Enhancing tumor chemotherapy and overcoming drug resistance through autophagy-mediated intracellular dissolution of zinc oxide nanoparticles

Hu, Yi; Hou-rui, Zhang; Dong, Liang; Xu, Mingxiang; Zhang, Li; Ding, Weiping; Zhang, Jiqian; Lin, Jun; Zhang, Yunjiao; Qiu, Bensheng; Wei, Pengfei; Wen, Longping

doi:10.1039/c8nr08442d

Cited by 70 publications

(39 citation statements)

References 67 publications

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“…The induction of autophagy has also been observed following treatment with different types of nanoparticles, such as silica nanoparticles, silver nanoparticles, and others [50,53]. Autophagy is activated in human cancer cells by zinc oxide nanoparticles, which are currently under development for use in enhancing tumor chemotherapy and overcoming drug resistance [54]. Quantum dots are also currently under development for use in a broad range of biomedical imaging applications and have been shown to induce lysosome-dependent autophagy activation, ROS production, and toxicity in human hepatocytes [55].…”

Section: Autophagy Dysfunction Induced By Nanomaterialsmentioning

confidence: 99%

The Current Understanding of Autophagy in Nanomaterial Toxicity and Its Implementation in Safety Assessment-Related Alternative Testing Strategies

Chen

Liao

et al. 2020

IJMS

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Nanotechnology has rapidly promoted the development of a new generation of industrial and commercial products; however, it has also raised some concerns about human health and safety. To evaluate the toxicity of the great diversity of nanomaterials (NMs) in the traditional manner, a tremendous number of safety assessments and a very large number of animals would be required. For this reason, it is necessary to consider the use of alternative testing strategies or methods that reduce, refine, or replace (3Rs) the use of animals for assessing the toxicity of NMs. Autophagy is considered an early indicator of NM interactions with cells and has been recently recognized as an important form of cell death in nanoparticle-induced toxicity. Impairment of autophagy is related to the accelerated pathogenesis of diseases. By using mechanism-based high-throughput screening in vitro, we can predict the NMs that may lead to the generation of disease outcomes in vivo. Thus, a tiered testing strategy is suggested that includes a set of standardized assays in relevant human cell lines followed by critical validation studies carried out in animals or whole organism models such as C. elegans (Caenorhabditis elegans), zebrafish (Danio rerio), and Drosophila (Drosophila melanogaster)for improved screening of NM safety. A thorough understanding of the mechanisms by which NMs perturb biological systems, including autophagy induction, is critical for a more comprehensive elucidation of nanotoxicity. A more profound understanding of toxicity mechanisms will also facilitate the development of prevention and intervention policies against adverse outcomes induced by NMs. The development of a tiered testing strategy for NM hazard assessment not only promotes a more widespread adoption of non-rodent or 3R principles but also makes nanotoxicology testing more ethical, relevant, and cost- and time-efficient.

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Section: Autophagy Dysfunction Induced By Nanomaterialsmentioning

confidence: 99%

The Current Understanding of Autophagy in Nanomaterial Toxicity and Its Implementation in Safety Assessment-Related Alternative Testing Strategies

Chen

Liao

et al. 2020

IJMS

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“…The final version may differ from this version. indicating that these NMs triggered pro-death autophagy (Hu et al 2019). This was suggested to be a positive effect of NMs in cancer therapy through the regulation of oxidative stress and autophagy, which led to cell death.…”

Section: Positive Turn-on Effects: Pro-death Nature Of Autophagymentioning

confidence: 88%

An Updated Review on Implications of Autophagy and Apoptosis in Tumorigenesis: Possible Alterations in Autophagy through Engineered Nanomaterials and Their Importance in Cancer Therapy

et al. 2021

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Most commonly recognized as a catabolic pathway, autophagy is a perplexing mechanism through which a living cell can free itself of excess cytoplasmic components, i.e., organelles, by means of certain membranous vesicles or lysosomes filled with degrading enzymes. Upon exposure to external insult or internal stimuli, the cell might opt to activate such pathway through which it can gain control over the maintenance of intracellular components, and thus, sustain homeostasis by intercepting the formation of unnecessary structures or elimination of the already present dysfunctional or inutile organelles. Despite such appropriateness, autophagy, might also be considered a frailty for the cell, as it has been said to have a rather complicated role in tumorigenesis. A merit in the early stages of tumor formation, autophagy appears to be salutary due to its tumor-suppressing effects. In fact, several investigations on tumorigenesis have reported diminished levels of autophagic activity in tumor cells, which might result in transition to malignancy. On the contrary, autophagy has been suggested to be a seemingly favorable mechanism to progressed malignancies, as it contributes to survival of such cells. Based on the recent literature, this mechanism might also be activated upon the entry of engineered nanomaterials inside a cell, supposedly protecting the host from foreign materials. Accordingly, there is a good chance that therapeutic interventions for modulating autophagy in malignant cells using nanoparticles may sensitize cancerous cells to certain treatment modalities, e.g., radiotherapy. In this review, we will discuss the signaling pathways involved in autophagy, and the significance of the mechanism itself in apoptosis and tumorigenesis, while shedding light on possible alterations in autophagy through engineered nanomaterials, and the their potential therapeutic applications in cancer.

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“…The nanocarrier including ZnO enhanced the infiltration of T cells into the tumor tissue compared to mice immunized with PLLA fibers directly conjugated with tumor antigen. Recently, Hu et al [112] showed an enhanced antitumor therapeutic effect in in vivo animal models injected with 4T1 tumor cells, especially in a combinatorial administration with ZnO NPs and doxorubicin (DOX). It was demonstrated that ZnO NPs promoted Atg5-regulated autophagy flux suggesting that autophagy induction by ZnO reinforces cancer cell death by increased Zn ion release and ROS generation when combined with DOX.…”

Section: Zinc Oxide Nanoparticlesmentioning

confidence: 99%

Metal Oxide Nanoparticles as Biomedical Materials

Nikolova

Chavali²

2020

Biomimetics

313

146

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The development of new nanomaterials with high biomedical performance and low toxicity is essential to obtain more efficient therapy and precise diagnostic tools and devices. Recently, scientists often face issues of balancing between positive therapeutic effects of metal oxide nanoparticles and their toxic side effects. In this review, considering metal oxide nanoparticles as important technological and biomedical materials, the authors provide a comprehensive review of researches on metal oxide nanoparticles, their nanoscale physicochemical properties, defining specific applications in the various fields of nanomedicine. Authors discuss the recent development of metal oxide nanoparticles that were employed as biomedical materials in tissue therapy, immunotherapy, diagnosis, dentistry, regenerative medicine, wound healing and biosensing platforms. Besides, their antimicrobial, antifungal, antiviral properties along with biotoxicology were debated in detail. The significant breakthroughs in the field of nanobiomedicine have emerged in areas and numbers predicting tremendous application potential and enormous market value for metal oxide nanoparticles.

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Enhancing tumor chemotherapy and overcoming drug resistance through autophagy-mediated intracellular dissolution of zinc oxide nanoparticles

Abstract: Enhancing tumor chemotherapy and overcoming drug resistance through autophagy-mediated intracellular dissolution of zinc oxide nanoparticles.

Cited by 70 publications

References 67 publications

The Current Understanding of Autophagy in Nanomaterial Toxicity and Its Implementation in Safety Assessment-Related Alternative Testing Strategies

The Current Understanding of Autophagy in Nanomaterial Toxicity and Its Implementation in Safety Assessment-Related Alternative Testing Strategies

An Updated Review on Implications of Autophagy and Apoptosis in Tumorigenesis: Possible Alterations in Autophagy through Engineered Nanomaterials and Their Importance in Cancer Therapy

Metal Oxide Nanoparticles as Biomedical Materials

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