Nanocarriers’ entry into the cell: relevance to drug delivery

Hillaireau, Hervé; Couvreur, Patrick

doi:10.1007/s00018-009-0053-z

Cited by 1,341 publications

(1,060 citation statements)

References 210 publications

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“…During the process of cellular uptake, the exogenous particles are initially enclosed into endosomes, which mature into multivesicular bodies or late endosomes and eventually fuse with lysosomes [34]. Mitochondria are important intracellular energy metabolism places, and are closely related to the signals which induce cell apoptosis.…”

Section: Intracellular Distributionmentioning

confidence: 99%

Preparation and cellular uptake of PLGA particles loaded with lamivudine

et al. 2012

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Poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles loaded with lamivudine and coated with bovine serum albumin (BSA) were prepared via a double emulsion method. The influences of experiments parameters such as volume of inner aqueous phase, concentration of organic phase and ultrasonication time on the particle size and drug entrapment efficiency were investigated, obtaining PLGA particles with a diameter of ~260 nm and drug entrapment efficiency of ~35%. The particles were observed by scanning electron microscopy and transmittance electron microscopy, showing a core-shell structure. BCA assay found that 58 mg BSA was present on/in 1 g LPB particles. The loaded lamivudine showed a burst release at beginning and sustained release until 24 h in physiological conditions. Low pH could accelerate the release of lamivudine from PLGA particles, making the PLGA particles potential intelligent intracellular drug carriers. The PLGA particles were readily internalized into the human liver cells within a short time and increased gradually with the prolongation of incubation time regardless of the loading of lamivudine. The particles either resided within lysosomes or transferred to cytoplasm, but could not enter into the cell nucleus. The cell viability was not significantly influenced in the presence of the particles regardless of lamivudine encapsulation, suggesting that this kind of particles may be a good candidate for the intracellular anti-hepatitis B drug delivery.PLGA, lamivudine, cell uptake, intracellular distribution, drug delivery Citation:Wang B, Chen G Q, Mao Z W, et al. Preparation and cellular uptake of PLGA particles loaded with lamivudine.

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Section: Intracellular Distributionmentioning

confidence: 99%

Preparation and cellular uptake of PLGA particles loaded with lamivudine

et al. 2012

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“…Several pathways have been considered to mediate the process in uptake of GNP, such as clathrin-mediated endocytosis, caveolae-mediated endocytosis, macropinocytosis, phagocytosis, and direct penetration. [16][17] Generally speaking, these processes can be classified as specific (via receptor-ligand interaction) or non-specific ways. It is feasible to conjugate specific ligands to the surface of GNPs.…”

Section: The Cellular Uptake Processmentioning

confidence: 99%

Cellular Uptake, Intracellular Trafficking and Biological Responses of Gold Nanoparticles

Jiang

Wang

Chen

2011

J Chinese Chemical Soc

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Promising application of gold nanoparticles (GNPs) in biomedical and environmental fields is increasing the likelihood of direct interaction with living systems. The knowledge about GNPs interacting with cells is quite limited and however, is necessary for risk prediction and evaluation of biological effects. Herein, we review recent advances in cellular effects of GNPs including cellular uptake, trafficking, subcellular distribution and cellular responses, and the relationship between physiochemical properties of GNPs and biological effects as well. To uncover these issues, it is quite instructive for safe and sustainable use of GNPs.

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“…Possible mechanisms include, among others, pinocytosis, non-specific endocytosis and receptor-mediated endocytosis. [287][288] Especially receptor-mediated uptake is a widely investigated approach to targeting of specific cell types. [289][290] Since most types of carcinogenic cells are characterized by an increased expression of folate receptors, functionalization of nanometric delivery systems with folic acid on the surface results in an enhanced uptake of the respective vehicles in carcinogenic cells rather than in healthy cells.…”

Section: P(hema-co-maa) Microgels: Fluorescent Labeling and Cell Testsmentioning

confidence: 99%

Light-Sensitive Polymeric Nanoparticles Based on Photo-Cleavable Chromophores

Klinger

2013

Springer Theses

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This thesis focuses on the design, synthesis and characterization of novel photo-sensitive microgels and nanoparticles as potential materials for the loading and light-triggered release/accessibility of functional compounds. In order to realize this concept, different approaches to irradiation-dependent response mechanisms have been investigated.Novel light-cleavable divinyl functionalized monomeric crosslinkers based on o-nitrobenzyl derivatives were synthesized and used for the preparation of either PMMA or hydroxyl functionalized PHEMA microgels swellable and degradable in organic solvents. By the introduction of anionic MAA moieties into the PHEMA microgels, this concept was successfully transferred to double stimuli-responsive p(HEMA-co-MAA) hydrogel nanoparticles exhibiting a pH-dependent swelling and light-induced degradation behavior in aqueous media. This sensitivity to two orthogonal triggers is proposed to combine a pHinduced post-formation loading mechanism with a pH-and light-triggered release. In addition, a new class of enzyme-and light-sensitive PAAm microgels based on (meth-)acrylate functionalized dextrans as photo-and enzymatically degradable macromolecular crosslinkers was developed by introducing a photo-labile linker between the enzymatically degradable dextran chain and the polymerizable vinyl moieties. Here, the water solubility of the crosslinkers is assumed to enable an in situ loading approach of hydrophilic compounds.A different approach to the loading of microgels is based on photo-labile covalent microgel-drug conjugates. The first step to the realization of this concept was achieved by the development of a novel functional monomer consisting of a doxorubicin molecule covalently attached to a radically polymerizable methacrylate group via a photo-cleavable linker.Moreover, in order to enable the release of hydrophobic substances in aqueous media, hydrophobic nanoparticles consisting of a photo-resist polymer were designed to be degradable upon irradiation in water. Light-triggered conversion of the initial hydrophobic polymer into hydrophilic PMAA induced in situ particle dissolution and release of nile red.Since the introduction of a stimuli-responsive shell around a microgel is assumed to prevent leakage of embedded compounds, studies on non-stimuli-responsive shell formation around preformed microgel seed particles and the formation of microgel cores in polymeric shells were conducted to investigate potential synthetic pathways to this approach.In a last attempt, the surface of PHEMA and p(HEMA-co-MAA) microgels was functionalized with cinnamoyl groups in order to trigger the (reversible) particles interaction with each other by light-induced [2+2] cycloaddition reactions.

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Nanocarriers’ entry into the cell: relevance to drug delivery

Cited by 1,341 publications

References 210 publications

Preparation and cellular uptake of PLGA particles loaded with lamivudine

Preparation and cellular uptake of PLGA particles loaded with lamivudine

Cellular Uptake, Intracellular Trafficking and Biological Responses of Gold Nanoparticles

Light-Sensitive Polymeric Nanoparticles Based on Photo-Cleavable Chromophores

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