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1.
J Am Chem Soc ; 133(8): 2583-91, 2011 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-21294543

RESUMO

Efficient drug delivery to tumors is of ever-increasing importance. Single-visit diagnosis and treatment sessions are the goal of future theranostics. In this work, a noncovalent PDT cancer drug-gold nanoparticle (Au NP) conjugate system performed a rapid drug release and deep penetration of the drug into tumors within hours. The drug delivery mechanism of the PDT drug through Au NPs into tumors by passive accumulation was investigated via fluorescence imaging, elemental analysis, and histological staining. The pharmacokinetics of the conjugates over a 7-day test period showed rapid drug excretion, as monitored via the fluorescence of the drug in urine. Moreover, the biodistribution of Au NPs in this study period indicated clearance of the NPs from the mice. This study suggests that noncovalent delivery via Au NPs provides an attractive approach for cancer drugs to penetrate deep into the center of tumors.


Assuntos
Antineoplásicos/farmacocinética , Sistemas de Liberação de Medicamentos , Glioma/tratamento farmacológico , Ouro/farmacologia , Nanopartículas Metálicas/química , Fotoquimioterapia , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Feminino , Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacocinética , Glioma/patologia , Ouro/química , Camundongos , Camundongos Nus , Ratos , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Small ; 7(16): 2301-6, 2011 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-21630446

RESUMO

EGF-modified Au NP-Pc 4 conjugates showed 10-fold improved selectivity to the brain tumor compared to untargeted conjugates. The hydrophobic photodynamic therapy drug Pc 4 can be delivered efficiently into glioma brain tumors by EGF peptide-targeted Au NPs. Compared to the untargeted conjugates, EGF-Au NP-Pc 4 conjugates showed 10-fold improved selectivity to the brain tumor. This delivery system holds promise for future delivery of a wider range of hydrophobic therapeutic drugs for the treatment of hard-to-reach cancers.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Fator de Crescimento Epidérmico/farmacocinética , Ouro/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Fotoquimioterapia/métodos , Animais , Linhagem Celular Tumoral , Preparações de Ação Retardada , Fator de Crescimento Epidérmico/química , Receptores ErbB/metabolismo , Glioma/tratamento farmacológico , Glioma/metabolismo , Humanos , Interações Hidrofóbicas e Hidrofílicas , Indóis/administração & dosagem , Indóis/química , Isoindóis , Nanopartículas Metálicas/ultraestrutura , Camundongos , Nanocápsulas/química , Nanocápsulas/ultraestrutura , Nanoconjugados/uso terapêutico , Nanoconjugados/ultraestrutura , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/química , Resultado do Tratamento
3.
J Am Chem Soc ; 130(32): 10643-7, 2008 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-18642918

RESUMO

A highly efficient drug vector for photodynamic therapy (PDT) drug delivery was developed by synthesizing PEGylated gold nanoparticle conjugates, which act as a water-soluble and biocompatible "cage" that allows delivery of a hydrophobic drug to its site of PDT action. The dynamics of drug release in vitro in a two-phase solution system and in vivo in cancer-bearing mice indicates that the process of drug delivery is highly efficient, and passive targeting prefers the tumor site. With the Au NP-Pc 4 conjugates, the drug delivery time required for PDT has been greatly reduced to less than 2 h, compared to 2 days for the free drug.


Assuntos
Sistemas de Liberação de Medicamentos , Ouro/química , Indóis/administração & dosagem , Nanopartículas Metálicas/química , Neoplasias/tratamento farmacológico , Radiossensibilizantes/administração & dosagem , Animais , Indóis/química , Isoindóis , Camundongos , Camundongos Nus , Fotoquimioterapia , Polietilenoglicóis/química , Radiossensibilizantes/química , Oxigênio Singlete/análise , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta
4.
Part Part Syst Charact ; 32(4): 448-457, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25999665

RESUMO

Targeted drug delivery using epidermal growth factor peptide-targeted gold nanoparticles (EGFpep-Au NPs) is investigated as a novel approach for delivery of photodynamic therapy (PDT) agents, specifically Pc 4, to cancer. In vitro studies of PDT show that EGFpep-Au NP-Pc 4 is twofold better at killing tumor cells than free Pc 4 after increasing localization in early endosomes. In vivo studies show that targeting with EGFpep-Au NP-Pc 4 improves accumulation of fluorescence of Pc 4 in subcutaneous tumors by greater than threefold compared with untargeted Au NPs. Targeted drug delivery and treatment success can be imaged via the intrinsic fluorescence of the PDT drug Pc 4. Using Pc 4 fluorescence, it is demonstrated in vivo that EGFpep-Au NP-Pc 4 impacts biodistribution of the NPs by decreasing the initial uptake by the reticuloendothelial system (RES) and by increasing the amount of Au NPs circulating in the blood 4 h after IV injection. Interestingly, in vivo PDT with EGFpep-Au NP-Pc 4 results in interrupted tumor growth when compared with EGFpep-Au NP control mice when selectively activated with light. These data demonstrate that EGFpep-Au NP-Pc 4 utilizes cancer-specific biomarkers to improve drug delivery and therapeutic efficacy over untargeted drug delivery.

5.
Nanomedicine (Lond) ; 8(1): 123-43, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23256496

RESUMO

Brain cancer tumors cause disruption of the selective properties of vascular endothelia, even causing disruptions in the very selective blood-brain barrier, which are collectively referred to as the blood-brain-tumor barrier. Nanoparticles (NPs) have previously shown great promise in taking advantage of this increased vascular permeability in other cancers, which results in increased accumulation in these cancers over time due to the accompanying loss of an effective lymph system. NPs have therefore attracted increased attention for treating brain cancer. While this research is just beginning, there have been many successes demonstrated thus far in both the laboratory and clinical setting. This review serves to present the reader with an overview of NPs for treating brain cancer and to provide an outlook on what may come in the future. For NPs, just like the blood-brain-tumor barrier, the future is wide open.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/terapia , Nanopartículas , Barreira Hematoencefálica , Humanos
6.
Lasers Surg Med ; 39(9): 723-30, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17960753

RESUMO

INTRODUCTION: High-field magnetic resonance imaging (MRI) is an emerging technique that provides a powerful, non-invasive tool for in vivo studies of cancer therapy in animal models. Photodynamic therapy (PDT) is a relatively new treatment modality for prostate cancer, the second leading cause of cancer mortality in American males. The goal of this study was to evaluate the response of human prostate tumor cells growing as xenografts in athymic nude mice to Pc 4-sensitized PDT. MATERIALS AND METHODS: PC-3, a cell line derived from a human prostate malignant tumor, was injected intradermally on the back flanks of athymic nude mice. Two tumors were initiated on each mouse. One was treated and the other served as the control. A second-generation photosensitizing drug Pc 4 (0.6 mg/kg body weight) was delivered to each animal by tail vein injection 48 hours before laser illumination (672 nm, 100 mW/cm(2), 150 J/cm(2)). A dedicated high-field (9.4 T) small-animal MR scanner was used for image acquisitions. A multi-slice multi-echo (MSME) technique, permitting noninvasive in vivo assessment of potential therapeutic effects, was used to measure the T2 values and tumor volumes. Animals were scanned immediately before and after PDT and 24 hours after PDT. T2 values were computed and analyzed for the tumor regions. RESULTS: For the treated tumors, the T2 values significantly increased (P<0.002) 24 hours after PDT (68.2+/- 8.5 milliseconds), compared to the pre-PDT values (55.8+/-6.6 milliseconds). For the control tumors, there was no significant difference (P = 0.53) between the pre-PDT (52.5+/-6.1 milliseconds) and 24-hour post-PDT (54.3+/-6.4 milliseconds) values. Histologic analysis showed that PDT-treated tumors demonstrated necrosis and inflammation that was not seen in the control. DISCUSSION: Changes in tumor T2 values measured by multi-slice multi-echo MR imaging provide an assay that could be useful for clinical monitoring of photodynamic therapy of prostate tumors.


Assuntos
Indóis/uso terapêutico , Imageamento por Ressonância Magnética/métodos , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Animais , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Camundongos , Camundongos Nus , Transplante Heterólogo
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