Nanotechnology: Deliver on a promise

Wright, Jessica

doi:10.1038/509s58a

Cited by 34 publications

(22 citation statements)

References 3 publications

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“…Cancer nanomedicine, which refers to nanocarriers loaded with anticancer drugs, has been extensively explored as a new advanced technology for cancer chemotherapy . Therapeutic advantages of nanomedicines include enhanced drug bioavailability and therapeutic superiority via enhanced permeation and retention (EPR) effects .…”

Section: Introductionmentioning

confidence: 99%

Paraptosis‐Inducing Nanomedicine Overcomes Cancer Drug Resistance for a Potent Cancer Therapy

Zhou

Huang

Yang

et al. 2018

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Most chemotherapeutic drugs and their nanomedicine formulations exert anticancer activity by inducing cancer cell apoptosis. However, cancer cells inherently have and acquire many antiapoptosis mechanisms, causing cancer drug resistance and poor prognoses in patients. Herein, a potent paraptosis‐inducing nanomedicine is reported that causes quick nonapoptotic death of cancer cells, overcoming apoptosis‐based resistance and effectively inhibiting drug‐resistant tumor growth. The nanomedicine is composed of micelles made from an amphiphilic 8‐hydroxyquinoline (HQ)‐conjugate block copolymer with polyethylene glycol. Cu2+ can catalyze the hydrolysis of the HQ conjugation linker and liberate HQ, and these molecules can form the complex Cu(HQ)2, a strong proteasome inhibitor effective at inducing cell paraptosis. In vivo, the Cu2+‐responsive HQ‐releasing micelles respond to elevated tumor Cu2+ levels or externally administered Cu2+ and effectively inhibit the growth of human breast adenocarcinoma doxorubicin‐resistant (MCF‐7/ADR) tumors. Compared with other nanomedicines that overcome drug resistance via delivering several agents or even siRNA, this paraptosis‐inducing nanomedicine provides a simple but potent approach to overcoming cancer drug resistance.

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Section: Introductionmentioning

confidence: 99%

Paraptosis‐Inducing Nanomedicine Overcomes Cancer Drug Resistance for a Potent Cancer Therapy

Zhou

Huang

Yang

et al. 2018

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“…Due to the positively-charged surface, cationic nanocarriers could load and condense nucleic acids simply by electrical interaction with anionic nucleic cargo. Cationic nanocarriers also have other advantages such as simplicity in large-scale production and less stringent vector size limitations while compared with viral vectors 9 , 10 . Although the benefits brought by nanocarriers in drug delivery have gained much attention and considerable efforts have been devoted to seeking and investigating better cationic carriers, toxicities have always been main barriers in the cationic carrier application 11 .…”

Section: Introductionmentioning

confidence: 99%

Cationic nanocarriers induce cell necrosis through impairment of Na+/K+-ATPase and cause subsequent inflammatory response

et al. 2015

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Nanocarriers with positive surface charges are known for their toxicity which has limited their clinical applications. The mechanism underlying their toxicity, such as the induction of inflammatory response, remains largely unknown. In the present study we found that injection of cationic nanocarriers, including cationic liposomes, PEI, and chitosan, led to the rapid appearance of necrotic cells. Cell necrosis induced by cationic nanocarriers is dependent on their positive surface charges, but does not require RIP1 and Mlkl. Instead, intracellular Na+ overload was found to accompany the cell death. Depletion of Na+ in culture medium or pretreatment of cells with the Na+/K+-ATPase cation-binding site inhibitor ouabain, protected cells from cell necrosis. Moreover, treatment with cationic nanocarriers inhibited Na+/K+-ATPase activity both in vitro and in vivo. The computational simulation showed that cationic carriers could interact with cation-binding site of Na+/K+-ATPase. Mice pretreated with a small dose of ouabain showed improved survival after injection of a lethal dose of cationic nanocarriers. Further analyses suggest that cell necrosis induced by cationic nanocarriers and the resulting leakage of mitochondrial DNA could trigger severe inflammation in vivo, which is mediated by a pathway involving TLR9 and MyD88 signaling. Taken together, our results reveal a novel mechanism whereby cationic nanocarriers induce acute cell necrosis through the interaction with Na+/K+-ATPase, with the subsequent exposure of mitochondrial damage-associated molecular patterns as a key event that mediates the inflammatory responses. Our study has important implications for evaluating the biocompatibility of nanocarriers and designing better and safer ones for drug delivery.

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“…Nanotechnology is in the spotlight of therapeutic innovation 3 , and AuNPs are particularly promising tools to improve cancer treatment 4 . Due to their unique optical properties, non-toxic nature, relatively simple preparation and functionalization, AuNPs are excellent candidates for many biological applications, such as imaging, drug delivery and photothermal therapy.…”

Section: Introductionmentioning

confidence: 99%

Off to the Organelles - Killing Cancer Cells with Targeted Gold Nanoparticles

Kodiha¹,

Wang²,

Hutter³

et al. 2015

Theranostics

149

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Gold nanoparticles (AuNPs) are excellent tools for cancer cell imaging and basic research. However, they have yet to reach their full potential in the clinic. At present, we are only beginning to understand the molecular mechanisms that underlie the biological effects of AuNPs, including the structural and functional changes of cancer cells. This knowledge is critical for two aspects of nanomedicine. First, it will define the AuNP-induced events at the subcellular and molecular level, thereby possibly identifying new targets for cancer treatment. Second, it could provide new strategies to improve AuNP-dependent cancer diagnosis and treatment.Our review summarizes the impact of AuNPs on selected subcellular organelles that are relevant to cancer therapy. We focus on the nucleus, its subcompartments, and mitochondria, because they are intimately linked to cancer cell survival, growth, proliferation and death. While non-targeted AuNPs can damage tumor cells, concentrating AuNPs in particular subcellular locations will likely improve tumor cell killing. Thus, it will increase cancer cell damage by photothermal ablation, mechanical injury or localized drug delivery. This concept is promising, but AuNPs have to overcome multiple hurdles to perform these tasks. AuNP size, morphology and surface modification are critical parameters for their delivery to organelles. Recent strategies explored all of these variables, and surface functionalization has become crucial to concentrate AuNPs in subcellular compartments.Here, we highlight the use of AuNPs to damage cancer cells and their organelles. We discuss current limitations of AuNP-based cancer research and conclude with future directions for AuNP-dependent cancer treatment.

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Nanotechnology: Deliver on a promise

Cited by 34 publications

References 3 publications

Paraptosis‐Inducing Nanomedicine Overcomes Cancer Drug Resistance for a Potent Cancer Therapy

Paraptosis‐Inducing Nanomedicine Overcomes Cancer Drug Resistance for a Potent Cancer Therapy

Cationic nanocarriers induce cell necrosis through impairment of Na+/K+-ATPase and cause subsequent inflammatory response

Off to the Organelles - Killing Cancer Cells with Targeted Gold Nanoparticles

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