Intracellular trafficking pathways and drug delivery: fluorescence imaging of living and fixed cells

Watson, Peter

doi:10.1016/j.addr.2004.05.003

Cited by 251 publications

(176 citation statements)

References 155 publications

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“…Such binding proteins are assumed to travel together with transporter ligands along cytoskeletal tracks to their distinctive membrane sites (Bilej and Vetvicka 1989). Modern reflexions consider also endocytic trafficking pathways as important routes of drugs in the cell (Watson et al 2005). For example, some weakly basic drugs such as doxorubicin may accumulate within acidic lysosomal organelles (Weaver et al 1991), and thus may follow the traffic via vesicular pathways either in the lysosomal compartment (Lloyd 2000) or after fusion with endosomes in the multivesicular body (MVB) compartment.…”

Section: An Extended Phase Conceptmentioning

confidence: 99%

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Drug transporters in pharmacokinetics

Petzinger¹,

Geyer²

2006

Naunyn Schmied Arch Pharmacol

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This review deals with the drug transporters allowing drugs to enter and leave cells by carrier-mediated pathways. Emphasis is put on liver transporters but systems in gut, kidney, and blood-brain barrier are mentioned as well. Drug-drug interactions on carriers may provoke significant modification in pharmacokinetics as do carrier gene polymorphisms yielding functional carrier protein mutations. An integrated phase concept should reflect the interplay between drug metabolism and drug transport.

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Section: An Extended Phase Conceptmentioning

confidence: 99%

“…3) (Rost et al 1999). New approaches use fluorescent drugs or drugs coupled to fluorescent dyes for live cell imaging of intracellular transport pathways (Watson et al 2005). This will better help to elucidate phase 3 drug transport in the future.…”

Section: An Extended Phase Conceptmentioning

confidence: 99%

Drug transporters in pharmacokinetics

Petzinger¹,

Geyer²

2006

Naunyn Schmied Arch Pharmacol

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“…-The interactions between nano-sized objects, nanoparticles, and living organisms is currently under intense study [1][2][3][4][5][6][7][8][9][10][11][12]. The nanoscale is privileged because many endogenous biological processes (for example, internalisation and trafficking of cargoes in cells [13]) operate on the scale of tens of nanometres. Engineered nanoparticles can thereby engage with biological processes in fundamentally new manners [2][3][4]14].…”

mentioning

confidence: 99%

Theoretical framework for nanoparticle uptake and accumulation kinetics in dividing cell populations

Åberg¹,

Kim²,

Salvati³

et al. 2013

EPL

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-Nano-sized objects interact with biological systems in fundamentally novel ways, thereby holding great promise for targeted drug-delivery. It has also been suggested they could constitute a hitherto unseen hazard. Numerous experimental studies in the field are taking place. We consider that the nature of the interactions allows a more fundamental theoretical framework to be developed. In particular, we describe the intimate link that develops between nanoparticle uptake and cell population evolution. Explicit analytical results are given and the theory compared to experimental observations.

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“…Por isso nos últimos anos as técnicas para imageamento nessa área têm evoluído e criado uma expectativa de melhor compreensão desse processo. 83 Essas técnicas permitem observação direta de nanopartículas individuais no interior das cé-lulas e oferecem avanços significativos na resolução espacial (10-20 nm) e temporal (1-2 s) para imagens subcelulares. 84 Por isso, para os próximos anos, com o desenvolvimento e custos mais acessíveis dessas ferramentas espera-se elucidar melhor esses eventos, o que certamente auxiliaria no entendimento do processo de interação nanopartículas-células.…”

Section: Figura 2 Local De Atuação De Inibidores De Endocitose Nas Vunclassified

“…A evolução e aplicação de técnicas para imageamento têm contribuído para investigação desses fenômenos possibilitando melhor entendimento dos mesmos. 83 Essas técnicas permitem observação direta de nanopartículas individuais no interior de células e de organelas intracelulares, proporcionando avanços significativos na resolução espacial (10-20nm) e temporal (1-2 s) de imagens subcelulares. 84 A utilização de nanopartículas já é uma realidade crescente a cada dia nas mais diversas áreas.…”

Section: Conclusãounclassified

Como estudar interações entre nanopartículas e sistemas biológicos

et al. 2016

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Recebido em 02/05/2016; aceito em 15/06/2016; publicado na web em 16/08/2016 STUDYING THE INTERACTIONS BETWEEN NANOPARTICLES AND BIOLOGICAL SYSTEMS. Although in recent years there has been an increasing amount of literature on nanotechnology and their clinical applications, it is still scarce a deep understanding of the interactions at the molecular levels between nanoparticles and cells. Studies demonstrating the underlying mechanisms of nanoparticles endocytosis, intracellular trafficking, and cellular processing are imperative to understand better how cells interact with those materials and their possible undesired effects, e.g. nanotoxicity. The rising awareness concerning nanoparticles applications and its interactions with the cellular environment is part of the new research field called Nanotoxicology. The cumulative knowledge in nanotoxicology will allow us to foresee toxic effects, establish regulations and limits for nanoparticles applications. In this work, we discuss the theoretical concepts about studying endocytosis and intracellular trafficking of nanoparticles. The nanoparticles-cell interactions are a multi-step process, which can be divided into nanoparticles' internalization, intracellular processing and triggering effects of nanomaterials on eukaryotic cells. Finally, we discuss the main techniques used to study this process: flow cytometry, use of endocytosis inhibitors and confocal microscopy.Keywords: endocytosis; intracellular trafficking; nanoparticles, nanotoxicology; nano-cell interactions. INTRODUÇÃONanotecnologia é um dos ramos mais promissores de tecnologia, sobre o qual se deposita grandes expectativas. 1 Somente em 2015, foram publicados cerca de 9400 artigos relacionados ao termo "Nanotechnology" no banco de dados Science Direct; além disso, diversos produtos têm sido testados e comercializados, por exemplo, protetores solares, cosméticos, produtos biomédicos, biosensores e sistemas para transporte e entrega de fármacos. 2 Entretanto, há uma crescente preocupação com a segurança e possíveis efeitos nocivos de nanomateriais que vêm sendo desenvolvidos, 3 pois dados e regulamentações internacionais referentes à segurança e uso desses materiais ainda são escassos, ainda estão em debate ou em fase de implementação. 4 Uma nova área da ciência destinada ao estudo de efeitos adversos de nanomateriais foi recentemente criada, a Nanotoxicologia. 5 O conhecimento acumulado nessa área tem como objetivo prever efeitos tóxicos e auxiliar nas regulamentações e diretrizes para aplicação da nanotecnologia 6 e uso de produtos a ela relacionados. A Figura 1 mostra o crescimento do número de artigos científicos que contêm o termo "nanotoxicology" e estão no banco de dados do National Center for Biotechnology Information (NCBI), subdivisão do National Institute of Health (NIH/USA).Apesar do número de artigos em nanotoxicologia ser crescente, esta é uma área ainda muito recente (com menos de uma década), e ainda não é possível determinar exatamente quais impactos os sistemas naturais e artificiais co...

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Intracellular trafficking pathways and drug delivery: fluorescence imaging of living and fixed cells

Cited by 251 publications

References 155 publications

Drug transporters in pharmacokinetics

Drug transporters in pharmacokinetics

Theoretical framework for nanoparticle uptake and accumulation kinetics in dividing cell populations

Como estudar interações entre nanopartículas e sistemas biológicos

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