Toxicology and clinical potential of nanoparticles

Yildirimer, Lara; Thanh, Nguyen Tk; Loizidou, Marilena; Seifalian, Alexander M.

doi:10.1016/j.nantod.2011.10.001

Cited by 557 publications

(297 citation statements)

References 154 publications

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“…Identifying ENMs hazardous to natural organisms is difficult, given the wide variety of NPs, their diverse properties (eg particle material, size, shape, surface, charge, corona) and the complexity of biological entities (eg membrane and media composition, type of cell, cell cycle) [18]. The interaction of inorganic NPs with biological systems can lead to severe cytotoxic effects [17,[19][20][21][22][23][24]. This cytotoxicity of ENMs is reported across a range of studies that highlight the biological impact of the NP exposure [5,[25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Nanoparticle–membrane interactions

Contini

Schneemilch

Gaisford

et al. 2017

Journal of Experimental Nanoscience

143

104

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Engineered nanomaterials have a wide range of applications and as a result, are increasingly present in the environment. While they offer new technological opportunities, there is also the potential for adverse impact, in particular through possible toxicity. In this review, we discuss the current state of the art in the experimental characterisation of nanoparticle-membrane interactions relevant to the prediction of toxicity arising from disruption of biological systems. One key point of discussion is the urgent need for more quantitative studies of nano-bio interactions in experimental models of lipid system that mimic in vivo membranes.

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Section: Introductionmentioning

confidence: 99%

Nanoparticle–membrane interactions

Contini

Schneemilch

Gaisford

et al. 2017

Journal of Experimental Nanoscience

143

104

View full text Add to dashboard Cite

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“…However, high concentrations of nontargeted nanoparticles (in μM) were used in these previous studies, which might be an obstacle when considering the translation to clinical use. Additionally, several types of nanoparticles, including TiO 2 , SiO 2 , iron oxide, etc., have been found to exhibit toxicity when used in relatively high concentrations (23)(24)(25). In our previous work, we designed nuclear membranetargeted gold nanoparticles (AuNPs) for inhibiting cancer cell migration by increasing their nuclear stiffness, which greatly reduced AuNP dosage and could be favorable for clinical applications (26).…”

mentioning

confidence: 99%

Targeting cancer cell integrins using gold nanorods in photothermal therapy inhibits migration through affecting cytoskeletal proteins

Ali

Tang

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

157

111

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Metastasis is responsible for most cancer-related deaths, but the current clinical treatments are not effective. Recently, gold nanoparticles (AuNPs) were discovered to inhibit cancer cell migration and prevent metastasis. Rationally designed AuNPs could greatly benefit their antimigration property, but the molecular mechanisms need to be explored. Cytoskeletons are cell structural proteins that closely relate to migration, and surface receptor integrins play critical roles in controlling the organization of cytoskeletons. Herein, we developed a strategy to inhibit cancer cell migration by targeting integrins, using Arg-Gly-Asp (RGD) peptide-functionalized gold nanorods. To enhance the effect, AuNRs were further activated with 808-nm near-infrared (NIR) light to generate heat for photothermal therapy (PPTT), where the temperature was adjusted not to affect the cell viability/proliferation. Our results demonstrate changes in cell morphology, observed as cytoskeleton protrusions-i.e., lamellipodia and filopodia-were reduced after treatment. The Western blot analysis indicates the downstream effectors of integrin were attracted toward the antimigration direction. Proteomics results indicated broad perturbations in four signaling pathways, Rho GTPases, actin, microtubule, and kinases-related pathways, which are the downstream regulators of integrins. Due to the dominant role of integrins in controlling cytoskeleton, focal adhesion, actomyosin contraction, and actin and microtubule assembly have been disrupted by targeting integrins. PPTT further enhanced the remodeling of cytoskeletal proteins and decreased migration. In summary, the ability of targeting AuNRs to cancer cell integrins and the introduction of PPTT stimulated broad regulation on the cytoskeleton, which provides the evidence for a potential medical application for controlling cancer metastasis.gold nanorods | cytoskeleton | integrin | metastasis | plasmonic photothermal therapy

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“…14,15 Furthermore, adverse outcomes induced by ENMs are dependent on the route of administration, which has been thoroughly reviewed in previous studies. 1 Here, we discuss the recent findings about how the variation of the aforementioned physicochemical properties would determine the safety of ENMs, including both acute response and chronic effects in preclinical experiments, in addition to some major long-term safety assessments that need to be explored further for expediting their translation into clinics.…”

Section: Safety Of Therapeutic and Diagnostic Enmsmentioning

confidence: 99%

“…1,2 With regard to nanomedicine applications, ENMs could be formulated as drug carriers that deliver the therapeutic reagents within the human body and increase their bioavailability and blood circulation half-life. 2 Moreover, these nanocarriers could be functionalized to deliver the drug specifically to the desired target tissues (e.g., tumors) and release the payload sustainably over long periods, thereby eliminating the necessity of multiple drug administration and reducing its cytotoxic side effects toward healthy cells.…”

mentioning

confidence: 99%

Facilitating Translational Nanomedicine via Predictive Safety Assessment

et al. 2017

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Extensive research on engineered nanomaterials (ENMs) has led to the development of numerous nano-based formulations for theranostic purposes. Although some nano-based drug delivery systems already exist on the market, growing numbers of newly designed ENMs exhibit improved physicochemical properties and are being assessed in preclinical stages. While these ENMs are designed to improve the efficacy of current nanobased therapeutic or imaging systems, it is necessary to thoroughly determine their safety profiles for successful clinical applications. As such, our aim in this mini-review is to discuss the current knowledge on predictive safety and structure-activity relationship (SAR) analysis of major ENMs at the developing stage, as well as the necessity of additional long-term toxicological analysis that would help to facilitate their transition into clinical practices. We focus on how the interaction of these nanomaterials with cells would trigger signaling pathways as molecular initiating events that lead to adverse outcomes. These mechanistic understandings would help to design safer ENMs with improved therapeutic efficacy in clinical settings.During the past decades, engineered nanomaterials (ENMs) have been widely used in biomedical applications, such as nanomedicine, bioimaging, and tissue engineering, because of their unique biophysicochemical properties.1,2 With regard to nanomedicine applications, ENMs could be formulated as drug carriers that deliver the therapeutic reagents within the human body and increase their bioavailability and blood circulation half-life.2 Moreover, these nanocarriers could be functionalized to deliver the drug specifically to the desired target tissues (e.g., tumors) and release the payload sustainably over long periods, thereby eliminating the necessity of multiple drug administration and reducing its cytotoxic side effects toward healthy cells.2 In addition to their implementation in drug delivery, ENMs could be used for diagnostic and imaging purposes that would help to monitor the disease and administer the treatment more accurately. 2Past research in nanomedicine has led to the design of various nanomaterial-based therapeutic and diagnostic systems that are being investigated in experimental stages (e.g., in vitro and in vivo) and clinical trials or are commercially available to the corresponding patients (Table 1). Most commercialized nanomaterial-based therapeutic reagents use lipids, proteins, and polymers that could self-assemble and biodegrade with few side effects.3 Because of high biocompatibility of lipids, several commercial liposome-drug formulations have been developed, mostly relying on polyethylene glycol (PEG)-conjugated lipids, such as DOXIL, AmBisome, Epaxal, and Inflexal V, and are under clinical trials focusing on various types of disease treatments. 4,5 Polymer-based nanoparticles (NPs) also present low toxicity, but their surface functionalization may affect their safety. The most commonly used materials include PEG, ploy(lactic-co-glycolic) acid (PLGA...

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Toxicology and clinical potential of nanoparticles

Abstract: Graphical abstractHighlights▶ NP toxicity depends on NP characteristics, administered dose and route. ▶ In vitro toxicity results do not easily translate into in vivo toxicity. ▶ Current research lacks a unifying protocol for the toxicological profiling of NPs.

Cited by 557 publications

References 154 publications

Nanoparticle–membrane interactions

Nanoparticle–membrane interactions

Targeting cancer cell integrins using gold nanorods in photothermal therapy inhibits migration through affecting cytoskeletal proteins

Facilitating Translational Nanomedicine via Predictive Safety Assessment

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