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1.
Chem Commun (Camb) ; 56(7): 1093-1096, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31894764

RESUMO

We prepared novel conjugated polymer based NIR-II nanoparticles, which display extremely high photothermal conversion efficiency (65%). Both in vitro and in vivo investigations revealed that the as-prepared nanoparticles exhibit excellent theranostic properties including an extremely high cancer cell killing ability, admirable tumor elimination efficiency (100%) and a remarkable photoacoustic imaging contrast enhancing ability.


Assuntos
Antineoplásicos/uso terapêutico , Nanopartículas/uso terapêutico , Compostos de Organossilício/uso terapêutico , Polímeros/uso terapêutico , Tiadiazóis/uso terapêutico , Animais , Antineoplásicos/química , Antineoplásicos/efeitos da radiação , Células Hep G2 , Humanos , Hipertermia Induzida/métodos , Raios Infravermelhos , Camundongos , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Nanopartículas/química , Nanopartículas/efeitos da radiação , Compostos de Organossilício/química , Compostos de Organossilício/efeitos da radiação , Técnicas Fotoacústicas/métodos , Polímeros/química , Polímeros/efeitos da radiação , Nanomedicina Teranóstica/métodos , Tiadiazóis/química , Tiadiazóis/efeitos da radiação
2.
Yakugaku Zasshi ; 140(1): 7-13, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-31902888

RESUMO

Matrix metalloproteinases (MMPs) regulate various cellular functions, such as motility, invasion, differentiation, and apoptosis. Precise in vivo quantification of MMPs in disease can provide beneficial information for both basic and clinical research studies. To this end, various types of probes have been developed for imaging MMPs in vivo. In this review, representative MMP-targeted probes, such as binding probes and activatable probes, are outlined, including highlights of our own research. In addition, strategies for the development of probes that apply "theranostics," a concept that integrates therapy and diagnostics, are elucidated with reference to [18F]IPFP, a new probe developed in our laboratory. [18F]IPFP was prepared by iodination of a known MMP inhibitor to enhance its affinity and labeled with the compact prosthetic agent 4-nitrophenyl 2-[18F]fluoropropionate ([18F]NFP) for MMP-targeted positron-emission tomography (PET) and other therapeutic properties. IPFP demonstrated high inhibitory activity toward MMP-12 (IC50 value=1.5 nM). Radioactivity accumulation in the lungs 90 min after administration of [18F]IPFP was 4-fold higher in chronic obstructive pulmonary disease (COPD) mice overexpressing MMPs compared with normal mice. Ex vivo PET confirmed the radioactivity distribution in tissues, and autoradiography analysis demonstrated accumulation differences between COPD and normal mice. Consequently, [18F]IPFP showed potent inhibitory activities against MMPs and suitable pharmacokinetics for imaging pulmonary disease. Thus, [18F]IPFP is a promising theranostic probe for pulmonary disease and is expected to be applied to various other MMP-related diseases. Strategies for MMP probe development introduced in this review are anticipated to lead to the development of superior imaging probes in the future.


Assuntos
Corantes Fluorescentes , Metaloproteinases da Matriz/análise , Imagem Molecular/métodos , Animais , Biomarcadores/análise , Radioisótopos de Flúor , Humanos , Metaloproteinases da Matriz/fisiologia , Camundongos , Tomografia por Emissão de Pósitrons , Doença Pulmonar Obstrutiva Crônica , Compostos Radiofarmacêuticos , Nanomedicina Teranóstica , Tomografia Computadorizada de Emissão de Fóton Único
3.
Chem Commun (Camb) ; 56(10): 1464-1480, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-31967621

RESUMO

This review discusses the advantages of using luminescent d6-transition-metal complexes as cell probes for optical microscopy. In particular it focusses on the Thomas group's use of specific complexes as "building blocks" toward the construction of biomolecular binding substrates, with DNA being a particular target. Using this approach, a range of new imaging probes for conventional optical microscopy, nanoscopy and transmission electron microscopy have been identified. Through selection of specific metal centres and by substitution of coordinated ligands we illustrate how new chemotherapeutics, photo-therapeutics, and theranostics have been identified and developed from the original architectures.


Assuntos
Complexos de Coordenação/química , DNA/química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Apoptose/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Meios de Contraste/química , Meios de Contraste/metabolismo , Complexos de Coordenação/metabolismo , Complexos de Coordenação/toxicidade , DNA/metabolismo , Humanos , Sondas Moleculares/química , Sondas Moleculares/metabolismo , Nanomedicina Teranóstica
4.
Chem Soc Rev ; 49(4): 1144-1172, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-31971181

RESUMO

The emergence of aggregation-induced emission luminogens (AIEgens) has significantly stimulated the development of luminescent supramolecular materials because their strong emissions in the aggregated state have resolved the notorious obstacle of the aggregation-caused quenching (ACQ) effect, thereby enabling AIEgen-based supramolecular materials to have a promising prospect in the fields of luminescent materials, sensors, bioimaging, drug delivery, and theranostics. Moreover, in contrast to conventional fluorescent molecules, the configuration of AIEgens is highly twisted in space. Investigating AIEgens and the corresponding supramolecular materials provides fundamental insights into the self-assembly of nonplanar molecules, drastically expands the building blocks of supramolecular materials, and pushes forward the frontiers of supramolecular chemistry. In this review, we will summarize the basic concepts, seminal studies, recent trends, and perspectives in the construction and applications of AIEgen-based supramolecular materials with the hope to inspire more interest and additional ideas from researchers and further advance the development of supramolecular chemistry.


Assuntos
Substâncias Luminescentes/química , Imagem Óptica , Nanomedicina Teranóstica , DNA/química , Portadores de Fármacos/química , Humanos , Compostos Macrocíclicos/química , Microscopia Confocal , Neoplasias/diagnóstico por imagem , Peptídeos/química
5.
Chem Soc Rev ; 49(4): 1253-1321, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-31998912

RESUMO

Studies of nanosized forms of bismuth (Bi)-containing materials have recently expanded from optical, chemical, electronic, and engineering fields towards biomedicine, as a result of their safety, cost-effective fabrication processes, large surface area, high stability, and high versatility in terms of shape, size, and porosity. Bi, as a nontoxic and inexpensive diamagnetic heavy metal, has been used for the fabrication of various nanoparticles (NPs) with unique structural, physicochemical, and compositional features to combine various properties, such as a favourably high X-ray attenuation coefficient and near-infrared (NIR) absorbance, excellent light-to-heat conversion efficiency, and a long circulation half-life. These features have rendered bismuth-containing nanoparticles (BiNPs) with desirable performance for combined cancer therapy, photothermal and radiation therapy (RT), multimodal imaging, theranostics, drug delivery, biosensing, and tissue engineering. Bismuth oxyhalides (BiOx, where X is Cl, Br or I) and bismuth chalcogenides, including bismuth oxide, bismuth sulfide, bismuth selenide, and bismuth telluride, have been heavily investigated for therapeutic purposes. The pharmacokinetics of these BiNPs can be easily improved via the facile modification of their surfaces with biocompatible polymers and proteins, resulting in enhanced colloidal stability, extended blood circulation, and reduced toxicity. Desirable antibacterial effects, bone regeneration potential, and tumor growth suppression under NIR laser radiation are the main biomedical research areas involving BiNPs that have opened up a new paradigm for their future clinical translation. This review emphasizes the synthesis and state-of-the-art progress related to the biomedical applications of BiNPs with different structures, sizes, and compositions. Furthermore, a comprehensive discussion focusing on challenges and future opportunities is presented.


Assuntos
Bismuto/química , Nanopartículas Metálicas/química , Nanomedicina Teranóstica , Técnicas Biossensoriais , Regeneração Óssea , Meios de Contraste/síntese química , Meios de Contraste/química , Humanos , Nanopartículas Metálicas/uso terapêutico , Imagem Multimodal , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Fototerapia
6.
J Biomed Nanotechnol ; 16(1): 125-135, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31996291

RESUMO

Theranostic nanosystems encompassing imaging reagents and therapeutic genes are promising for concurrent tumor diagnosis and gene therapy. In this work, we developed bioresponsive gadolinium (Gd)-based nanopolyplexes (denoted as Gdplexes) for in vivo tumor theranostic applications. Gdplexes were generated by a hierarchical assembly method involving the neutralization of DNA with a Gd-chelated bioreducible cationic polyurethane (termed as GdCPUA), which was followed by condensation of DNA with a cationic dextran conjugate (DP800). By adjusting GdCPUA/DP800 ratios, the resultant Gdplexes had GdCPUA/DNA complex as an inner core and a dextran outer shell; thus, Gdplexes exhibit an improved colloidal stability under physiological conditions and perform active gene release in an intracellular reductive environment. In vitro tests against cancer cells revealed that optimized Gdplexes afforded comparable transfection efficiency to that of the 25 kDa branched polyethylenimine used as a positive control. Additionally, the Gdplexes could robustly transfer small hairpin RNA plasmids to silence vascular endothelial growth factor expression in SKOV-3 cells. In vivo, the Gdplexes loaded with plasmid were practical for systemic gene delivery via intravenous administration, yielding marked growth repression of an SKOV-3 tumor xenograft in a BALB/c nude mouse model. The tumor could be visualized by T1-weighted magnetic resonance (MR) imaging. Such efficient gene therapy had no adverse effects on hepatorenal functions and weight gain in the mouse. This work highlights Gdplexes as biosafe and robust nanocarriers for tumor theranostic applications in vivo.


Assuntos
Nanomedicina Teranóstica , Animais , Linhagem Celular Tumoral , Terapia Genética , Imagem por Ressonância Magnética , Camundongos , Camundongos Endogâmicos BALB C , Fator A de Crescimento do Endotélio Vascular
7.
Chemistry ; 26(7): 1668-1675, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31814171

RESUMO

Despite drug delivery nanoplatforms receiving extensive attention, development of a simple, effective, and multifunctional theranostics nanoplatform still remains a challenge. Herein, a versatile nanoplatform based on a zirconium framework (UiO-66-N3 ) was synthesized, which demonstrated a combined photodynamic therapy (PDT), photothermal therapy (PTT), and chemotherapy (CT) for cancer treatment. A RuII polypyridyl alkyne complex (Ra) as a photosensitizer was modified into a nanoplatform by click reactions for the first time. When exposed to suitable light irradiation, the as-prepared multifunctional nanoplatform (UiO-Ra-DOX-CuS) not only demonstrated efficient 1 O2 generation, but also exhibited excellent photothermal conversion ability. In particular, the nanotherapeutic agent presented a dual-stimuli response; either acidic environment or NIR laser irradiation would trigger the drug release. The synergetic efficacy of UiO-Ra-DOX-CuS combined PDT, PTT, and CT, which was evaluated by cell experiments. Moreover, the design could promote the development of RuII polypyridyl alkyne complexes based multifunctional nanoparticles and multimodal cancer treatment.


Assuntos
Alquinos/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Compostos de Rutênio/química , Terapia Combinada , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Quimioterapia Combinada , Humanos , Estruturas Metalorgânicas , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Nanomedicina Teranóstica
8.
Anal Bioanal Chem ; 412(1): 37-54, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31734711

RESUMO

Metal-organic frameworks (MOFs) have emerged as one of the most fascinating libraries of porous materials with a huge potential in very diverse application areas. In particular, the bioanalytical and biomedical fields have evolved tremendously due to the emergence of these hybrid inorganic-organic MOF-based materials. This is because these materials possess a series of key properties essential for bioapplications, such as minimal toxicity to living cells, intrinsic biodegradability, and possibility of synthesizing with nanoscale sizes. Additional properties of MOFs such as ultra-large surface-to-volume ratios, tunable pore size, high drug loading capacity, tunable structure and chemical composition, and potential for multiple postsynthetic modification make them ideal candidates for drug delivery. This review highlights recent research progress on MOF-based drug delivery systems (DDS), pointing out the evolution of these systems toward the development of theranostic nanoplatforms. Rather than a comprehensive review, representative recent examples are selected to illustrate such an evolution, and a critical discussion of the advantages and limitations of the different DDS types is given. Finally, the remaining challenges and future opportunities in this field are presented, highlighting that overcoming the current issues will pave the way toward the elusive dream of "personalized medicine." Graphical Abstract.


Assuntos
Sistemas de Liberação de Medicamentos , Estruturas Metalorgânicas/química , Nanoestruturas , Nanomedicina Teranóstica
10.
J Nanobiotechnology ; 17(1): 126, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31870376

RESUMO

BACKGROUND: An important but rarely addressed question in nano-therapy is to know whether bio-degraded nanoparticles with reduced sizes and weakened heating power are able to maintain sufficient anti-tumor activity to fully eradicate a tumor, hence preventing tumor re-growth. To answer it, we studied magnetosomes, which are nanoparticles synthesized by magnetotactic bacteria with sufficiently large sizes (~ 30 nm on average) to enable a follow-up of nanoparticle sizes/heating power variations under two different altering conditions that do not prevent anti-tumor activity, i.e. in vitro cellular internalization and in vivo intra-tumor stay for more than 30 days. RESULTS: When magnetosomes are internalized in U87-Luc cells by being incubated with these cells during 24 h in vitro, the dominant magnetosome sizes within the magnetosome size distribution (DMS) and specific absorption rate (SAR) strongly decrease from DMS ~ 40 nm and SAR ~ 1234 W/gFe before internalization to DMS ~ 11 nm and SAR ~ 57 W/gFe after internalization, a behavior that does not prevent internalized magnetosomes to efficiently destroy U87-Luc cell, i.e. the percentage of U87-Luc living cells incubated with magnetosomes decreases by 25% between before and after alternating magnetic field (AMF) application. When 2 µl of a suspension containing 40 µg of magnetosomes are administered to intracranial U87-Luc tumors of 2 mm3 and exposed (or not) to 15 magnetic sessions (MS), each one consisting in 30 min application of an AMF of 27 mT and 198 kHz, DMS and SAR decrease between before and after the 15 MS from ~ 40 nm and ~ 4 W/gFe down to ~ 29 nm and ~ 0 W/gFe. Although the magnetosome heating power is weakened in vivo, i.e. no measurable tumor temperature increase is observed after the sixth MS, anti-tumor activity remains persistent up to the 15th MS, resulting in full tumor disappearance among 50% of treated mice. CONCLUSION: Here, we report sustained magnetosome anti-tumor activity under conditions of significant magnetosome size reduction and complete loss of magnetosome heating power.


Assuntos
Antineoplásicos/química , Neoplasias Encefálicas/tratamento farmacológico , Nanopartículas de Magnetita/química , Magnetossomos/química , Magnetospirillum/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular , Feminino , Calefação , Humanos , Hipertermia Induzida , Campos Magnéticos , Camundongos , Camundongos Nus , Tamanho da Partícula , Nanomedicina Teranóstica/métodos , Distribuição Tecidual
11.
J Nanobiotechnology ; 17(1): 122, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842876

RESUMO

Obesity through its association with type 2 diabetes (T2D), cancer and cardiovascular diseases (CVDs), poses a serious health threat, as these diseases contribute to high mortality rates. Pharmacotherapy alone or in combination with either lifestyle modification or surgery, is reliable in maintaining a healthy body weight, and preventing progression to obesity-induced diseases. However, the anti-obesity drugs are limited by non-specificity and unsustainable weight loss effects. As such, novel and improved approaches for treatment of obesity are urgently needed. Nanotechnology-based therapies are investigated as an alternative strategy that can treat obesity and be able to overcome the drawbacks associated with conventional therapies. The review presents three nanotechnology-based anti-obesity strategies that target the white adipose tissues (WATs) and its vasculature for the reversal of obesity. These include inhibition of angiogenesis in the WATs, transformation of WATs to brown adipose tissues (BATs), and photothermal lipolysis of WATs. Compared to conventional therapy, the targeted-nanosystems have high tolerability, reduced side effects, and enhanced efficacy. These effects are reproducible using various nanocarriers (liposomes, polymeric and gold nanoparticles), thus providing a proof of concept that targeted nanotherapy can be a feasible strategy that can combat obesity and prevent its comorbidities.


Assuntos
Fármacos Antiobesidade/química , Portadores de Fármacos/química , Nanopartículas/química , Obesidade/tratamento farmacológico , Indutores da Angiogênese/metabolismo , Inibidores da Angiogênese/química , Inibidores da Angiogênese/farmacologia , Animais , Fármacos Antiobesidade/farmacologia , Liberação Controlada de Fármacos , Ouro/química , Humanos , Lipídeos/química , Polímeros/química , Nanomedicina Teranóstica , Resultado do Tratamento
12.
Presse Med ; 48(10): 1092-1100, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31706893

RESUMO

In France, breast cancer is the most common cancer among women and the leading cause of cancer deaths. Identifying women with a "high" or "very high" breast cancer risk, according the terminology of the Haute Autorité de Santé 2014 guidelines, is essential to offer them special cares in term of screening and prevention. Women genetically predisposed have a very high risk of breast cancer. During the oncogenetic specialist consultation, familial and personal history of cancer is taken into account to evaluate the risk of hereditary Breast/Ovarian syndrome and thus the need of a genetic screening. In 2017, a list of 13 genes involved in hereditary ovarian or breast cancer has been established in France (Genetic and Cancer Group - Unicancer). Women carrying a BRCA1, BRCA2, PALB2, TP53, CDH1, PTEN mutation have a higher risk of breast cancer and are considered as "high risk". Therefore, medical breast surveillance similar to carriers of BRCA1/BRCA2 mutation is recommended for these patients (INCa guidelines 2017). However a mutation in one of those genes is only identified in approximatively 10 % of the screened families. The oncogenetic specialist's assessment distinguishes families in which women remain at a "high" risk of breast cancer (HAS 2014 for screening) from those where women have a "very high" risk (INCa guidelines 2017 for screening and prevention).


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Mutação , Fatores Etários , Antígenos CD/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Neoplasias da Mama Masculina/genética , Caderinas/genética , Saúde da Família , Proteína do Grupo de Complementação N da Anemia de Fanconi/genética , Feminino , França , Genes BRCA1 , Genes BRCA2 , Genes p53 , Testes Genéticos , Síndrome do Hamartoma Múltiplo/genética , Humanos , Síndrome de Li-Fraumeni/genética , Masculino , Neoplasias Ovarianas/genética , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Gravidez , Mastectomia Profilática , Fatores de Risco , Nanomedicina Teranóstica , Neoplasias de Mama Triplo Negativas/genética
13.
Int J Nanomedicine ; 14: 6661-6678, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695362

RESUMO

Background: Cancer treatments are being continually developed. Increasingly more effective and better-targeted treatments are available. As treatment has developed, the outcomes have improved. Purpose: In this work, polyethylene glycol (PEG), layered double hydroxide (LDH) and 5-fluorouracil (5-FU) were used as a stabilizing agent, a carrier and an anticancer active agent, respectively. Characterization and methods: Magnetite nanoparticles (Fe3O4) coated with polyethylene glycol (PEG) and co-coated with 5-fluorouracil/Mg/Al- or Zn/Al-layered double hydroxide were synthesized by co-precipitation technique. Structural, magnetic properties, particle shape, particle size and drug loading percentage of the magnetic nanoparticles were investigated by XRD, TGA, FTIR, DLS, FESEM, TEM, VSM, UV-vis spectroscopy and HPLC techniques. Results: XRD, TGA and FTIR studies confirmed the formation of Fe3O4 phase and the presence of iron oxide nanoparticles, polyethylene glycol, LDH and the drug for all the synthesized samples. The size of the nanoparticles co-coated with Mg/Al-LDH is about 27 nm compared to 40 nm when they were co-coated with Zn/Al-LDH, with both showings near uniform spherical shape. The iron oxide nanoparticles retain their superparamagnetic property when they were coated with polyethylene glycol, polyethylene glycol co-coated with Mg/Al-LDH and polyethylene glycol co-coated with Zn/Al-LDH with magnetic saturation value of 56, 40 and 27 emu/g, respectively. The cytotoxicity study reveals that the anticancer nanodelivery system has better anticancer activity than the free drug, 5-FU against liver cancer HepG2 cells and at the same time, it was found to be less toxic to the normal fibroblast 3T3 cells. Conclusion: These are unique core-shell nanoparticles synthesized with the presence of multiple functionalities are hoped can be used as a multifunctional nanocarrier with the capability of targeted delivery using an external magnetic field and can also be exploited as hypothermia for cancer cells in addition to the chemotherapy property.


Assuntos
Fluoruracila/farmacologia , Hidróxidos/química , Fenômenos Magnéticos , Polietilenoglicóis/química , Nanomedicina Teranóstica , Células 3T3 , Animais , Antineoplásicos/farmacologia , Morte Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Difusão Dinâmica da Luz , Células Hep G2 , Humanos , Concentração Inibidora 50 , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/ultraestrutura , Camundongos , Tamanho da Partícula , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura Ambiente , Difração de Raios X
14.
Chem Commun (Camb) ; 55(95): 14387-14390, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31723950

RESUMO

We designed a tandem stimuli-responsive assembly based on a guanidinium-modified calix[5]arene (GC5A-6C) and eosin Y modified hyaluronic acid (EY-HA), which showed hyaluronidase-triggered disassembly and ATP-activated release of EY. Both hyaluronidase and ATP are tumor biomarkers, and therefore, the present system shows potential in precision delivery with respect to tumor phototheranostics.


Assuntos
Trifosfato de Adenosina/metabolismo , Calixarenos/metabolismo , Amarelo de Eosina-(YS)/metabolismo , Guanidina/metabolismo , Ácido Hialurônico/metabolismo , Hialuronoglucosaminidase/metabolismo , Trifosfato de Adenosina/química , Biomarcadores Tumorais/química , Biomarcadores Tumorais/metabolismo , Calixarenos/química , Amarelo de Eosina-(YS)/química , Guanidina/química , Humanos , Ácido Hialurônico/química , Hialuronoglucosaminidase/química , Substâncias Macromoleculares/química , Substâncias Macromoleculares/metabolismo , Polímeros/química , Polímeros/metabolismo , Nanomedicina Teranóstica , Microambiente Tumoral
15.
Chem Commun (Camb) ; 55(98): 14844-14847, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31768507

RESUMO

Ultrasmall sub-10 nm nanoparticles of Prussian blue analogues incorporating GdIII ions at their periphery revealed longitudinal relaxivities above 40 mM-1 s-1 per GdIII regardless of the nature of the core and the polymer coating. Large T1-weighted contrast enhancements were achieved in addition to a highly efficient photothermal effect and in vivo photoacoustic imaging in tumors.


Assuntos
Ferrocianetos/química , Imagem por Ressonância Magnética/métodos , Nanopartículas/química , Nanomedicina Teranóstica , Animais , Linhagem Celular Tumoral , Meios de Contraste/química , Gadolínio/química , Humanos , Camundongos , Neoplasias/diagnóstico por imagem , Transplante Heterólogo
16.
Crit Rev Ther Drug Carrier Syst ; 36(4): 305-371, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679190

RESUMO

Ovarian cancer (OC) has emerged as one of the leading causes of death in women due to the lack of early-stage diagnosis resulting in impairment and delay in treatment of malignancy, which raises the morality rate. Existing diagnostic (pelvic examination, CA125, and enzyme-linked immunosorbent assay) or therapeutic modalities (radiotherapy, abdominal pelvic radiation therapy, and chemotherapy) are insufficient to decrease the 5-year survival rate. Nanoparticles (NPs) have been extensively explored as probes for imaging or therapy of cancer. As an extension of this, probes have been designed to possess both imaging and therapeutic modality in a single molecule and this has emerged as the science of nanotheranostics. This review presents the existing diagnostic and therapeutic strategies in use for OC and discusses their loopholes that limit the prognosis of OC. The review presents a general description of important properties of nanostructures and the type of nanostructures that have been used as imaging/therapeutic probe in cancer. The state-of-the-art nanotheranostics probe for targeting OC is presented. Systematic and complete studies that can correlate the findings of researchers from different global areas are lacking. The current status of nanostructures in various phases of clinical trials and those approved by U.S. Food and Drug Administration (FDA) has been presented. No specific targeted theranostic probe for OC has yet been approved by the FDA. Here, the underlying reasons and the challenges faced for nanotheranostics of OC are discussed, along with its future prospects.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/terapia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/terapia , Nanomedicina Teranóstica/métodos , Animais , Antineoplásicos/química , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/genética , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/química , RNA Interferente Pequeno/genética , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Int J Nanomedicine ; 14: 6749-6777, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31692550

RESUMO

Janus particles, which are named after the two-faced Roman god Janus, have two distinct sides with different surface features, structures, and compositions. This asymmetric structure enables the combination of different or even incompatible physical, chemical, and mechanical properties within a single particle. Much effort has been focused on the preparation of Janus particles with high homogeneity, tunable size and shape, combined functionalities, and scalability. With their unique features, Janus particles have attracted attention in a wide range of applications such as in optics, catalysis, and biomedicine. As a biomedical device, Janus particles offer opportunities to incorporate therapeutics, imaging, or sensing modalities in independent compartments of a single particle in a spatially controlled manner. This may result in synergistic actions of combined therapies and multi-level targeting not possible in isotropic systems. In this review, we summarize the latest advances in employing Janus particles as therapeutic delivery carriers, in vivo imaging probes, and biosensors. Challenges and future opportunities for these particles will also be discussed.


Assuntos
Diagnóstico por Imagem/métodos , Sistemas de Liberação de Medicamentos/métodos , /uso terapêutico , Nanomedicina Teranóstica/métodos , Animais , Técnicas Biossensoriais , Meios de Contraste/química , Humanos , Polímeros/química
18.
Int J Nanomedicine ; 14: 7017-7038, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564863

RESUMO

Background: Fabrication of a smart drug delivery system that could dramatically increase the efficiency of chemotherapeutic drugs and reduce the side effects is still a challenge for pharmaceutical researchers. By the emergence of nanotechnology, a huge window was opened towards this goal, and a wide type of nanocarriers were introduced for delivering the chemotherapeutic to the cancer cells, among them are cyclodextrins with the ability to host different types of hydrophobic bioactive molecules through inclusion complexation process. Aim: The aim of this study is to design and fabricate a pH-responsive theranostic nanocapsule based on cyclodextrin supramolecular nano-structure. Materials and methods: This nanostructure contains iron oxide nanoparticles in the core surrounded with three polymeric layers including polymeric ß-cyclodextrin, polyacrylic acid conjugated to sulfadiazine, and polyethylenimine functionalized with ß-cyclodextrin. Sulfadiazine is a pH-responsive hydrophobic component capable of making inclusion complex with ß-cyclodextrin available in the first and third layers. Doxorubicin, as an anti-cancer drug model, was chosen and the drug loading and release pattern were determined at normal and acidic pH. Moreover, the biocompatibility of the nanocapsule (with/without drug component) was examined using different techniques such as MTT assay, complement activation, coagulation assay, and hemolysis. Results: The results revealed the successful preparation of a spherical nanocapsule with mean size 43±1.5 nm and negatively charge of -43 mV that show 160% loading efficacy. Moreover, the nanocapsule has an on/off switching release pattern in response to pH that leads to drug released in low acidic pH. The results of the biocompatibility tests indicated that this nano drug delivery system had no effect on blood and immune components while it could affect cancer cells even at very low concentrations (0.3 µg mL-1). Conclusion: The obtained results suggest that this is a "switchable" theranostic nanocapsule with potential application as an ideal delivery system for simultaneous cancer diagnosis and therapy.


Assuntos
Nanocápsulas/química , Polietilenoimina/química , Nanomedicina Teranóstica , beta-Ciclodextrinas/química , Animais , Doxorrubicina/química , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Compostos Férricos/química , Hemólise/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Camundongos , Nanocápsulas/ultraestrutura , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Eletricidade Estática , Compostos de Sulfidrila/síntese química , Compostos de Sulfidrila/química , Difração de Raios X , beta-Ciclodextrinas/síntese química
19.
Int J Nanomedicine ; 14: 7079-7093, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564866

RESUMO

Background: Currently, effective detection and treatment of cutaneous malignant melanoma (CMM) still face severe challenges. Ultrasound molecular imaging as a noninvasive and easy-to-operate method is expected to bring improvements for tumor detection. Purpose: The aim of this research is to prepare novel phase-change ultrasound contrast agents, Nds-IR780, which can perform not only dual-mode molecule-targeted imaging but also targeted photothermal therapy for CMM. Methods: A double emulsion process was used to prepare the Nds-IR780. Then, the entrapment rate and drug loading of IR-780 iodide in Nds-IR780 were detected by high-performance liquid chromatography. The biocompatibility of Nds-IR780 was evaluated by a CCK-8 assay and the characteristics and stability of that were verified through the particle size analyzer, laser scanning confocal microscopy (LSCM) and transmission electron microscopy (TEM). The abilities of dual-mode molecule-targeted imaging and targeted photothermal therapy for Nds-IR780 were confirmed via the in vitro and in vivo experiments. Results: Nds-IR780 had good size distribution, polydispersity index, stability and biosafety. The in vitro and in vivo experiments confirmed that Nds-IR780 were capable of targeting CMM cells with high affinity (22.4±3.2%) and facilitating dual-mode imaging to detect the primary lesion and sentinel lymph nodes (SLNs) of CMM. Furthermore, the photothermal ablation of CMM mediated by Nds-IR780 was very effective in vivo. Conclusion: The newly prepared Nds-IR780 were observed to be effective targeted theranostic probe for the precise detection and targeted treatment of CMM.


Assuntos
Meios de Contraste/química , Gotículas Lipídicas/química , Melanoma/diagnóstico , Melanoma/terapia , Nanopartículas/química , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/terapia , Nanomedicina Teranóstica , Animais , Materiais Biocompatíveis/química , Linhagem Celular Tumoral , Humanos , Hipertermia Induzida , Indóis/química , Camundongos Endogâmicos BALB C , Camundongos Nus , Fototerapia , Temperatura Ambiente , Distribuição Tecidual , Carga Tumoral , Ultrassom
20.
Int J Nanomedicine ; 14: 7141-7153, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564870

RESUMO

Background: Theranostics, elaborately integrating both therapeutic and diagnostic functions into a nanoplatform holds great potential for precision cancer medicine. Methods: Herein, a biodegradable theranostic nanoplatform with hyperthermia-induced bubble ability for highly efficient ultrasound (US) imaging-guided chemo-photothermal therapy of breast tumors was developed. The prepared nanoparticles consisted of polydopamine (PDA)-modified hollow mesoporous organosilica nanoparticles (HMONs) with approximately 75 nm in diameter for doxorubicin (DOX) loading and perfluoropentane (PFP) filling. In addition, the pH-sensitive PDA coating served as both gatekeeper controlling DOX release and photothermal agent for inducing hyperthermia. Results: Such nanoplatform (PDA@HMONs-DOX/PFP, PHDP) provides efficient loading (328 mg/g) and controllable stimuli-responsive release of DOX for chemotherapy. The incorporated disulfide bonds in the framework of HMONs endowed nanoparticles with intrinsic glutathione-responsive biodegradability and improved biocompatibility. Benefiting from the hyperthermia upon an 808-nm laser irradiation of PDA, the liquid-gas phase transition of the loaded PFP was induced, resulting in the generation of the nanobubbles, followed by the coalescence into microbubbles. This conversation could enhance the tumor cell uptake of nanoparticles, as well as intensify the US imaging signals. In addition, a synergistic therapeutic effect of our fabricated nanoplatform on cells/tumor growth effect has been systematically evaluated both in vitro and in vivo. Conclusion: Therefore, such "all-in-one" PHDP nanoparticles with satisfactory biocompatibility and biodegradability, hyperthermia-induced bubble ability and simultaneous US imaging performance hold great potential for cancer nanotheranostics.


Assuntos
Hipertermia Induzida , Microbolhas , Nanopartículas/química , Fototerapia , Nanomedicina Teranóstica , Ultrassonografia , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Liberação Controlada de Fármacos , Sinergismo Farmacológico , Endocitose/efeitos dos fármacos , Feminino , Humanos , Indóis/química , Cinética , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/ultraestrutura , Polímeros/química , Distribuição Tecidual/efeitos dos fármacos
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