Intracellular transport of nanocarriers across the intestinal epithelium

Fan, Weiwei; Xia, Dengning; Zhu, Quanlei; Hu, Lei; Gan, Yong

doi:10.1016/j.drudis.2016.04.007

Cited by 61 publications

(40 citation statements)

References 68 publications

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“…26 In general, NPs merge with early endosomes firstly, mature into late endosomes, and fuse with lysosomes ultimately, a limiting step for NPs to exert pharmacological actions. 27 Since NPs are prone to be degraded in lysosomes due to abundant hydrolytic enzymes, lysosome becomes the endpoint for most nanocarriers which cannot be transported further. 28 In this study, the colocalization of PLGA NPs with lysosomes made us envision that endocytosed NPs could be transported from early endosomes to lysosomes via the early endosome/late endosome/lysosome pathway.…”

mentioning

confidence: 99%

Understanding the translocation mechanism of PLGA nanoparticles across round window membrane into the inner ear: a guideline for inner ear drug delivery based on nanomedicine

Zhang¹,

Xu²,

Cao³

et al. 2018

IJN

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Background The round window membrane (RWM) functions as the primary biological barrier for therapeutic agents in the inner ear via local application. Previous studies on inner ear nano-drug delivery systems mostly focused on their pharmacokinetics and distribution in the inner ear, but seldom on the interaction with the RWM. Clarifying the transport mechanism of nanoparticulate carriers across RWM will shed more light on the optimum design of nano-drug delivery systems intended for meeting demands for their clinical application. Methods The poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) encapsulating coumarin-6 were prepared by emulsifying solvent evaporation method. We utilized confocal laser scanning microscope (CLSM) in combination with transmission electron microscope to investigate the transport pathway of PLGA NPs in the RWM. Simultaneously, the concentration and time dependence of NPs across the RWM were also determined. The endocytic mechanism of NPs through this membrane interface was classically analyzed by means of various endocytic inhibitors. The intracellular location of NPs into lysosomes was evaluated using CLSM scanning microscope colocalization analysis. The Golgi-related inhibitors were employed to probe into the function of Golgi and endoplasmic reticulum (ER) in the discharge of NPs out of cells. Results PLGA NPs were herein transported through the RWM of a sandwich-like structure into the perilymph via the transcellular pathway. NPs were internalized predominantly via macropinocytosis and caveolin-mediated endocytic pathways. After being internalized, the endocytosed cargos were entrapped within the lysosomal compartments and/or the endoplasmic reticulum/Golgi apparatus which mediated the exocytotic release of NPs. Conclusion For the first time, we showed the translocation itinerary of NPs in RWM, providing a guideline for the rational fabrication of inner ear nanoparticulate carriers with better therapeutic effects.

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confidence: 99%

Understanding the translocation mechanism of PLGA nanoparticles across round window membrane into the inner ear: a guideline for inner ear drug delivery based on nanomedicine

Zhang¹,

Xu²,

Cao³

et al. 2018

IJN

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“…In addition, highly efficient intracellular trafficking is significant to the transepithelial absorption of NPs. However, orally administered NPs always have the “easy uptake and hard transcytosis” problem . It was reported that most orally administrated NPs could not be efficiently transported across the epithelium and enter the circulation, which resulted in poor bioavailability of the encapsulated drugs .…”

Section: Methodsmentioning

confidence: 99%

A Probiotic Spore‐Based Oral Autonomous Nanoparticles Generator for Cancer Therapy

Song¹,

Zheng²,

Jia³

et al. 2019

Advanced Materials

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Spores, the dormant life forms of probiotics, can germinate to metabolically active vegetative cells with the disintegration of their hydrophobic protein coat in the intestinal microenvironment, which provides the possibility for the formation of nanoparticles (NPs) in vivo. Inspired by the natural physiological process of spores, herein, an oral autonomous NPs generator is developed to overcome the spatially variable gastrointestinal tract environment and multibiological barriers. Spores modified with deoxycholic acid (DA) and loaded with chemotherapeutic drugs (doxorubicin and sorafenib, DOX/SOR) serve as an autonomous production line of NPs, which can efficaciously protect the drugs passing through the rugged environment of the stomach and furthermore can be transported to the intestinal environment and colonized rapidly. Subsequently, the DOX/SOR/Spore‐DA NPs are produced by the autonomous NPs generator in the intestinal regions based on the disintegrated hydrophobic protein and the hydrophilic DA, and they can efficiently penetrate the epithelial cells via the bile acid pathway, increasing basolateral drug release. In vitro and in vivo studies confirm that this biological nanogenerator can autonomously produce substantial NPs in the intestine, providing a promising strategy for cancer therapy.

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“…receptors, which are targeted by the Golgi complex [149]. ER and Golgi complexs are important for both secretory and endocytic pathways, and are also an option to escape the acidic lysosomal environment [12]. Yu and colleagues found a trafficking pathway between the ER and plasmatic membrane (PM), and then from the PM to ER via the Golgi complex.…”

Section: Nonendocytic Route As An Alternativementioning

confidence: 99%

“…However, endosomes and lysosomes, which have a low pH and are rich in enzymes, can result in drug degradation or nonspecific distribution [10,11]. Thus, modulation of the size, charge, and surface composition of a nanomaterial can dictate the internalization pathway, enabling the nanomaterial to evade lysosomes and interact with its target organelle [12]. Indeed, the potential of nanomaterials to overcome such barriers has led to the development of platforms capable of improving their bioavailability [13].…”

Section: Introductionmentioning

confidence: 99%

Strategies for the enhanced intracellular delivery of nanomaterials

Azevedo

Macedo

Sarmento

2018

Drug Discovery Today

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The intracellular delivery of nanomaterials and drugs has been attracting increasing research interest, mainly because of their important effects and functions in several organelles. Targeting specific organelles can help treat or decrease the symptoms of diabetes, cancer, infectious, and autoimmune diseases. Tuning biological and chemical properties enables the creation of functionalized nanomaterials with enhanced intracellular uptake, ability to escape premature lysosome degradation, and to reach a specific target. Here, we provide an update of recent advances in the intracellular delivery mechanisms that could help drugs reach their target more efficiently.

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Intracellular transport of nanocarriers across the intestinal epithelium

Cited by 61 publications

References 68 publications

Understanding the translocation mechanism of PLGA nanoparticles across round window membrane into the inner ear: a guideline for inner ear drug delivery based on nanomedicine

Understanding the translocation mechanism of PLGA nanoparticles across round window membrane into the inner ear: a guideline for inner ear drug delivery based on nanomedicine

A Probiotic Spore‐Based Oral Autonomous Nanoparticles Generator for Cancer Therapy

Strategies for the enhanced intracellular delivery of nanomaterials

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