O3 was investigated by transmission electron microscopy and zeta potential analysis. The average size of its well dispersed particles was 250 nm. The iron concentration of 2 mg/g was detected by phenanthroline method. Placing FA-StNP@Fe2O3 nanoparticles in the alternating magnetic field for 30 min resulted in an increase in the suspension temperature from ambient temperature (37°) to a value between 42° and 43°. Co-cultured nanoparticles and Hela cell line or normal HUEC-12 cell line, and the biological effects at the cellular level were investigated in the alternating magnetic field using MTT assay, Hochest-PI double staining and flow cytometry analysis. Experimental results showed that FA-StNP@Fe2O3 within acertain concentration range has no obvious effect on cell proliferation. When treated in the magnetic field, apoptosis rate on Hela induced by FA-StNP@Fe2O3 was 13.4%. Prussian blue staining analysis confirmed that the nanoparticles modified with folic acid had improved ability in tumor cell-targeting, and therefore, potential applications in biomedical and magnetocaloric areas. It is expected be applied in tumor targeting therapy in the near future. [ABSTRACT FROM AUTHOR]

Dialdehyde starch nanoparticles (DASNP) were prepared by the redox reaction of NaIO4 and starch in water-in-oil microemulsion. IR spectrum showed that DASNP had aldehyde groups, and quantitative alkali consumption showed that its dialdehyde content was about (50±5)%. The average diameter of DASNP determined by SEM was about 100 nm. TGA-DTA showed that its thermal stability was better than starch nanoparticle (StNP) and dialdehyde starch (DAS). Its low biological toxicity was detected by cell experiment. Also the best mass ratio of doxorubicin (DOX) to combined DASNP detected by UV-VIS was 15 : 1, and the product was effective for controlled release of DOX. The cell experiment showed that the drug-carrier particle (DOX-DASNP) can release DOX for a long time and strengthened the effect of the anticancer drug. This work demonstrates that the DASNP, which has good thermal stability, small particle size, low biological toxicity, and slowly anticancer drug-releasing to strengthen drug effect, is a potentially useful carrier for anticancer drug. [ABSTRACT FROM AUTHOR]

Anion starch nanoparticles (StNP) were prepared in water-in-oil microemulsion. Folate modified with PEG was conjugated to the surface of StNP to obtain the folate-conjugated starch nanoparticles (FA-PEG/StNP). The average diameter of FA-PEG/StNP determined by AFM and Zeta-Sizer apparatus was about 130 nm. Doxorubicin (DOX)-loaded FA-PEG/StNP was obtained via infiltrating combination. The result of UV spectrophotometer showed that the saturation concentration of DOX-loaded FA-PEG/StNP was 28 µg/mg, which was effective for the controlled release of anticancer drug DOX. The cell experiments showed that the Lc50 of DOX-loaded FA-PEG/StNP and DOX-loaded StNP was higher than that of DOX, which indicates that FA-PEG/StNP and StNP can decrease the toxicity of DOX; while the lethal rate of DOX-loaded FA-PEG/StNP was 3 times that of DOX-loaded StNP with the same quantity of DOX, which indicates that FA in FA-PEG/StNP is effective for improving the targeting function of nanoparticles, thus enhancing the inhibition effect of anticancer drug to cancer cell. This work demonstrates that the FA-PEG/StNP system is a potentially useful system for the targeted delivery of anticancer drug DOX. [ABSTRACT FROM AUTHOR]