scholarly journals Indocyanine Green-Nexturastat A-PLGA Nanoparticles Combine Photothermal and Epigenetic Therapy for Melanoma

Nanomaterials ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 161 ◽  
Author(s):  
Debbie K. Ledezma ◽  
Preethi B. Balakrishnan ◽  
Juliana Cano-Mejia ◽  
Elizabeth E. Sweeney ◽  
Melissa Hadley ◽  
...  
Keyword(s):  
Indocyanine Green ◽  
Near Infrared ◽  
Specific Activity ◽  
Melanoma Cells ◽  
Plga Nanoparticles ◽  
Epigenetic Therapy ◽  
Photothermal Heating ◽  
Epigenetic Drug

In this study, we describe poly (lactic-co-glycolic) acid (PLGA)-based nanoparticles that combine photothermal therapy (PTT) with epigenetic therapy for melanoma. Specifically, we co-encapsulated indocyanine green (ICG), a PTT agent, and Nexturastat A (NextA), an epigenetic drug within PLGA nanoparticles (ICG-NextA-PLGA; INAPs). We hypothesized that combining PTT with epigenetic therapy elicits favorable cytotoxic and immunomodulatory responses that result in improved survival in melanoma-bearing mice. We utilized a nanoemulsion synthesis scheme to co-encapsulate ICG and NextA within stable and monodispersed INAPs. The INAPs exhibited concentration-dependent and near-infrared (NIR) laser power-dependent photothermal heating characteristics, and functioned as effective single-use agents for PTT of melanoma cells in vitro. The INAPs functioned as effective epigenetic therapy agents by inhibiting the expression of pan-histone deacetylase (HDAC) and HDAC6-specific activity in melanoma cells in vitro. When used for both PTT and epigenetic therapy in vitro, the INAPs increased the expression of co-stimulatory molecules and major histocompatibility complex (MHC) Class I in melanoma cells relative to controls. These advantages persisted in vivo in a syngeneic murine model of melanoma, where the combination therapy slowed tumor progression and improved median survival. These findings demonstrate the potential of INAPs as agents of PTT and epigenetic therapy for melanoma.

scholarly journals Aloe derived nanovesicle as a functional carrier for indocyanine green encapsulation and phototherapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lupeng Zeng ◽  
Huaying Wang ◽  
Wanhua Shi ◽  
Lingfan Chen ◽  
Tingting Chen ◽  
...  
Keyword(s):  
Indocyanine Green ◽  
Retention Rate ◽  
Drug Carrier ◽  
Heating System ◽  
Melanoma Cells ◽  
Transdermal Administration ◽  
Promising Perspective ◽  
And Storage

Abstract Background Cancer is one of the devastating diseases in the world. The development of nanocarrier provides a promising perspective for improving cancer therapeutic efficacy. However, the issues with potential toxicity, quantity production, and excessive costs limit their further applications in clinical practice. Results Herein, we proposed a nanocarrier obtained from aloe with stability and leak-proofness. We isolated nanovesicles from the gel and rind of aloe (gADNVs and rADNVs) with higher quality and yield by controlling the final centrifugation time within 20 min, and modulating the viscosity at 2.98 mPa S and 1.57 mPa S respectively. The gADNVs showed great structure and storage stability, antioxidant and antidetergent capacity. They could be efficiently taken up by melanoma cells, and with no toxicity in vitro or in vivo. Indocyanine green (ICG) loaded in gADNVs (ICG/gADNVs) showed great stability in both heating system and in serum, and its retention rate exceeded 90% after 30 days stored in gADNVs. ICG/gADNVs stored 30 days could still effectively damage melanoma cells and inhibit melanoma growth, outperforming free ICG and ICG liposomes. Interestingly, gADNVs showed prominent penetrability to mice skin which might be beneficial to noninvasive transdermal administration. Conclusions Our research was designed to simplify the preparation of drug carrier, and reduce production cost, which provided an alternative for the development of economic and safe drug delivery system. Graphical Abstract

scholarly journals Homologous and Mitochondrial Targeting Synergistic Induction of Apoptosis and Ferroptosis Enhanced PDT Performance Against Osteosarcoma HOS

2021 ◽  
Author(s):  
Yang Wang ◽  
Liang Zhang ◽  
Guosheng Zhao ◽  
Yuan Zhang ◽  
Fangbiao Zhan ◽  
...  
Keyword(s):  
Cell Line ◽  
Molecular Mechanisms ◽  
Near Infrared ◽  
Inhibitory Effect ◽  
Plga Nanoparticles ◽  
Mitochondrial Targeting ◽  
Dual Targeting ◽  
Poly Ethylene

Abstract Background: There have been no prominent advancements in osteosarcoma (OS) treatment in the past 20 years. Although photodynamic therapy (PDT) is an emerging technique for cancer therapy, its lack of targeting in OS treatment severely limits its applications.Methods: In this study, we constructed a potential theranostic nanoplatform by using (poly (ethylene glycol) polylactic-co-Glycolic acid (PEG-PLGA) nanoparticles (NPs) wrapping IR780 into the core (PEG-PLGA-IR780 NPs), which was further camouflaged with human OS cell membranes from the HOS cell line (MH-PEG-PLGA-IR780 NPs) to show homologous and mitochondrial targeting capacities. In addition, the potential underlying anticancer mechanisms of MH-PEG-PLGA-IR780 NPs-mediated PDT was investigated.Results: We demonstrated that the MH-PEG-PLGA-IR780 NPs had excellent tumor/mitochondrial targeting with the help of homologous targeting to HOS cell line. Moreover, the excellent photoacoustic (PA)/fluorescence (FL) imaging ability of MH-PEG-PLGA-IR780 NPs laid a foundation for further applications. Under near-infrared (NIR) irradiation, we demonstrated that dual-targeting NPs-mediated PDT could significantly induce HOS cell apoptosis and ferroptosis, and further explored apoptosis was triggered by cytochrome c-activated mitochondrial apoptosis (endogenous apoptosis), and the specific molecular mechanisms of ferroptosis is the activation of NCOA4-mediated ferritinophagy and the passivation of GPX4 in vitro, synergistically leading to the excessive accumulation of ROS. In addition, MH-PEG-PLGA-IR780 NPs-induced PDT also showed an obvious inhibitory effect on tumor growth in vivo. Conclusion: These results suggest the dual-targeting-based theranostic nanoplatform provides an effective method to improve PDT performance in OS and paves a new and promising way for OS therapy.

scholarly journals Comparative Study of the Optical and Heat Generation Properties of IR820 and Indocyanine Green

2012 ◽  
Vol 11 (2) ◽  
pp. 7290.2011.00031 ◽  
Author(s):  
Alicia Fernandez-Fernandez ◽  
Romila Manchanda ◽  
Tingjun Lei ◽  
Denny A. Carvajal ◽  
Yuan Tang ◽  
...  
Keyword(s):  
Indocyanine Green ◽  
Near Infrared ◽  
Experimental Models ◽  
Cyanine Dye ◽  
Laser Exposure ◽  
Fluorescence Signal ◽  
Thermal Generation ◽  
Significant Difference

Near-infrared (NIR) fluorophores are the focus of extensive research for combined molecular imaging and hyperthermia. In this study, we showed that the cyanine dye IR820 has optical and thermal generation properties similar to those of indocyanine green (ICG) but with improved in vitro and in vivo stability. The fluorescent emission of IR820 has a lower quantum yield than ICG but less dependence of the emission peak location on concentration. IR820 demonstrated degradation half-times approximately double those of ICG under all temperature and light conditions in aqueous solution. In hyperthermia applications, IR820 generated lower peak temperatures than ICG (4–9%) after 3-minute laser exposure. However, there was no significant difference in hyperthermia cytotoxicity, with both dyes causing significant cell growth inhibition at concentrations ≥ 5 μM. Fluorescent images of cells with 10 μM IR820 were similar to ICG images. In rats, IR820 resulted in a significantly more intense fluorescence signal and significantly higher organ dye content than for ICG 24 hours after intravenous dye administration ( p < .05). Our study shows that IR820 is a feasible agent in experimental models of imaging and hyperthermia and could be an alternative to ICG when greater stability, longer image collection times, or more predictable peak locations are desirable.

scholarly journals Liposome-Templated Indocyanine Green J- Aggregates for In Vivo Near Infrared Imaging and Stable Photothermal Heating

2020 ◽  
Vol 4 (2) ◽  
pp. 91-106 ◽  
Author(s):  
Calvin C. L. Cheung ◽  
Guanglong Ma ◽  
Kostas Karatasos ◽  
Jani Seitsonen ◽  
Janne Ruokolainen ◽  
...  
Keyword(s):  
Indocyanine Green ◽  
Near Infrared ◽  
Infrared Imaging ◽  
Near Infrared Imaging ◽  
Photothermal Heating ◽  
J Aggregates

scholarly journals Novel Rifampicin and Indocyanine Green Co-Loaded Perfluorocarbon Nanodroplets Provide Effective In Vivo Photo–Chemo–Probiotic Antimicrobility against Pathogen of Acne Vulgaris Cutibacterium acnes

Nanomaterials ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 1095
Author(s):  
Kuang-Hung Hsiao ◽  
Chun-Ming Huang ◽  
Yu-Hsiang Lee
Keyword(s):  
Indocyanine Green ◽  
Staphylococcus Epidermidis ◽  
Near Infrared ◽  
Acne Vulgaris ◽  
Inhibition Zone ◽  
Inflammatory Protein ◽  
Cutibacterium Acnes ◽  
Macrophage Inflammatory Protein

Acne vulgaris is one of the most prevalent dermatological diseases among adolescents and is often associated with overgrowth of Cutibacterium acnes (C. acnes) in the pilosebaceous units. In this study, we aimed to develop novel rifampicin (RIF) and indocyanine green (ICG) co-loaded perfluorocarbon nanodroplets named RIPNDs which can simultaneously provide photo-, chemo-, and probiotic-antimicrobility, and explore their efficacy in treatment of C. acnes in vitro and in vivo. The RIPNDs were first characterized as being spherical in shape, with a size of 238.6 ± 7.51 nm and surface charge of −22.3 ± 3.5 mV. Then, the optimal dosages of Staphylococcus epidermidis–produced fermentation product medium (FPM) and RIPND were determined as 25% (v/v) and [RIF]/[ICG] = 3.8/20 μM, respectively, based on the analyses of inhibition zone and cytotoxicity in vitro. Through the in vivo study using C. acnes–inoculated mice, our data showed that the group treated with FPM followed by RIPNDs + near infrared (NIR) irradiation obtained the least granulocytes/macrophage-inflammatory protein 2 expression level in the epidermis, and showed a significantly lower microbial colony population compared to the groups treated with equal amount of RIF, FPM, RIPNDs, and/or combination of the above ± NIR. These results indicated that the RIPND-mediated photo–chemo–probiotic therapeutics was indeed able to rapidly suppress inflammatory response of the skin and provide a robust antibacterial effect against C. acnes with limited use of antibiotics. Taken altogether, we anticipate that the RIPND is highly potential for use in the clinical treatment of acne vulgaris.

scholarly journals Dual-colour (near-infrared/visible) emitting annexin V for fluorescence imaging of tumour cell apoptosis in vitro and in vivo

RSC Advances ◽  
2020 ◽  
Vol 10 (63) ◽  
pp. 38244-38250
Author(s):  
Setsuko Tsuboi ◽  
Takashi Jin
Keyword(s):  
Tumor Cell ◽  
Indocyanine Green ◽  
Fluorescence Imaging ◽  
Cell Apoptosis ◽  
Near Infrared ◽  
Annexin V ◽  
Tumor Cell Apoptosis ◽  
Dual Colour

Indocyanine green labeled recombinant annexin V probes (ICG–EGFP–Annexin V and ICG–mPlum–Annexin V) were synthesized for near-infrared and visible fluorescence imaging of tumor cell apoptosis both in vitro and in vivo.

Ancylostoma caninum Anticoagulant Peptide Blocks Metastasis In Vivo and Inhibits Factor Xa Binding to Melanoma Cells In Vitro

1998 ◽  
Vol 79 (05) ◽  
pp. 1041-1047 ◽  
Author(s):  
Kathleen M. Donnelly ◽  
Michael E. Bromberg ◽  
Aaron Milstone ◽  
Jennifer Madison McNiff ◽  
Gordon Terwilliger ◽  
...  
Keyword(s):  
Active Site ◽  
Thrombin Generation ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Melanoma Cells ◽  
Factor V ◽  
Ancylostoma Caninum ◽  
Metastatic Activity

SummaryWe evaluated the in vivo anti-metastatic activity of recombinant Ancylostoma caninum Anticoagulant Peptide (rAcAP), a potent (Ki = 265 pM) and specific active site inhibitor of human coagulation factor Xa originally isolated from bloodfeeding hookworms. Subcutaneous injection of SCID mice with rAcAP (0.01-0.2 mg/mouse) prior to tail vein injection of LOX human melanoma cells resulted in a dose dependent reduction in pulmonary metastases. In order to elucidate potential mechanisms of rAcAP’s anti-metastatic activity, experiments were carried out to identify specific interactions between factor Xa and LOX. Binding of biotinylated factor Xa to LOX monolayers was both specific and saturable (Kd = 15 nM). Competition experiments using antibodies to previously identified factor Xa binding proteins, including factor V/Va, effector cell protease receptor-1, and tissue factor pathway inhibitor failed to implicate any of these molecules as significant binding sites for Factor Xa. Functional prothrombinase activity was also supported by LOX, with a half maximal rate of thrombin generation detected at a factor Xa concentration of 2.4 nM. Additional competition experiments using an excess of either rAcAP or active site blocked factor Xa (EGR-Xa) revealed that most of the total factor Xa binding to LOX is mediated via interaction with the enzyme’s active site, predicting that the vast majority of cell-associated factor Xa does not participate directly in thrombin generation. In addition to establishing two distinct mechanisms of factor Xa binding to melanoma, these data raise the possibility that rAcAP’s antimetastatic effect in vivo might involve novel non-coagulant pathways, perhaps via inhibition of active-site mediated interactions between factor Xa and tumor cells.

Soluble Thrombomodulin Purified from Human Urine Exhibits a Potent Anticoagulant Effect In Vitro and In Vivo

1995 ◽  
Vol 73 (05) ◽  
pp. 805-811 ◽  
Author(s):  
Yasuo Takahashi ◽  
Yoshitaka Hosaka ◽  
Hiromi Niina ◽  
Katsuaki Nagasawa ◽  
Masaaki Naotsuka ◽  
...  
Keyword(s):  
Human Urine ◽  
Specific Activity ◽  
Anticoagulant Activity ◽  
Rabbit Lung ◽  
Soluble Thrombomodulin ◽  
Molecular Weights ◽  
Dose Dependent Fashion ◽  
Dose Dependent

SummaryWe examined the anticoagulant activity of two major molecules of soluble thrombomodulin purified from human urine. The apparent molecular weights of these urinary thrombomodulins (UTMs) were 72,000 and 79,000, respectively. Both UTMs showed more potent cofactor activity for protein C activation [specific activity >5,000 thrombomodulin units (TMU)/mg] than human placental thrombomodulin (2,180 TMU/mg) and rabbit lung thrombomodulin (1,980 TMU/mg). The UTMs prolonged thrombin-induced fibrinogen clotting time (>1 TMU/ml), APTT (>5 TMU/ml), TT (>5 TMU/ml) and PT (>40 TMU/ml) in a dose-dependent fashion. These effects appeared in the concentration range of soluble thrombomodulins present in human plasma and urine. In the rat DIC model induced by thromboplastin, administration of UTMs by infusion (300-3,000 TMU/kg) restored the hematological abnormalities derived from DIC in a dose-dependent fashion. These results demonstrate that UTMs exhibit potent anticoagulant and antithrombotic activities, and could play a physiologically important role in microcirculation.

Effects of Heparin Oligosaccharides with High Affinity for Antithrombin III in Experimental Venous Thrombosis

1982 ◽  
Vol 47 (03) ◽  
pp. 244-248 ◽  
Author(s):  
D P Thomas ◽  
Rosemary E Merton ◽  
T W Barrowcliffe ◽  
L Thunberg ◽  
U Lindahl
Keyword(s):  
Antithrombin Iii ◽  
Specific Activity ◽  
High Specific Activity ◽  
Factor Xa ◽  
Blood Levels ◽  
Thrombin Time ◽  
High Affinity ◽  
Very High

SummaryThe in vitro and in vivo characteristics of two oligosaccharide heparin fragments have been compared to those of unfractionated mucosal heparin. A decasaccharide fragment had essentially no activity by APTT or calcium thrombin time assays in vitro, but possessed very high specific activity by anti-Factor Xa assays. When injected into rabbits at doses of up to 80 ¼g/kg, this fragment was relatively ineffective in impairing stasis thrombosis despite producing high blood levels by anti-Xa assays. A 16-18 monosaccharide fragment had even higher specific activity (almost 2000 iu/mg) by chromogenic substrate anti-Xa assay, with minimal activity by APTT. When injected in vivo, this fragment gave low blood levels by APTT, very high anti-Xa levels, and was more effective in preventing thrombosis than the decasaccharide fragment. However, in comparison with unfractionated heparin, the 16-18 monosaccharide fragment was only partially effective in preventing thrombosis, despite producing much higher blood levels by anti-Xa assays.It is concluded that the high-affinity binding of a heparin fragment to antithrombin III does not by itself impair venous thrombogenesis, and that the anti-Factor Xa activity of heparin is only a partial expression of its therapeutic potential.

scholarly journals Development of a Topical Insulin Polymeric Nanoformulation for Skin Burn Regeneration: An Experimental Approach

2021 ◽  
Vol 22 (8) ◽  
pp. 4087
Author(s):  
Maria Quitério ◽  
Sandra Simões ◽  
Andreia Ascenso ◽  
Manuela Carvalheiro ◽  
Ana Paula Leandro ◽  
...  
Keyword(s):  
Wound Healing ◽  
Healing Process ◽  
In Vitro Release ◽  
Peptide Hormone ◽  
Plga Nanoparticles ◽  
Wound Healing Process ◽  
Target Area ◽  
Encapsulation Process

Insulin is a peptide hormone with many physiological functions, besides its use in diabetes treatment. An important role of insulin is related to the wound healing process—however, insulin itself is too sensitive to the external environment requiring the protective of a nanocarrier. Polymer-based nanoparticles can protect, deliver, and retain the protein in the target area. This study aims to produce and characterize a topical treatment for wound healing consisting of insulin-loaded poly-DL-lactide/glycolide (PLGA) nanoparticles. Insulin-loaded nanoparticles present a mean size of approximately 500 nm and neutral surface charge. Spherical shaped nanoparticles are observed by scanning electron microscopy and confirmed by atomic force microscopy. SDS-PAGE and circular dichroism analysis demonstrated that insulin preserved its integrity and secondary structure after the encapsulation process. In vitro release studies suggested a controlled release profile. Safety of the formulation was confirmed using cell lines, and cell viability was concentration and time-dependent. Preliminary safety in vivo assays also revealed promising results.

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