Self‐Assembled Autophagy‐Inducing Polymeric Nanoparticles for Breast Cancer Interference In‐Vivo

Wang, Yi; Lin, Yao‐Xin; Qiao, Zeng‐Ying; An, Hong‐Wei; Qiao, Sheng‐Lin; Wang, Lei; Rajapaksha, R.P. Yeshan J.; Wang, Hao

doi:10.1002/adma.201405926

Cited by 119 publications

(98 citation statements)

References 71 publications

(30 reference statements)

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“…Activation of cell death mechanisms in cells presenting enhanced formation of autophagosomes is observed upon treatment with a variety of nanomaterials, including polymeric nanoparticles [52 ] and iron oxide nanoparticles [35]. The observation that several autophagy and apoptosis genes are co-regulated also supports this notion [53].…”

Section: Blockage Of Autophagic Fluxmentioning

confidence: 97%

Differential autophagic responses to nano-sized materials

Popp

Segatori

2015

Current Opinion in Biotechnology

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Autophagy is a complex catabolic pathway that mediates degradation of excess or unwanted cytoplasmic components through the lysosome. Activated by environmental factors, such as nutrient depletion, and intracellular stimuli, such as proteotoxic stress, it provides a highly dynamic quality control mechanism to recycle cellular components, eliminate aberrant materials, and, ultimately, maintain cellular homeostasis. A growing body of evidence suggests that autophagy is also activated upon internalization of engineered nanomaterials, most likely as a protective response to what is perceived as foreign or toxic. This review describes the mechanisms of autophagy activation in response to naturally occurring and engineered nanomaterials. We provide a comprehensive analysis of the impact of nanomaterials on the lysosome-autophagy system, with particular emphasis on cellular markers associated with biocompatible and bioadverse outcomes of autophagy activation, such as clearance of toxic material and autophagy-associated cell death. Potential applications of the next-generation nanomaterials designed to interface with cellular clearance mechanisms with precisely tunable properties are also discussed.

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Section: Blockage Of Autophagic Fluxmentioning

confidence: 97%

Differential autophagic responses to nano-sized materials

Popp

Segatori

2015

Current Opinion in Biotechnology

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“…[16][17][18][19] Generally, these NPs possessed a core-shell morphology which is characterized by an inner hydrophobic core surrounded by a highly water bound, hydrophilic corona. [16][17][18][19] Generally, these NPs possessed a core-shell morphology which is characterized by an inner hydrophobic core surrounded by a highly water bound, hydrophilic corona.…”

Section: Introductionmentioning

confidence: 99%

Preparation and evaluation of PCL–PEG–PCL polymeric nanoparticles for doxorubicin delivery against breast cancer

et al. 2016

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Doxorubicin (DOX), an anthracycline anticancer drug, was successfully incorporated into the polymeric nanoparticles (NPs) based on poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL) amphiphilic triblock copolymers by thin-film hydration and ultrasonic dispersion method. The prepared DOX-loaded polymeric NPs showed spherical shapes with apparent core-shell morphology. The average particle size of DOX-loaded NPs was 130.8 nm with a narrow size distribution (PDI = 0.200). DOX was entrapped in the polymeric NPs with encapsulation efficiency and loading content of 86.71 ± 2.05% and 8.72 ± 0.57%, respectively. DOX-release from the NPs was in a sustained and long-term fashion up to several weeks, and achieved faster release at pH5.5 than that at pH7.0. In vitro cytotoxicity assay against EMT6 cells demonstrated that the cytotoxic effect of DOX-loaded NPs gradually approached that of free DOX as increasing the concentration and the incubation time. Confocal laser scanning microscopy results showed that the DOX fluorescence was distributed both in cytoplasm and nucleus for DOX-loaded NPs treated cells, while the red fluorescence was observed mostly in the nucleus for free DOX treated cells. In cell analyzer was used to further quantitatively analyze the intracellular distribution of DOX-loaded NPs on a cell-by-cell basis, indicating that the DOX fluorescence in nucleus was lower than that in cytoplasm for 1 h incubation, but higher than that in cytoplasm for long-time incubation (4 h and 24 h). Furthermore, ex vivo DOX fluorescence imaging revealed that DOX-loaded NPs had highly efficient targeting and accumulation at the implanted site of EMT6 xenograft tumor in vivo through an enhanced permeation and retention mechanism. These results suggested that the DOX-loaded polymeric NPs based on PCL-PEG-PCL triblock copolymer would be a promising nanosized drug delivery system for cancer therapy. successfully prepared by thin-film hydration and ultrasonic dispersion method. The obtained NPs exhibited apparent core-shell morphology with satisfactory size (130 nm), which was favorable for intravenous injection. Ex vivo DOX fluorescence imaging revealed that DOX-loaded NPs had highly efficient targeting and accumulation at the implanted site of EMT6 xenograft tumor in vivo through an enhanced permeation and retention mechanism. The prepared DOX-loaded polymeric NPs would be a promising nanosized drug delivery system for cancer therapy.

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“…26,27 Nanoparticles induce oxidative stress and autophagy. 26,30,31 In this study, the ND particles located in lysosomes did not disrupt mitotic progression and cytokinesis (Fig. 6A).…”

Section: Ub-coated Nds Bind To Autophagy Receptors On Bacteriamentioning

confidence: 46%

“…28,29 Nanoparticles induce oxidative stress and autophagy; 26,30 the polymer-conjugated BECN1 nanoparticle can enhance the induction of autophagy. 31 Furthermore, nanoparticles can induce cellular protective autophagy. 32 Hence, delineating the precise mechanisms of autophagy pathways is crucial to facilitate the biomedical applications of nanomaterials.…”

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confidence: 99%

Ubiquitin-coated nanodiamonds bind to autophagy receptors for entry into the selective autophagy pathway

et al. 2017

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Selective macroautophagy/autophagy plays a pivotal role in the processing of foreign pathogens and cellular components to maintain homeostasis in human cells. To date, numerous studies have demonstrated the uptake of nanoparticles by cells, but their intracellular processing through selective autophagy remains unclear. Here we show that carbon-based nanodiamonds (NDs) coated with ubiquitin (Ub) bind to autophagy receptors (SQSTM1 [sequestosome 1], OPTN [optineurin], and CALCOCO2/NDP52 [calcium binding and coiled-coil domain 2]) and are then linked to MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3) for entry into the selective autophagy pathway. NDs are ultimately delivered to lysosomes. Ectopically expressed SQSTM1-green fluorescence protein (GFP) could bind to the Ub-coated NDs. By contrast, the Ub-associated domain mutant of SQSTM1 (DUBA)-GFP did not bind to the Ub-coated NDs. Chloroquine, an autophagy inhibitor, prevented the ND-containing autophagosomes from fusing with lysosomes. Furthermore, autophagy receptors OPTN and CALCOCO2/NDP52, involved in the processing of bacteria, were found to be involved in the selective autophagy of NDs. However, ND particles located in the lysosomes of cells did not induce mitotic blockage, senescence, or cell death. Single ND clusters in the lysosomes of cells were observed in the xenografted human lung tumors of nude mice. This study demonstrated for the first time that Ub-coated nanoparticles bind to autophagy receptors for entry into the selective autophagy pathway, facilitating their delivery to lysosomes.

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Self‐Assembled Autophagy‐Inducing Polymeric Nanoparticles for Breast Cancer Interference In‐Vivo

Cited by 119 publications

References 71 publications

Differential autophagic responses to nano-sized materials

Differential autophagic responses to nano-sized materials

Preparation and evaluation of PCL–PEG–PCL polymeric nanoparticles for doxorubicin delivery against breast cancer

Ubiquitin-coated nanodiamonds bind to autophagy receptors for entry into the selective autophagy pathway

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