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1.
Nat Mater ; 10(3): 243-51, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21336265

RESUMO

Vaccines based on recombinant proteins avoid the toxicity and antivector immunity associated with live vaccine (for example, viral) vectors, but their immunogenicity is poor, particularly for CD8(+) T-cell responses. Synthetic particles carrying antigens and adjuvant molecules have been developed to enhance subunit vaccines, but in general these materials have failed to elicit CD8(+) T-cell responses comparable to those for live vectors in preclinical animal models. Here, we describe interbilayer-crosslinked multilamellar vesicles formed by crosslinking headgroups of adjacent lipid bilayers within multilamellar vesicles. Interbilayer-crosslinked vesicles stably entrapped protein antigens in the vesicle core and lipid-based immunostimulatory molecules in the vesicle walls under extracellular conditions, but exhibited rapid release in the presence of endolysosomal lipases. We found that these antigen/adjuvant-carrying vesicles form an extremely potent whole-protein vaccine, eliciting endogenous T-cell and antibody responses comparable to those for the strongest vaccine vectors. These materials should enable a range of subunit vaccines and provide new possibilities for therapeutic protein delivery.


Assuntos
Imunidade Celular , Imunidade Humoral , Lipossomos/química , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologia , Adjuvantes Imunológicos/química , Animais , Portadores de Fármacos , Desenho de Fármacos , Memória Imunológica , Bicamadas Lipídicas/química , Lipossomos/imunologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Ovalbumina/imunologia , Vacinas Sintéticas/química , Vacinas Virais/química , Vacinas Virais/imunologia
2.
Nanotechnology ; 22(15): 155605, 2011 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-21389566

RESUMO

A critical issue for current liposomal carriers in clinical applications is their leakage of the encapsulated drugs that are cytotoxic to non-target tissues. We have developed partially polymerized liposomes composed of polydiacetylene lipids and saturated lipids. Cross-linking of the diacetylene lipids prevents the drug leakage even at 40 °C for days. These inactivated drug carriers are non-cytotoxic. Significantly, more than 70% of the encapsulated drug can be instantaneously released by a laser that matches the plasmon resonance of the tethered gold nanoparticles on the liposomes, and the therapeutic effect was observed in cancer cells. The remote activation feature of this novel drug delivery system allows for precise temporal and spatial control of drug release.


Assuntos
Preparações de Ação Retardada/química , Lipossomos/química , Nanopartículas Metálicas/química , 1,2-Dipalmitoilfosfatidilcolina/química , Compostos de Anilina , Disponibilidade Biológica , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Microscopia Crioeletrônica , Preparações de Ação Retardada/síntese química , Preparações de Ação Retardada/efeitos da radiação , Di-Inos/química , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Estabilidade de Medicamentos , Endocitose , Feminino , Fluoresceínas/administração & dosagem , Fluoresceínas/farmacocinética , Glicina , Ouro/química , Humanos , Iminoácidos/administração & dosagem , Iminoácidos/farmacocinética , Lasers , Lipossomos/síntese química , Lipossomos/efeitos da radiação , Lisofosfolipídeos/química , Nanopartículas Metálicas/efeitos da radiação , Compostos de Organotecnécio/administração & dosagem , Compostos de Organotecnécio/farmacocinética , Tamanho da Partícula , Fosfatidilcolinas/química , Fosfatidiletanolaminas/química , Polímeros/síntese química , Polímeros/química , Ressonância de Plasmônio de Superfície
3.
Can J Plast Surg ; 21(4): 226-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24497763

RESUMO

Reduction mammoplasty is one of the most commonly performed procedures in plastic surgery. Occasionally, there are findings reported by pathologists that are unfamiliar to the treating surgeon. The aim of the present study was to determine the types of pathologies encountered in reduction mammoplasty specimens. From this list of diagnoses, a best practice guideline for management will be organized to better assist plastic surgeons in the management of patients with incidental findings on pathology reports. A total of 441 pathology reports from patients who underwent bilateral or unilateral reduction mammoplasty in the past three years were identified. A list of 21 different pathologies was generated from the pathology reports, along with supplemental data from recent texts and articles. Occult carcinomas were encountered in two cases (0.45%) and high-risk lesions were found in three cases (0.68%) at the authors' institution. An algorithm was then constructed to organize the pathologies according to risk of malignancy and assign them to a management guideline. There are many different lesions encountered incidentally in reduction mammoplasty specimens that may or may not confer some cancer risk. It is important for plastic surgeons to know which lesions need closer follow-up to provide the best care for their patients.


Les réductions mammaires font partie des interventions les plus exécutées en chirurgie plastique. Il arrive que le médecin traitant ne soit pas familier avec les observations du pathologiste. La présente étude visait à déterminer le type de pathologies observées dans des prélèvements de réductions mammaires. À partir de cette liste de diagnostics, des directives de pratiques exemplaires de prise en charge sont exposées pour mieux aider le plasticien à prendre en charge les patients présentant des observations fortuites dans le rapport de pathologie. Au total, les chercheurs ont trouvé 441 rapports de pathologie de patients qui ont subi une réduction mammaire bilatérale ou unilatérale depuis trois ans. Ils ont dressé une liste de 21 pathologies différentes à partir des rapports de pathologie, de même que d'autres, tirées de textes et articles récents. Dans l'établissement des auteurs, on a observé deux cas de carcinomes occultes (0,45 %) et trois cas de lésions à haut risque (0,68 %). Un algorithme a ensuite été construit pour classer les pathologies d'après le risque de malignité et leur accoler une directive de prise en charge. Il existe de nombreuses lésions observées fortuitement dans les échantillons de réductions mammaires qui peuvent ou non s'associer à un risque de cancer. Il est important pour le plasticien de savoir quelles lésions doivent faire l'objet d'un suivi plus étroit pour dispenser les meilleurs soins aux patients.

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