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1.
Anticancer Res ; 40(1): 373-377, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892589

RESUMO

AIM: In colorectal cancer surgery, the efficacy of intestinal blood flow evaluation with the indocyanine green (ICG) fluorescence method using the VISERA ELITE2 system was investigated. PATIENTS AND METHODS: Participants in this study comprised 50 patients who underwent elective laparoscopic colorectal cancer surgery at the Department of Surgery, the Jikei Daisan Hospital. With the ICG fluorescence method, whether it was necessary to change the intestinal transection line for anastomosis was evaluated. RESULTS: For three cases of rectal cancer, the oral transection line determined from macroscopic observation was judged to offer insufficient blood flow according to the ICG fluorescence method. The transection line for anastomosis was changed according to fluorescence. None of these cases showed complications. CONCLUSION: The ICG fluorescence method may allow safe anastomosis in colorectal surgery for cancer.


Assuntos
Cirurgia Colorretal , Verde de Indocianina/química , Laparoscopia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anastomose Cirúrgica , Cirurgia Colorretal/efeitos adversos , Feminino , Fluorescência , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia
2.
BMC Surg ; 19(1): 165, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31699083

RESUMO

BACKGROUND: Pancreatic resection and radiotherapy are powerful tools in the multidisciplinary local treatment of pancreatic ductal adenocarcinoma (PDAC). However, 10-20% of patients with preoperatively resectable PDAC have radiographically occult metastases, which results in laparotomy without resection. This study aims to explore the utility of intraoperative near-infrared (NIR) imaging with indocyanine green (ICG) during staging laparoscopy to detect PDAC metastasis. METHODS: This prospective study will evaluate patients with radiographically non-metastatic PDAC before they undergo planned pancreatic resection or chemoradiotherapy. Enrolled patients will receive ICG intravenously (0.5 mg/kg) before the staging laparoscopy. During the staging laparoscopy, the abdominal cavity will be observed using standard white-light laparoscopic imaging and then using NIR-ICG imaging. Suspicious lesions that are detected using standard imaging and/or NIR-ICG imaging will be examined intraoperatively using frozen sections and permanent specimens. We will evaluate the benefit of NIR-ICG imaging based on its ability to identify additional liver or peritoneal lesions that were not detected during standard white-light imaging. DISCUSSION: This study will help establish the clinical utility of NIR-ICG imaging to more precisely identify metastases from radiographically non-metastatic PDAC. This approach may help avoid needless major surgery or radiotherapy. TRIAL REGISTRATION: This protocol was registered on April 1, 2017 on the UMIN Clinical Trials Registry: UMIN000025900 and February 26, 2019 on the Japan Registry of Clinical Trials: jRCT1051180076.


Assuntos
Carcinoma Ductal Pancreático/diagnóstico por imagem , Verde de Indocianina/química , Laparoscopia/métodos , Neoplasias Pancreáticas/diagnóstico por imagem , Fluorescência , Humanos , Japão , Laparotomia/métodos , Imagem Óptica/métodos , Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Estudos Prospectivos
3.
J Photochem Photobiol B ; 201: 111648, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31710924

RESUMO

Superparamagnetic iron oxide nanoparticles (SPIONs) have been recently recognized as highly efficient photothermal therapy (PTT) agents. Here, we demonstrate, for the first time to our knowledge, dose and laser intensity dependent PTT potential of small, spherical, 3-aminopropyltrimethoxysilane coated cationic superparamagnetic iron oxide nanoparticles (APTMS@SPIONs) in aqueous solutions upon irradiation at 795 nm. Indocyanine green (ICG) which has been recently used for photodynamic therapy (PDT), was loaded to APTMS@SPIONs to improve the stability of ICG and to achieve an effective mild PTT and PDT (dual therapy) combination for synergistic therapeutic effect on cancer cells via a single laser treatment in the near infrared (NIR). Neither APTMS@SPIONs nor ICG-APTMS@SPIONs showed dark toxicity on MCF7 breast and HT29 colon cancer cell lines. A safe laser procedure was determined as 10 min irradiation at 795 nm with 1.8 W/cm2 of laser intensity, at which APTMS@SPION did not cause a significant cell death. However, free ICG reduced cell viability at and above 10 µg/ml under these conditions along with generation of reactive oxygen species (ROS), more effectively in MCF7. ICG-APTMS@SPION treated cells showed 2-fold increase in ROS generation and near complete cell death at and below 5 µg/ml ICG dose, even in less sensitive HT29 cells after a single laser treatment at NIR, which would be safe for the healthy tissue and provide a longer penetration depth. Besides, both components can be utilized for diagnosis and the overall composition may be used for optical-image guided phototherapy in the NIR region.


Assuntos
Verde de Indocianina/química , Nanopartículas de Magnetita/toxicidade , Propilaminas/química , Silanos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Verde de Indocianina/farmacologia , Raios Infravermelhos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/terapia , Fotoquimioterapia , Fototerapia , Espécies Reativas de Oxigênio/metabolismo , Temperatura Ambiente
4.
Chem Commun (Camb) ; 55(84): 12631-12634, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31580341

RESUMO

Mitochondria targeting sensitizers are continuing to gain importance in photodynamic therapy (PDT). Members of the 90 kDa heat shock protein (Hsp90) family, including TRAP1 (Hsp75), are overexpressed in cancer cells and help to control the antiapoptotic protein activity. The present work introduces an Hsp90 inhibitor-mitochondria targeting indocyanine dye conjugate (IR-PU) for high PDT efficacy.


Assuntos
Antineoplásicos/química , Inibidores Enzimáticos/química , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Verde de Indocianina/química , Mitocôndrias/metabolismo , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Corantes Fluorescentes/química , Humanos , Verde de Indocianina/farmacologia , Camundongos , Camundongos Nus , Transplante de Neoplasias , Imagem Óptica/métodos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Oxigênio Singlete/metabolismo
5.
Int J Nanomedicine ; 14: 7823-7838, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576126

RESUMO

Surgery is the frontline treatment for a large number of cancers. The objective of these excisional surgeries is the complete removal of the primary tumor with sufficient safety margins. Removal of the entire tumor is essential to improve the chances of a full recovery. To help surgeons achieve this objective, near-infrared fluorescence-guided surgical techniques are of great interest. The concomitant use of fluorescence and indocyanine green (ICG) has proved effective in the identification and characterization of tumors. Moreover, ICG is authorized by the Food and Drug Administration and the European Medicines Agency and is therefore the subject of a large number of studies. ICG is one of the most commonly used fluorophores in near-infrared fluorescence-guided techniques. However, it also has some disadvantages, such as limited photostability, a moderate fluorescence quantum yield, a high plasma protein binding rate, and undesired aggregation in aqueous solution. In addition, ICG does not specifically target tumor cells. One way to exploit the capabilities of ICG while offsetting these drawbacks is to develop high-performance near-infrared nanocomplexes formulated with ICG (with high selectivity for tumors, high tumor-to-background ratios, and minimal toxicity). In this review article, we focus on recent developments in ICG complexation strategies to improve near-infrared fluorescence-guided tumor surgery. We describe targeted and nontargeted ICG nanoparticle models and ICG complexation with targeting agents.


Assuntos
Verde de Indocianina/química , Neoplasias/cirurgia , Espectroscopia de Luz Próxima ao Infravermelho , Animais , Fluorescência , Humanos , Nanopartículas/química , Distribuição Tecidual
6.
Biomater Sci ; 7(8): 3425-3437, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31268061

RESUMO

Since conventional chemotherapy has a variety of deficiencies and severe side effects, phototherapy has recently aroused great interest worldwide owing to its great potential towards theranostic applications. However, the physiological barrier of tumors hindered the penetration of therapeutic and imaging agents into the center of tumors. In this study, a novel biomimetic nanoplatform inspired by high-density lipoproteins (HDLs) was designed with deep tumor penetrating ability and integrated the clinical imaging agent indocyanine green (ICG) for synergistic phototherapy. Specifically, the HDL-protein was conjugated with the tumor-homing iRGD peptide via an applicable cross-linker to obtain a similar α helix structure, which served as an organizing scaffold for maintaining lipid nanoparticle structure. Our study illustrated that the mimicking nanoparticles shared nanosized diameters and superior biostability compared with free ICG. Once irradiated by NIR light, the encapsulated ICG could produce heat in localized ranges for photothermal therapy (PTT) and sufficient reactive oxygen species (ROS) for photodynamic therapy (PDT). Moreover, the fluorescence of ICG excited by NIR light effectively assisted in diagnosis. After intravenous injection, HDL mimicking nanoparticles could penetrate into deep tumors to realize enhanced phototherapy (PTT and PDT) under NIR laser irradiation. This biomimetic drug delivery system could open an avenue for the production of tailored theranostic nanoplatforms for personalized medicine in the near future.


Assuntos
Materiais Biomiméticos/química , Verde de Indocianina/química , Lipoproteínas HDL/metabolismo , Imagem Molecular/métodos , Nanopartículas/química , Fototerapia/métodos , Nanomedicina Teranóstica/métodos , Animais , Transporte Biológico , Materiais Biomiméticos/metabolismo , Linhagem Celular Tumoral , Verde de Indocianina/metabolismo , Espaço Intracelular/metabolismo , Camundongos , Oligopeptídeos/química , Espécies Reativas de Oxigênio/metabolismo
7.
Artif Cells Nanomed Biotechnol ; 47(1): 2298-2305, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31174440

RESUMO

Photothermal therapy (PTT) is a rapidly developing approach for cancer therapy, which has been widely recognized to exert high efficacy as compared to chemotherapy. However, the limited tumour homing property of currently available drug delivery systems (DDSs) is the bottleneck for the efficient delivery of photothermal agents. Here in this study, we surface modified silica nanoparticles (SLN) with the cell membrane (CM) derived from 143B cells to construct a platform (CM/SLN) capable of targeting the homogenous 143B cells. In addition, indocyanine green (ICG) as a photothermal agent was encapsulated into CM/SLN to finally construct a DDS suitable for tumour-targeted PTT of osteosarcoma. Our results revealed that CM/SLN/ICG was mono-dispersed core-shell nanoparticles with advanced stability in a physiological environment. Moreover, due to the modification of CM, CM/SLN/ICG could specifically target the homogenous 143B cells both in vitro and in vivo, which demonstrated superior anticancer efficacy when compared with either SLN/ICG or free ICG. Hence, CM/SLN/ICG could be a promising DDS for tumour targeted PTT of osteosarcoma.


Assuntos
Membrana Celular/metabolismo , Portadores de Fármacos/química , Verde de Indocianina/química , Nanopartículas/química , Osteossarcoma/tratamento farmacológico , Fotoquimioterapia , Dióxido de Silício/química , Animais , Transporte Biológico , Linhagem Celular Tumoral , Portadores de Fármacos/metabolismo , Feminino , Humanos , Verde de Indocianina/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Osteossarcoma/patologia
8.
Molecules ; 24(12)2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31234288

RESUMO

Molecular and cellular imaging in living organisms have ushered in an era of comprehensive understanding of intracellular and intercellular events. Currently, more efforts have been focused on the infrared fluorescent dyes that facilitate deeper tissue visualization. Both sodium taurocholate cotransporting polypeptide (NTCP) and organic-anion-transporting polypeptide 1B3 (OATP1B3) are capable of carrying indocyanine green (ICG) into the cytoplasm. We compared the feasibility of NTCP and OATP1B3 as reporter genes in combination with ICG. NTCP and OATP1B3 were transduced into HT-29 cells. Genetically modified HT-29 cells were inoculated into nude mice. ICG was administered in vitro and in vivo and the signals were observed under confocal microscopy, flow cytometry, multimode microplate reader, and an in vivo imaging system. Both NTCP- and OATP1B3-expressing cells and xenografts had higher ICG intensities. The OATP1B3-expressing xenograft has a higher ICG uptake than the NTCP-expressing xenograft. NTCP or OATP1B3 combined with ICG could serve as a noninvasive imaging modality for molecular and cellular imaging. OATP1B3 outperforms NTCP in terms of in vivo imaging.


Assuntos
Verde de Indocianina/química , Imagem Óptica , Transportadores de Ânions Orgânicos Dependentes de Sódio/isolamento & purificação , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto/isolamento & purificação , Simportadores/isolamento & purificação , Animais , Genes Reporter/genética , Humanos , Camundongos , Transportadores de Ânions Orgânicos Dependentes de Sódio/química , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto/química , Simportadores/química
9.
Biomater Sci ; 7(8): 3158-3164, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31232421

RESUMO

Indocyanine green (ICG) is a clinically-approved near infrared (NIR) dye used for optical imaging. The dye is only slightly soluble in water and is prone to aggregation in saline solutions, so that alternative formulations can improve photophysical performance. Numerous nanoscale formulations of ICG have been described in the literature, but we sought to develop an approach that does not require additional purification steps. Pre-formed liposomes incorporating 45 mol% of the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) rapidly bind ICG, resulting in enhanced NIR optical properties. ICG binding is dependent on the amount of DOTAP incorporated in the liposomes. A dye-to-lipid mass ratio of [0.5 : 25] is sufficient for full complexation, without additional purification steps following mixing. NIR absorption, fluorescence intensity, and photoacoustic signals are increased for the liposome-bound dye. Not only is the optical character enhanced by simple mixing of ICG with liposomes, but retention in 4T1 mammary tumors is observed following intratumor injection, as assessed by fluorescence and photoacoustic imaging. Subsequent photothermal therapy with 808 nm laser irradiation is effective and results in tumor ablation without regrowth for at least 30 days. Thus, ICG optical properties and photothermal ablation outcomes can be improved by mixing the dye with pre-formed DOTAP liposomes in conditions that result in full dye-binding to the liposomes.


Assuntos
Técnicas de Ablação/métodos , Ácidos Graxos Monoinsaturados/química , Verde de Indocianina/química , Lipossomos/química , Neoplasias Mamárias Experimentais/terapia , Fenômenos Ópticos , Compostos de Amônio Quaternário/química , Animais , Feminino , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Camundongos , Imagem Óptica , Fototerapia
10.
Biomater Sci ; 7(6): 2600-2610, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-30984942

RESUMO

Here, we designed a pH-responsive Indocyanine Green (ICG)-loaded zwitterion fluorescent carbon dot (CD)-encapsulating mesoporous silica nanoparticle (MSN) for pH-tunable image-guided photothermal therapy. ICG was loaded into MSN(CD) via hydrophobic and electrostatic interactions between zwitterionic CDs and ICG to achieve a controlled photothermal temperature with a fluorescent "off/on" system. The porosity of the MSNs was altered after ICG loading because of intermolecular interactions between the CDs and ICG inside the MSN shell and core, which blocked the MSN pore. The acidic environment pH affected the fluorescent signals of the ICG-MSN(CD), reflecting the "off-on" characteristics of the synthesized MSN, which then induced the release of ICG from the matrices. Moreover, the photothermal conversion of ICG-MSN(CD) showed sufficient heat generation to kill cancer cells at an acidic pH with low-temperature elevation at physiological pH. ICG-MSN(CD) demonstrated good cell viability of MDA-MB-231 cells without irradiation; however, high necrosis was observed when the environment was adjusted to acidic pH and after near-infrared irradiation. These pH-responsive photothermal mesoporous silica nanoparticles may have applications in biomedicine, particularly for cancer treatment.


Assuntos
Carbono/química , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Raios Infravermelhos , Nanopartículas/química , Fototerapia , Dióxido de Silício/química , Transporte Biológico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Temperatura Alta , Humanos , Concentração de Íons de Hidrogênio , Verde de Indocianina/química , Verde de Indocianina/metabolismo , Verde de Indocianina/farmacologia , Necrose/induzido quimicamente , Porosidade , Espécies Reativas de Oxigênio/metabolismo
11.
ACS Appl Mater Interfaces ; 11(17): 15262-15275, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30964624

RESUMO

Nanoparticles camouflaged by red blood cell (RBC) membranes have attracted considerable attention owing to reservation of structure of membrane and surface proteins, endowing prominent cell-specific function including biocompatibility, prolonged circulation lifetime, and reduced reticular endothelial system (RES) uptake ability. Considering the drawbacks of carrier-free nanomedicine including the serious drug burst release, poor stability, and lack of immune escape function, herein we developed and fabricated a novel RBC membranes biomimetic combinational therapeutic system by enveloping the small molecular drug coassemblies of 10-hydroxycamptothecin (10-HCPT) and indocyanine green (ICG) in the RBC membranes for prolonged circulation, controlled drug release, and synergistic chemo-photothermal therapy (PTT). The self-reorganized RBCs@ICG-HCPT nanoparticles (NPs) exhibited a diameter of ∼150 nm with core-shell structure, high drug payload (∼92 wt %), and reduced RES uptake function. Taking advantage of the stealth functionality of RBC membranes, RBCs@ICG-HCPT NPs remarkably enhanced the accumulation at the tumor sites by passive targeting followed by cellular endocytosis. Upon the stimuli of near-infrared laser followed by acidic stimulation, RBCs@ICG-HCPT NPs showed exceptional instability by heat-mediated membrane disruption and pH change, thereby triggering the rapid disassembly and accelerated drug release. Consequently, compared with individual treatment, RBCs@ICG-HCPT NPs under dual-stimuli accomplished highly efficient apoptosis in cancer cells and remarkable ablation of tumors by chemo-PTT. This biomimetic nanoplatform based on carrier-free, small molecular drug coassemblies integrating imaging capacity as a promising theranostic system provides potential for cancer diagnosis and combinational therapy.


Assuntos
Antineoplásicos Fitogênicos/química , Biomimética , Camptotecina/análogos & derivados , Membrana Celular/química , Raios Infravermelhos , Nanopartículas/química , Neoplasias/terapia , Animais , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Camptotecina/química , Camptotecina/farmacologia , Camptotecina/uso terapêutico , Eritrócitos/citologia , Eritrócitos/metabolismo , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Verde de Indocianina/química , Masculino , Camundongos , Camundongos Nus , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fototerapia , Ratos , Ratos Sprague-Dawley
12.
Biomater Sci ; 7(5): 2123-2133, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-30869663

RESUMO

Particle-based systems provide a capability for the delivery of imaging and/or therapeutic payloads. We have engineered constructs derived from erythrocytes, and doped with the FDA-approved near infrared dye, indocyanine green (ICG). We refer to these optical particles as NIR erythrocyte-mimicking transducers (NETs). A particular feature of NETs is that their diameters can be tuned from micron- to nano-scale. Herein, we investigated the effects of micron- (≈2.6 µm diameter), and nano- (≈145 nm diameter) sized NETs on their biodistribution, and evaluated their acute toxicity in healthy Swiss Webster mice. Following tail vein injection of free ICG and NETs, animals were euthanized at various time points up to 48 hours. Fluorescence analysis of blood showed that nearly 11% of the injected amount of nano-sized NETs (nNETs) remained in blood at 48 hours post-injection as compared to ≈5% for micron-sized NETs (µNETs). Similarly, at this time point, higher levels of nNETs were present in various organs including the lungs, liver, and spleen. Histological analyses of various organs, extracted at 24 hours post-injection of NETs, did not show pathological alterations. Serum biochemistry profiles, in general, did not show elevated levels of the various analyzed biomarkers associated with liver and kidney functions. Values of various hematological profiles remained within the normal ranges following the administration of µNETs and nNETs. Results of this study suggest that erythrocyte-derived particles can potentially provide a non-toxic platform for delivery of ICG.


Assuntos
Portadores de Fármacos/química , Eritrócitos/metabolismo , Microesferas , Nanopartículas/química , Fenômenos Ópticos , Animais , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/toxicidade , Feminino , Verde de Indocianina/química , Camundongos , Imagem Óptica , Distribuição Tecidual
13.
Adv Mater ; 31(23): e1900192, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30916367

RESUMO

Chimeric antigen receptor (CAR)-redirected T lymphocytes (CAR T cells) show modest therapeutic efficacy in solid tumors. The desmoplastic structure of the tumor and the immunosuppressive tumor microenvironment usually account for the reduced efficacy of CAR T cells in solid tumors. Mild hyperthermia of the tumor reduces its compact structure and interstitial fluid pressure, increases blood perfusion, releases antigens, and promotes the recruitment of endogenous immune cells. Therefore, the combination of mild hyperthermia with the adoptive transfer of CAR T cells can potentially increase the therapeutic index of these cells in solid tumors. It is found that the chondroitin sulfate proteoglycan-4 (CSPG4)-specific CAR T cells infused in Nod scid gamma mice engrafted with the human melanoma WM115 cell line have superior antitumor activity after photothermal ablation of the tumor. The findings suggest that photothermal therapy facilitates the accumulation and effector function of CAR T cells within solid tumors.


Assuntos
Antígenos/metabolismo , Hipertermia Induzida , Imunoterapia Adotiva/métodos , Fototerapia/métodos , Proteoglicanas/metabolismo , Linfócitos T/metabolismo , Microambiente Tumoral , Animais , Linhagem Celular Tumoral , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Terapia Combinada , Feminino , Xenoenxertos , Humanos , Verde de Indocianina/química , Melanoma/patologia , Melanoma/terapia , Proteínas de Membrana/metabolismo , Camundongos SCID , Nanopartículas/química , Fármacos Fotossensibilizantes/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Linfócitos T/transplante
14.
Nanotechnology ; 30(32): 325102, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-30913541

RESUMO

The incorporation of chemo/photothermal/photodynamic therapy in subcellular organelles such as mitochondria has attracted extensive attention recently. Here, we designed mitochondria-targeted hollow mesoporous silica nanoparticles (THMSNs) loaded biocompatible phase-change material L-menthol (LM) via a facile method. Meanwhile, antitumor drug doxorubicin (DOX) and near-infrared (NIR) dye indocyanine green (ICG) approved by FDA were simultaneously encapsulated into THMSNs, denoted as THMSNs@LMDI, which showed NIR radiation triggered capacity for cancer treatment. With the mitochondria-targeted ability of triphenylphosphine, the resulting THMSNs@LMDI showed evidently improved cellular internalization and specific accumulation in mitochondria. Under NIR irradiation, the versatile ICG would be bound to simultaneously produce photodynamic and photothermal therapy. Meanwhile, in view of the solid-liquid phase transition feature of gatekeeper LM, THMSNs@LMDI provided a platform for NIR-mediated temperature-responsive DOX release. As a matter of course, these smart subcellular organelle-THMSNs could serve as an effective drug delivery platform for site-specific on-demand chemo/photothermal/photodynamic therapy of cancer.


Assuntos
Raios Infravermelhos , Mitocôndrias/metabolismo , Nanopartículas/química , Dióxido de Silício/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Materiais Biocompatíveis/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/metabolismo , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Humanos , Verde de Indocianina/química , Verde de Indocianina/metabolismo , Verde de Indocianina/farmacologia , Mentol/química , Mentol/metabolismo , Mentol/farmacologia , Mitocôndrias/efeitos dos fármacos , Nanopartículas/toxicidade , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fotoquimioterapia , Fototerapia , Porosidade , Oxigênio Singlete/metabolismo
15.
Nanoscale ; 11(13): 6217-6227, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30874705

RESUMO

Tumor penetration is the bottleneck for current cancer nanomedicine, limiting the ultimate antitumor efficacy in the clinic. Herein, by exploiting the well-known instability of indocyanine green (ICG), we report the preparation of near infrared (NIR) light responsive nanoparticles (NP) for enhanced tumor penetration. ICG crosslinks hydroxyethyl starch (HES) and doxorubicin (DOX) conjugates (HES-SS-DOX) via noncovalent interactions, facilitating the formation of ICG@HES-SS-DOX NP. The light triggered degradation of ICG leads to the dissociation of such NP, and the resulting HES-SS-DOX has been shown to penetrate deeper in both H22 tumor spheroids and tumor bearing mice, due to the photothermal effect of ICG. Therefore, the disintegrable ICG@HES-SS-DOX NP have better tumor penetration capacity than their counterparts, which originally cannot dissociate under NIR light stimulation. The reported ICG@HES-SS-DOX NP might be potent in treating malignant tumors with dense extracellular matrices, such as liver and pancreatic cancers. This study opens up a novel functionality of FDA-approved ICG for cancer nanotherapeutics.


Assuntos
Verde de Indocianina/química , Raios Infravermelhos , Nanopartículas/química , Animais , Linhagem Celular Tumoral , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Humanos , Derivados de Hidroxietil Amido/química , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Confocal , Nanomedicina , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Transplante Heterólogo
16.
Nanoscale ; 11(13): 6384-6393, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30888375

RESUMO

Photodynamic therapy (PDT) is a clinically approved cancer treatment which utilizes reactive oxygen species (ROS) to eradicate cancer cells. But the high concentration of GSH inside tumor cells can neutralize the generated ROS during PDT, resulting in an insufficient therapeutic effect. To address this issue, we combined ICG-loaded nanoparticles with PEITC for potent PDT. ICG encapsulated in novel hydroxyethyl starch-oleic acid conjugate (HES-OA) nanoparticles (∼50 nm) exhibited excellent stability and efficient singlet oxygen generation under laser irradiation, promoted cellular uptake, and enhanced tumor accumulation, whilst PEITC depleted intracellular GSH significantly. As a result, PDT based on ICG-loaded NPs combined with PEITC synergistically suppressed cancer cells both in vitro and in vivo. Potentiating ICG-loaded NPs with PEITC represents a novel and efficient strategy to enhance PDT efficacy.


Assuntos
Glutationa/metabolismo , Verde de Indocianina/química , Isotiocianatos/química , Nanopartículas/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Células Hep G2 , Humanos , Derivados de Hidroxietil Amido/química , Hipertermia Induzida , Isotiocianatos/farmacocinética , Isotiocianatos/uso terapêutico , Lasers , Camundongos , Microscopia Confocal , Nanopartículas/toxicidade , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Ácido Oleico/química , Fotoquimioterapia , Espécies Reativas de Oxigênio/metabolismo , Oxigênio Singlete/metabolismo , Distribuição Tecidual
17.
Adv Mater ; 31(17): e1808294, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30848011

RESUMO

The ability to selectively kill cancerous cell populations while leaving healthy cells unaffected is a key goal in oncology. The use of nanovesicles (NVs) as chemotherapeutic delivery vehicles has been recently proven successful, yet monotherapy with monomodalities remains a significant limitation for solid tumor treatment. Here, as a proof of principle, a novel cell-membrane-derived NVs that can display full-length monoclonal antibodies (mAbs) is engineered. The high affinity and specificity of mAb for tumor-specific antigens allow these vesicular antibodies (VAs) to selectively deliver a cytotoxic agent to tumor cells and exert potent inhibition effects. These VAs can also regulate the tumor immune microenvironment. They can mediate antibody-dependent cellular cytotoxicity to eradicate tumor cells via recruitment and activation of natural killer cells in the tumor. Upon further encapsulation with chemotherapeutic agents, the VAs show unequaled cooperative effects in chemotherapy and immunotherapy in tumor-bearing mice. As far as it is known, this is the first report of a VA-based multifunctional combination therapy platform. This might lead to additional applications of vesicular antibodies in cancer theranostics.


Assuntos
Anticorpos Monoclonais/imunologia , Portadores de Fármacos/química , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Animais , Anticorpos Monoclonais/genética , Antígenos de Neoplasias/imunologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Transporte Biológico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Terapia Combinada/métodos , Doxorrubicina/química , Doxorrubicina/uso terapêutico , Liberação Controlada de Fármacos , Tratamento Farmacológico/métodos , Humanos , Imunoterapia/métodos , Verde de Indocianina/química , Verde de Indocianina/uso terapêutico , Células Matadoras Naturais/efeitos dos fármacos , Camundongos , Camundongos Nus , Terapia de Alvo Molecular/métodos , Tamanho da Partícula , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Propriedades de Superfície , Microambiente Tumoral/efeitos dos fármacos
18.
Nanoscale ; 11(12): 5717-5731, 2019 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-30865744

RESUMO

Hollow mesoporous structures with interior cavities and expanded surface area have attracted considerable interest as drug delivery systems. In this study, a multifunctional nanotheranostic agent was developed by conjugating indocyanine green (ICG) and loading doxorubicin (DOX) onto the surfaces or within the cavities of hollow mesoporous Prussian blue (HMPB) nanoparticles, known as HMPB@PEI/ICG/DOX or simply HPID NPs, which were investigated as phototheranostic agents for in vivo fluorescence imaging and light-induced chemotherapy, photothermal therapy (PTT) and photodynamic therapy (PDT). These original HPID NPs exhibited strong near infrared (NIR) absorbance, reactive oxygen species (ROS) yield, and controlled chemotherapeutic drug release behavior. After intravenous injection of HPID NPs, highly efficient solid tumor ablation effects were observed in 4T1 tumor-bearing mouse models under NIR laser irradiation. Additionally, there was insignificant low-term toxicity or damage to normal tissues, as evidenced by histopathological and hemocompatibility analyses, suggesting that this agent has reliable biosafety for systemic applications. Taken together, the results of this study suggest that HPID NPs can produce tumor-specific and stimuli-triggered theranostic effects under tri-modal combination therapy. These HPID NPs advantageously provide traceable accumulation and activation and therefore could be a capable mediator in nanomedicines for eliminating solid tumors.


Assuntos
Antibióticos Antineoplásicos/química , Doxorrubicina/química , Ferrocianetos/química , Verde de Indocianina/química , Nanopartículas/química , Animais , Antibióticos Antineoplásicos/metabolismo , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/metabolismo , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Feminino , Humanos , Raios Infravermelhos , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Confocal , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fotoquimioterapia , Porosidade , Distribuição Tecidual
19.
Contrast Media Mol Imaging ; 2019: 7561862, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30718985

RESUMO

Purpose: Paired-agent molecular imaging methods, which employ coadministration of an untargeted, "control" imaging agent with a targeted agent to correct for nonspecific uptake, have been demonstrated to detect 200 cancer cells in a mouse model of metastatic breast cancer. This study demonstrates that indocyanine green (ICG), which is approved for human use, is an ideal control agent for future paired-agent studies to facilitate eventual clinical translation. Methods: The kinetics of ICG were compared with a known ideal control imaging agent, IRDye-700DX-labeled antibody in both healthy and metastatic rat popliteal lymph nodes after coadministration, intradermally in the footpad. Results: The kinetics of ICG and antibody-based imaging agent in tumor-free rat lymph nodes demonstrated a strong correlation with each other (r = 0.98, p < 0.001) with a measured binding potential of -0.102 ± 0.03 at 20 min postagent injection, while the kinetics of ICG and targeted imaging agent shows significant separation in the metastatic lymph nodes. Conclusion: This study indicated a potential for microscopic sensitivity to cancer spread in sentinel lymph nodes using ICG as a control agent for antibody-based molecular imaging assays.


Assuntos
Verde de Indocianina/química , Linfonodos/diagnóstico por imagem , Imagem Óptica/métodos , Linfonodo Sentinela/diagnóstico por imagem , Animais , Feminino , Cinética , Camundongos , Ratos
20.
Biomater Sci ; 7(4): 1705-1715, 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30758351

RESUMO

Indocyanine green (ICG), a multifunctional near-infrared (NIR) imaging agent approved by the FDA, has been extensively used in clinical cancer theranosis, but limited by its inherent instability, short plasma half-life and lack of targeting ability. Herein, an in situ formed photothermal network based thermosensitive hydrogel (PNT-gel) constructed by using supramolecular cross-linking conjugated polymers was developed for the stabilization of ICG and efficient combinatorial photothermal/photodynamic antitumor therapy. While the conjugated polymeric backbone in PNT-gel anchored the aromatic phototherapeutic agent ICG via π-π stacking interactions to avoid premature leakage, it also directly converted low-dose NIR light to induce localized hyperthermia to enhance the photothermal effect. The PNT-gel shows a reversible gel-to-sol upper critical solution temperature (UCST) that is slightly above body temperature. Therefore, the controlled release of ICG was switched on or off by NIR via photothermal-induced gel-sol transition. In vitro and in vivo antitumor experiments demonstrated that ICG loaded PNT-gel not only efficiently induced the killing of 4T1 cancer cells, but also achieved almost complete eradication of 4T1 cells by one-dose intratumoral injection in combinatorial photothermal/photodynamic therapy under irradiation of a low-dose 808 nm laser (0.14 W cm-2). Additionally, the combinational therapy proved to enhance the effectiveness of photodestruction without tumor recurrence compared with photothermal therapy (PTT) or photodynamic therapy (PDT) treatment alone.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Corantes/química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Verde de Indocianina/química , Fármacos Fotossensibilizantes/farmacologia , Fototerapia , Animais , Antineoplásicos/química , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Terapia Combinada , Modelos Animais de Doenças , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Raios Infravermelhos , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos , Camundongos Nus , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo , Temperatura Ambiente
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