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1.
Adv Healthc Mater ; 6(21)2017 Nov.
Article in English | MEDLINE | ID: mdl-28777501

ABSTRACT

Direct labeling of human mesenchymal stem cells (hMSC) prior to transplantation provides a means to track cells after administration and it is a powerful tool for the assessment of new cell-based therapies. Biocompatible nanoprobes consisting of liposome-indocyanine green hybrid vesicles (liposome-ICG) are used to safely label hMSC. Labeled hMSC recapitulating a 3D cellular environment is transplanted as spheroids subcutaneously and intracranially in athymic nude mice. Cells emit a strong NIR signal used for tracking post-transplantation with the IVIS imaging system up to 2 weeks (subcutaneous) and 1 week (intracranial). The transplanted stem cells are imaged in situ after engraftment deep in the brain up to 1 week in living animals using optical imaging techniques and without the need to genetically modify the cells. This method is proposed for efficient, nontoxic direct cell labeling for the preclinical assessment of cell-based therapies and the design of clinical trials, and potentially for localization of the cell engraftment after transplantation into patients.


Subject(s)
Cell Tracking/methods , Indocyanine Green/chemistry , Liposomes/chemistry , Mesenchymal Stem Cell Transplantation , Nanostructures/chemistry , A549 Cells , Adult , Animals , Bone Marrow Cells/cytology , Brain/diagnostic imaging , Brain/pathology , Cell Survival/drug effects , Cells, Cultured , Female , HT29 Cells , Humans , Male , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Mice , Mice, Nude , Microscopy, Confocal , Nanostructures/toxicity , Optical Imaging , Transplantation, Heterologous , Young Adult
2.
Einstein (Sao Paulo) ; 14(1): 99-103, 2016.
Article in English, Portuguese | MEDLINE | ID: mdl-27074238

ABSTRACT

The use of nanocarriers as drug delivery systems for therapeutic or imaging agents can improve the pharmacological properties of commonly used compounds in cancer diagnosis and treatment. Advances in the surface engineering of nanoparticles to accommodate targeting ligands turned nanocarriers attractive candidates for future work involving targeted drug delivery. Although not targeted, several nanocarriers have been approved for clinical use and they are currently used to treat and/or diagnosis various types of cancers. Furthermore, there are several formulations, which are now in various stages of clinical trials. This review examined some approved formulations and discussed the advantages of using nanocarriers in cancer therapy.


Subject(s)
Antineoplastic Agents/therapeutic use , Drug Carriers/therapeutic use , Nanoparticles/therapeutic use , Neoplasms/diagnosis , Neoplasms/drug therapy , Doxorubicin/analogs & derivatives , Doxorubicin/therapeutic use , Humans , Polyethylene Glycols/therapeutic use
3.
Einstein (Säo Paulo) ; 14(1): 99-103, Jan.-Mar. 2016. tab, graf
Article in English | LILACS | ID: lil-778486

ABSTRACT

ABSTRACT The use of nanocarriers as drug delivery systems for therapeutic or imaging agents can improve the pharmacological properties of commonly used compounds in cancer diagnosis and treatment. Advances in the surface engineering of nanoparticles to accommodate targeting ligands turned nanocarriers attractive candidates for future work involving targeted drug delivery. Although not targeted, several nanocarriers have been approved for clinical use and they are currently used to treat and/or diagnosis various types of cancers. Furthermore, there are several formulations, which are now in various stages of clinical trials. This review examined some approved formulations and discussed the advantages of using nanocarriers in cancer therapy.


RESUMO A utilização de nanocarreadores como sistemas de entrega de drogas para agentes terapêuticos ou de imagem pode aumentar as propriedades farmacológicas dos compostos normalmente utilizados no tratamento e diagnóstico de câncer. Avanços em engenharia de superfície de nanopartículas para a acomodação de ligantes alvo têm feito dos nanocarreadores candidatos atrativos para um futuro trabalho envolvendo entrega de droga direcionada. Embora não direcionados, muitos nanocarreadores terapêuticos foram aprovados para uso clínico no tratamento e/ou diagnóstico de vários tipos de câncer. Além disso, há várias outras formulações que se encontram agora em estágio de testes clínicos. Este artigo de revisão examinou algumas formulações aprovadas e discutiu as vantagens da utilização de nanocarreadores na terapia de câncer.


Subject(s)
Humans , Drug Carriers/therapeutic use , Nanoparticles/therapeutic use , Neoplasms/diagnosis , Neoplasms/drug therapy , Antineoplastic Agents/therapeutic use , Polyethylene Glycols/therapeutic use , Doxorubicin/analogs & derivatives , Doxorubicin/therapeutic use
4.
Free Radic Biol Med ; 90: 91-100, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26577174

ABSTRACT

Chloroquine (CQ), a quinolone derivative widely used to treat and prevent malaria, has been shown to exert a potent adjuvant effect when combined with conventional glioblastoma therapy. Despite inducing lysosome destabilization and activating p53 in human glioma cells, the mechanisms underlying cell death induced by this drug are poorly understood. Here, we analyzed in a time- and dose-dependent manner, the effects of CQ upon mitochondria integrity, autophagy regulation and redox processes in four human glioma cell lines that differ in their resistance to this drug. NAC-containing media protected cells against CQ-induced loss of mitochondrial membrane potential (MMP), autophagic vacuoles (LC3II) accumulation and loss of cell viability induced by CQ. However, we noticed that part of this protection was due to media acidification in NAC preparations, alerting for problems in experimental procedures using NAC. The results indicate that although CQ induces accumulation of LC3II, mitochondria, and oxidative stress, neither of these events is clearly correlated to cell death induced by this drug. The only event elicited in all cell lines at equitoxic doses of CQ was the loss of MMP, indicating that mitochondrial stability is important for cells resistance to this drug. Finally, the data indicate that higher steady-state MMP values can predict cell resistance to CQ treatment.


Subject(s)
Chloroquine/pharmacology , Glioma/drug therapy , Membrane Potential, Mitochondrial/drug effects , Oxidative Stress/drug effects , Acetylcysteine/pharmacology , Cell Death/drug effects , Cell Line, Tumor , Glioma/metabolism , Glioma/pathology , Humans , Reactive Oxygen Species/metabolism
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