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Due to the non-targeted release and low solubility of anti-gastric cancer agent, apatinib (Apa), a first-line drug with long-term usage in a high dosage often induces multi-drug resistance and causes serious side effects. In order to avoid these drawbacks, lipid-film-coated Prussian blue nanoparticles (PB NPs) with hyaluronan (HA) modification was used for Apa loading to improve its solubility and targeting ability. Furthermore, anti-tumor compound of gamabufotalin (CS-6) was selected as a partner of Apa with reducing dosage for combinational gastric therapy. Thus, HA-Apa-Lip@PB-CS-6 NPs were constructed to synchronously transport the two drugs into tumor tissue. In vitro assay indicated that HA-Apa-Lip@PB-CS-6 NPs can synergistically inhibit proliferation and invasion/metastasis of BGC-823 cells via downregulating vascular endothelial growth factor receptor (VEGFR) and matrix metalloproteinase-9 (MMP-9). In vivo assay demonstrated strongest anti-tumor growth and liver metastasis of HA-Apa-Lip@PB-CS-6 NPs administration in BGC-823 cells-bearing mice compared with other groups due to the excellent penetration in tumor tissues and outstanding synergistic effects. In summary, we have successfully developed a new nanocomplexes for synchronous Apa/CS-6 delivery and synergistic gastric cancer (GC) therapy.
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Over-expression of glutathione S-transferase (GST) can promote Cisplatin resistance in hepatocellular carcinoma (HCC) treatment. Hence, inhibiting GST is an attractive strategy to improve Cisplatin sensitivity in HCC therapy. Although several synthesized GST inhibitors have been developed, the side effects and narrow spectrum for anticancer seriously limit their clinical application. Considering the abundance of natural compounds with anticancer activity, this study developed a rapid fluorescence technique to screen "green" natural GST inhibitors with high specificity. The fluorescence assay demonstrated that schisanlactone B (hereafter abbreviated as C1) isolated from Xue tong significantly down-regulated GST levels in Cisplatin-resistant HCC cells in vitro and in vivo. Importantly, C1 can selectively kill HCC cells from normal liver cells, effectively improving the therapeutic effect of Cisplatin on HCC mice by down-regulating GST expression. Considering the high GST levels in HCC patients, this compound demonstrated the high potential for sensitizing HCC therapy in clinical practice by down-regulating GST levels.
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Necroptotic immunogenic cell death (ICD) can activate the human immune system to treat the metastasis and recurrence of triple-negative breast cancer (TNBC). However, developing the necroptotic inducer and precisely delivering it to the tumor site is the key issue. Herein, we reported that the combination of shikonin (SHK) and chitosan silver nanoparticles (Chi-Ag NPs) effectively induced ICD by triggering necroptosis in 4T1 cells. Moreover, to address the lack of selectivity of drugs for in vivo application, we developed an MUC1 aptamer-targeted nanocomplex (MUC1@Chi-Ag@CPB@SHK, abbreviated as MUC1@ACS) for co-delivering SHK and Chi-Ag NPs. The accumulation of MUC1@ACS NPs at the tumor site showed a 6.02-fold increase compared to the free drug. Subsequently, upon reaching the tumor site, the acid-responsive release of SHK and Chi-Ag NPs from MUC1@ACS NPs cooperatively induced necroptosis in tumor cells by upregulating the expression of RIPK3, p-RIPK3, and tetrameric MLKL, thereby effectively triggering ICD. The sequential maturation of dendritic cells (DCs) subsequently enhanced the infiltration of CD8+ and CD4+ T cells in tumors, while inhibiting regulatory T cells (Treg cells), resulting in the effective treatment of primary and distal tumor growth and the inhibition of TNBC metastasis. This work highlights the importance of nanoparticles in mediating drug interactions during necroptotic ICD.
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Quitosano , Nanopartículas del Metal , Naftoquinonas , Necroptosis , Proteína Serina-Treonina Quinasas de Interacción con Receptores , Plata , Neoplasias de la Mama Triple Negativas , Naftoquinonas/farmacología , Naftoquinonas/química , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Quitosano/química , Plata/química , Plata/farmacología , Animales , Nanopartículas del Metal/química , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Línea Celular Tumoral , Femenino , Necroptosis/efectos de los fármacos , Humanos , Ratones , Muerte Celular Inmunogénica/efectos de los fármacos , Ratones Endogámicos BALB C , Mucina-1/metabolismo , Sinergismo Farmacológico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/químicaRESUMEN
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.
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Hipertermia Inducida , Nanopartículas , Neoplasias de la Mama Triple Negativas , Humanos , Fototerapia , Neoplasias de la Mama Triple Negativas/terapia , Neoplasias de la Mama Triple Negativas/patología , Biomimética , Muerte Celular Inmunogénica , Nanopartículas/uso terapéutico , Línea Celular TumoralRESUMEN
Although carbon monoxide (CO)-based treatments have demonstrated the high cancer efficacy by promoting mitochondrial damage and core-region penetrating ability, the efficiency was often compromised by protective autophagy (mitophagy). Herein, cannabidiol (CBD) is integrated into biomimetic carbon monoxide nanocomplexes (HMPOC@M) to address this issue by inducing excessive autophagy. The biomimetic membrane not only prevents premature drugs leakage, but also prolongs blood circulation for tumor enrichment. After entering the acidic tumor microenvironment, carbon monoxide (CO) donors are stimulated by hydrogen oxide (H2O2) to disintegrate into CO and Mn2+. The comprehensive effect of CO/Mn2+ and CBD can induce ROS-mediated cell apoptosis. In addition, HMPOC@M-mediated excessive autophagy can promote cancer cell death by increasing autophagic flux via class III PI3K/BECN1 complex activation and blocking autolysosome degradation via LAMP1 downregulation. Furthermore, in vivo experiments showed that HMPOC@M+ laser strongly inhibited tumor growth and attenuated liver and lung metastases by downregulating VEGF and MMP9 proteins. This strategy may highlight the pro-death role of excessive autophagy in TNBC treatment, providing a novel yet versatile avenue to enhance the efficacy of CO treatments. Importantly, this work also indicated the applicability of CBD for triple-negative breast cancer (TNBC) therapy through excessive autophagy.
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Acute kidney injury (AKI) is a common clinical syndrome with limited treatment options and high mortality rates. Proximal tubular epithelial cells (PTECs) play a key role in AKI progression. Subcellular dysfunctions, including mitochondrial, nuclear, endoplasmic reticulum and lysosomal dysfunctions, are extensively studied in PTECs. These studies have led to the development of potential therapeutic drugs. However, clinical development of those drugs faces challenges such as low solubility, short circulation time and severe systemic side effects. Nanotechnology provides a promising solution by improving drug properties through nanocrystallization and enabling targeted delivery to specific sites. This review summarizes advancements and limitations of nanoparticle-based drug-delivery systems in targeting PTECs and subcellular organelles, particularly mitochondria, for AKI treatment.
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Lesión Renal Aguda , Nanopartículas , Humanos , Preparaciones Farmacéuticas/metabolismo , Túbulos Renales Proximales/metabolismo , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/metabolismo , Mitocondrias , Células Epiteliales , Nanopartículas/uso terapéutico , RiñónRESUMEN
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 H2O2 in the bacterial microenvironment to upregulate the O2 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.
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Diabetes Mellitus , Staphylococcus aureus Resistente a Meticilina , Nanopartículas , Fotoquimioterapia , Porfirinas , Animales , Ratones , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Fotoquimioterapia/métodos , Peróxido de Hidrógeno/farmacología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacterias , Porfirinas/uso terapéutico , Porfirinas/farmacología , Línea Celular TumoralRESUMEN
Although combined photodynamic/photothermal therapy (PDT/PTT) has been used for cancer theranostics recently, their therapeutic efficacy has been compromised by the low O2 partial pressure and high concentration of GSH in the tumor microenvironment (TME). Thus, the construction of intelligent TME-responsive nanocomplexes is a powerful strategy for addressing the above issues. In this study, MnO2-coated Prussian blue nanocomplexes (PM NPs) were designed as O2 suppliers and GSH depletion agents to reprogram the TME. Subsequently, tumor-targeting peptide (RGD)-modified erythrocyte membrane vesicles loaded with photosensitizer (Ce6) were used to camouflage PM NPs (PMRCR NPs). Importantly, the prepared PMRCR NPs exhibited excellent photothermal performance with a photothermal conversion efficiency of 44.9%. Moreover, the in vitro PDT/PTT was enhanced, by which the cell viability was reduced to 21.4%, which is lower than the 55.6% (PDT) and 66.7% (PTT) of PMRCR NPs with a single laser treatment. By modeling 4T1 tumor-bearing mice, the combined PDT/PTT of PMRCR NPs greatly inhibited tumor growth, and after 20 days, a tumor inhibition rate of 92.9% was achieved. This work provides a promising strategy by developing TME-reprogrammed multifunctional nanocomplexes to enhance PDT/PTT antitumor efficacy.
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Fotoquimioterapia , Neoplasias de la Mama Triple Negativas , Humanos , Animales , Ratones , Membrana Eritrocítica , Compuestos de Manganeso , Óxidos , Microambiente TumoralRESUMEN
Direct use of chemotherapy drugs in the treatment of gastric cancer often leads to systemic side effects and unsatisfied therapeutic efficacy due to the lack of tumour-targeting ability. The excellent properties of nanoparticles make them good tools to provide more options for the targeted delivery of chemotherapeutic drugs. Herein, we developed a novel nanomedicine (GOQD-ICG-CS-6@HM nanoparticles, GIC@HM NPs), which employed graphene oxide quantum dots (GOQDs) to co-load photosensitizer indocyanine green (ICG) and chemotherapeutic drug gamabufotalin (CS-6) as the core and wrapped with the hybrid membrane (erythrocyte membrane and gastric cancer cell membrane, HM) on its surface. This nanomedicine possesses the functions of photothermal therapy and chemotherapy, making it a good choice for the treatment of gastric cancer. The results showed that the bionic-coated hybrid membrane not only improves the biocompatibility of the nanomedicine, and prolong its circulating half-life, but also delivers the drug to the tumour site precisely and improves the efficiency of drug utilisation. In vitro and in vivo studies further showed that GIC@HM NPs exhibited combinational effects on tumour therapy while displaying no obvious side effects on normal tissue. To sum up, the newly developed GIC@HM NPs provide a safer, more efficient, and more precise method for gastric cancer treatment.
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Nanopartículas , Puntos Cuánticos , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Biomimética , Fototerapia/métodos , Verde de Indocianina , Membrana Eritrocítica , Línea Celular TumoralRESUMEN
As one kind of aggressive cancer, triple-negative breast cancer (TNBC) has become one of the major causes of women mortality worldwide. Recently, combinational chemo-PDT therapy based on nanomaterials has been adopted for the treatment of malignant tumor. However, the efficacy of PDT was partly compromised under tumor hypoxia environment due to the lack of sustainable O2 supply. In this study, CeO2-loaded nanoparticles (CeNPs) with peroxidase activity were synthesized to autonomously generate O2 by decomposing H2O2 within tumor region and reprogramming the hypoxia microenvironment as well. Meanwhile, the compound cinobufagin (CS-1) was loaded for inhibiting TNBC growth and metastasis. Moreover, the hybrid membrane camouflage was adopted to improve the biocompatibility and targeting ability of nanocomplexes. In vitro assay demonstrated that decomposition of H2O2 by CeO2 achieved sustainable O2 supply, which accordingly improved the efficacy of PDT. In turn, the generated O2 improved the cytotoxicity and anti-tumor migration effect of CS-1 by downregulating HIF-1α and MMP-9 levels. In vivo assay demonstrated that the combination of CS-1 and PDT significantly inhibited the growth and distance metastasis of tumor in MDA-MB-231 bearing mice. Thus, this chemo-PDT strategy achieved satisfactory therapeutic effects by smartly utilizing the enzyme activity of nanodrugs and special micro-environment of tumor.
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Nanopartículas , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Ratones , Animales , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Peróxido de Hidrógeno , Línea Celular Tumoral , Microambiente TumoralRESUMEN
Klebsiella pneumoniae (K. pneumoniae) is a common bacterium whose drug-resistant can cause surgical failures and incurable infections in hospital patients. Thus, how to reverse or delay the resistance induction has become a great challenge for development antiresistant drug. Recently, the combination of nanomaterial-loaded antibiotics with photothermal therapy showed the efficient antibacteria ability under a low dosage of antibiotics. In this study, a nanocomposite of HMPB NPs with inherent photothermal therapy capability was used to eradicate K. pneumoniae after loading with Ofloxacin, an antibiotic against K. pneumoniae in vitro and in vivo. The nanocomplexes named as Ofloxacin@HMPB@HA NPs showed a higher effect against K. pneumoniae by destroying cell integrity and inducing ATP leakage with the assistance of laser irradiation, compared with sole Ofloxacin@HMPB@HA NPs or laser irradiation. Surgical wound infection assay further demonstrated the efficient killing K. pneumoniae and promoting the formation of new tissues, as well, which was reflected by the rapid healing of surgical wound. In summary, these results indicate the great potential of this combinational tactic based on Ofloxacin@HMPB@HA NPs for preventing the failure caused by K. pneumoniae infection.
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Infecciones por Klebsiella , Herida Quirúrgica , Antibacterianos/farmacología , Humanos , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae , Ofloxacino/farmacología , Ofloxacino/uso terapéutico , Herida Quirúrgica/tratamiento farmacológicoRESUMEN
The development of new reagents combining with nanotechnology has become an efficient strategy for improving the immune escaping ability and increasing local drug concentration for natural compounds with low therapy efficiency. In this study, we prepared biomimetic membrane-coated Prussian blue nanoparticles (PB NPs) for the treatment of atherosclerosis, using the function of Artemisinin (ART) and Procyanidins (PC) on the lipid influx and cholesterol efflux of macrophages, two logical steps involved in the plaque progression. In vitro results indicated that the prepared nanocomplexes have significant scavenging effect on ROS and NO, followed by inhibiting NF-κB/NLRP3 pathway, leading to the suppression of lipid influx. Meanwhile, they can notably reduce the uptake and internalization of oxLDL through significantly enhancing AMPK/mTOR/autophagy pathway, accompanied by promoting cholesterol efflux. In vivo study showed that the improved biocompatibility and immune-escape ability of nanocomplexes allowed less drug clearance during the circulation and high drug accumulation in the atherosclerotic plaque of ApoE-/- mice model. More importantly, the ART and PC co-loaded nanocomplexes showed the high efficacy against atherosclerosis of ApoE-/- mice model with both 8-week low dosage treatment or 1-week high dosage treatment. These findings indicated that ART and PC co-loaded nanocomplexes was promising for the targeted treatment of atherosclerosis.
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Artemisininas , Aterosclerosis , Placa Aterosclerótica , Proantocianidinas , Animales , Artemisininas/uso terapéutico , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/metabolismo , Colesterol/metabolismo , Ratones , Placa Aterosclerótica/tratamiento farmacológico , Proantocianidinas/uso terapéuticoRESUMEN
Rheumatoid arthritis (RA) is a systemic autoimmune disease underlying a cascade of chronic inflammatory processes. Over the past decades, the response rate of effective RA treatments has remained scarce despite numerous advancements in the current therapeutic interventions, owing largely to the associated off-target adverse events and poor accumulation in the inflamed joints. Recently, there is a high interest in the development of targeted drug delivery system by using nanotechnology, as it can provide a handle to improve the therapy efficacy of RA. Here, multifunctional HA@RFM@PB@SE nanoparticles (HRPS NPs) are developed by loading schisanlactone E (SE, also called with xuetongsu), an anti-RA compound isolated from Tujia ethnomedicine xuetong, into Prussian blue nanoparticles (PB NPs) and further camouflage of RBC-RAFLS hybrid membrane with HA modification onto PB@SE NPs (PS NPs). We demonstrated that the modification of RFM makes PB NPs ideal decoys for targeting inflammatory mediators of arthritis due to the homing effects of the parental cells. Moreover, the encapsulation of RFM on the PB@SE NPs extended the blood circulation time and improved its targeting ability, which accordingly achieved optimal accumulation of SE in arthritic rat paws. In vitro and in vivo assay demonstrated the outstanding performance of HRPS NPs for synergistic chemo-/photothermal therapy of RA without side effects to healthy tissues. Molecular mechanism exploration indicated that the ultrastrong inhibition of synovial hyperplasia and bone destruction was partly via suppressing NF-κB signaling pathway and the expression of matrix metalloproteinases. In summary, the nanodrug delivery system showed controllable release behavior, targeted accumulation at arthritic sites and systemic regulation of immunity, hence improved therapeutic efficacy and clinical outcomes of the disease without attenuating safety.
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Artritis Reumatoide , Nanopartículas , Ratas , Animales , Biomimética , Artritis Reumatoide/tratamiento farmacológico , Fototerapia , Nanopartículas/uso terapéutico , Rayos LáserRESUMEN
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.
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Hipertermia Inducida , Nanopartículas , Neoplasias del Cuello Uterino , Animales , Biomimética , Doxorrubicina , Femenino , Humanos , Indometacina , Ratones , Fototerapia , Terapia Fototérmica , Microambiente Tumoral , Neoplasias del Cuello Uterino/terapiaRESUMEN
In this research, we analyzed the antitumor activity of one new compound Heilaohulignan C (B-6) on the human gastric carcinoma cells. MTT, cell migration, Calcein AM/Propidium Iodide (PI), and flow cytometry in BGC-823 cell line (gastric tumor). Western blot was utilized to distinguish the protein level. Xenografts nude mice were used for in vivo anticancer analysis. H&E staining and laboratory investigation was accomplished for toxicity study. MTT test demonstrated the cytotoxicity of BGC-823 cells, Calcein AM/Propidium Iodide (PI) examine indicated increment dead cells proportion with a high dose of B-6, Flow cytometry (FACS) measure showed that B-6 influenced gastric cancer cells by initiating apoptosis. Western blot analysis confirmed that (B-6) decrease the level of Bcl-2 and increase the level of p53, Bax, and cleaved Caspase-3, this confirms that the B-6 doing the apoptosis through caspase and cytochrome C apoptotic pathways. Also, B-6 particularly decline the tumor volume and tumor size in the xenograft mice. H&E staining additionally supports that B-6 does not have any toxic impact on the normal tissues. This research supports that B-6 have pharmacological activity against gastric cancer, by p53 and mitochondrial dependent apoptotic pathway, and have no toxicity on normal tissues.
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Medicamentos Herbarios Chinos/farmacología , Kadsura , Neoplasias Gástricas , Animales , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Humanos , Kadsura/química , Ratones , Ratones Desnudos , Neoplasias Gástricas/tratamiento farmacológico , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
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.
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Antineoplásicos/farmacología , Liposomas/química , Nanopartículas/química , Transducción de Señal/efectos de los fármacos , Animales , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Materiales Biocompatibles/química , Bufanólidos/química , Bufanólidos/farmacología , Bufanólidos/uso terapéutico , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Humanos , Ratones , Ratones Desnudos , Nanopartículas/metabolismo , Piridinas/química , Piridinas/farmacología , Piridinas/uso terapéutico , Factor de Transcripción STAT3/metabolismo , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Distribución Tisular , Trasplante Heterólogo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
[This corrects the article DOI: 10.1155/2018/3625823.].
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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.
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Contención de Riesgos Biológicos , Nanopartículas , Supervivencia Celular , Ferrocianuros , Nanopartículas/toxicidad , FototerapiaRESUMEN
The side effects of chemical drugs and multi-drug resistance are serious obstacles hindering efficient tumor therapy. Therefore, recently, the combination of chemo/photothermal therapy (CT/PT) has been adopted to address these issues using a low drug dosage. However, the development of multi-functional drug delivery systems with improved immune escape capability and enhanced drug accumulation at specific tumor tissues is still in its infancy. Herein, polyethylene glycol (PEG)-modified WS2 nanosheets (WS2-PEG) were used as a nanocarrier scaffold for doxorubicin (DOX, D) loading and near-infrared fluorescence probe indocyanine green (ICG, I) doping. After surface modification with the erythrocyte membrane (M) and targeted folic acid (FA) molecule, a new biomimetic system (WID@M-FA NPs) with high biocompatibility, prolonged cycle time (3.6-fold longer than WID NPs) and remarkable near-infrared photothermal function was developed for a targeted cervical cancer therapy. The in vitro assay indicated that the photothermal effects caused by ICG upon laser irradiation not only enhanced the cellular uptake of the drug, but also enhanced its tumor cell killing efficiency. Moreover, the targeted accumulation of DOX at the cervical cancer tissue and the synergistic chemo/photothermal therapy finally resulted in tumor elimination to more than 95% without side effects to the normal tissues in vivo. Thus, these excellent preclinical results indicate that WID@M-FA NPs may be an efficient therapeutic modality for the treatment of cervical cancer.
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Hipertermia Inducida , Nanopartículas , Neoplasias del Cuello Uterino , Línea Celular Tumoral , Doxorrubicina/farmacología , Membrana Eritrocítica , Femenino , Humanos , Fototerapia , Terapia Fototérmica , Polietilenglicoles , Neoplasias del Cuello Uterino/terapiaRESUMEN
Due to the significant role of formamidopyrimidine DNA glycosylase (Fpg) in physiological processes and DNA oxidative damage-related diseases, it is essential to establish sensitive methods for monitoring the Fpg activity in vitro and in vivo so as to illustrate its concrete role in these events. In this work, a sensitive, simple and reliable fluorescence assay was developed by taking the advantages of DNAzyme assisted cascade signal amplification and ultra-high fluorescence quenching efficiency of reduced graphene oxide (rGO). This detection system consisted of DNAzyme, rGO and fluorescence probe allows the activity of Fpg to be detected in a linear range from 0 to 80 U/mL with a detection limit of 0.66 U/mL. With the help of this method, 11 natural compounds were screened, and 7 compounds were identified as activators of Fpg. More importantly, the developed assay was used to monitor the activity of Fpg through fluorescence imaging in living Escherichia coli for the first time. The imaging results visually demonstrated the dynamic activation effect of natural compound Ginsenoside Re on the Fpg of Escherichia coli. In summary, these results indicated that this DNAzyme and rGO based fluorescence assay provides a potent strategy for Fpg quantitative assay in vitro and real-time monitoring in living bacteria, which holds great potential for applying on biological study and Fpg-targeted drug screening.