Copper Sulfide Facilitates Hepatobiliary Clearance of Gold Nanoparticles through the Copper-Transporting ATPase ATP7B

The surface modification of nanoparticles (NPs) can enhance cellular and intracellular targeting. A new type of polyamine-modified gold NPs (AuNPs) are designed and synthesized, which can be selectively absorbed onto the cell membrane. AuNPs with an average diameter of 4.0 nm were prepared and modified with polyamine (R-4C) through amidation. In order to detect the distribution of NPs within cells by fluorescence imaging, AuNP@MPA-R-4C was functionalized with fluorescein isothiocyanate (FITC). The fluorescence-labled NPs AuNP@MPA-R-4C-FITC demonstrated minimal cytotoxicity in several cell lines. Both confocal laser scanning microscopy and transmission electron microscopy demonstrated that AuNP@MPA-R-4C-FITC was distributed on the cell membrane. Compared with the free organic dye, the modified AuNPs showed significantly increased accumulation on the cell membrane after treatment for only 10 min. These results suggested that AuNP@MPA-R-4C-FITC can be used as a bioprobe targeting the cell membrane for various biological applications.

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“…Some NPs disintegrated in the endolysosomal compartments of HepG2 cells, followed by slow metabolism. 34,35…”

Section: Resultsmentioning

confidence: 99%

Polyamine-Modified Gold Nanoparticles Readily Adsorb on Cell Membranes for Bioimaging

Zhu

Cai

et al. 2019

ACS Omega

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“…In addition, it has been demonstrated that the extraction of PEGylated HCuSNPs was strongly correlated to the P‐type ATPase Cu transporter ATP7B, which could mediate the exocytosis of nanosized CuS nanoagents to induce the quick hepatobiliary excretion (Figure 29b). [ 245 ] The as‐established ATP7B‐mediated hepatobiliary CuS excretion was further used to augment the metabolism of Au nanoparticles out of the body based on the construction of CuS–Au nanoconjugates, which was signified by the combination of 80 nm sized HCuSNPs with 40 nm sized Au nanoparticles and integration of 5 nm sized CuS nanoparticles with Au nanorods (length: 40 nm; width: 10 nm).…”

Section: Biological Effect and Biosafety Of Cu‐involved Nanosystemsmentioning

confidence: 99%

“…CuS-Au Biological effect Augmenting the metabolism of Au nanoparticles out of the body by ATP7B-mediated hepatobiliary CuS excretion. [245] for strengthening the theranostic performances in the following researches. In addition, as compared to traditional Fe/Mn-based nanomedicines, Cu-involved nanosystems are still in the infancy for biomedical use, indicating that they have more properties and applications to be exploited in the future developments, besides the aforementioned several representative biomedical aspects.…”

mentioning

confidence: 99%

The Coppery Age: Copper (Cu)‐Involved Nanotheranostics

et al. 2020

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As an essential trace element in the human body, transitional metal copper (Cu) ions are the bioactive components within the body featuring dedicated biological effects such as promoting angiogenesis and influencing lipid/glucose metabolism. The recent substantial advances of nanotechnology and nanomedicine promote the emerging of distinctive Cu‐involved biomaterial nanoplatforms with intriguing theranostic performances in biomedicine, which are originated from the biological effects of Cu species and the physiochemical attributes of Cu‐composed nanoparticles. Based on the very‐recent significant progresses of Cu‐involved nanotheranostics, this work highlights and discusses the principles, progresses, and prospects on the elaborate design and rational construction of Cu‐composed functional nanoplatforms for a diverse array of biomedical applications, including photonic nanomedicine, catalytic nanotherapeutics, antibacteria, accelerated tissue regeneration, and bioimaging. The engineering of Cu‐based nanocomposites for synergistic nanotherapeutics is also exemplified, followed by revealing their intrinsic biological effects and biosafety for revolutionizing their clinical translation. Finally, the underlying critical concerns, unresolved hurdles, and future prospects on their clinical uses are analyzed and an outlook is provided. By entering the “Copper Age,” these Cu‐involved nanotherapeutic modalities are expected to find more broad biomedical applications in preclinical and clinical phases, despite the current research and developments still being in infancy.

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“…Previous literature indicates that AuNPs are rapidly eliminated from the body via renal clearance [ 42 , 43 ]. Other studies have also shown that the size, composition, shape, and surface charge of AuNP nanoparticles may also direct clearance via the hepatobiliary pathway[ 44 , 45 ]. Evaluation of treatment toxicity was assessed using H&E histological staining ( Fig 3 ).…”

Section: Resultsmentioning

confidence: 99%

“…clearance via the hepatobiliary pathway [44,45]. Evaluation of treatment toxicity was assessed using H&E histological staining (Fig 3).…”

Section: Plos Onementioning

confidence: 99%

Noninvasive imaging of tumor hypoxia after nanoparticle-mediated tumor vascular disruption

et al. 2020

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We have previously demonstrated that endothelial targeting of gold nanoparticles followed by external beam irradiation can cause specific tumor vascular disruption in mouse models of cancer. The induced vascular damage may lead to changes in tumor physiology, including tumor hypoxia, thereby compromising future therapeutic interventions. In this study, we investigate the dynamic changes in tumor hypoxia mediated by targeted gold nanoparticles and clinical radiation therapy (RT). By using noninvasive whole-body fluorescence imaging, tumor hypoxia was measured at baseline, on day 2 and day 13, post-tumor vascular disruption. A 2.5-fold increase (P<0.05) in tumor hypoxia was measured two days after combined therapy, resolving by day 13. In addition, the combination of vascular-targeted gold nanoparticles and radiation therapy resulted in a significant (P<0.05) suppression of tumor growth. This is the first study to demonstrate the tumor hypoxic physiological response and recovery after delivery of vascular-targeted gold nanoparticles followed by clinical radiation therapy in a human non-small cell lung cancer athymic Foxn1 nu mouse model.

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Copper Sulfide Facilitates Hepatobiliary Clearance of Gold Nanoparticles through the Copper-Transporting ATPase ATP7B

Cited by 28 publications

References 27 publications

Polyamine-Modified Gold Nanoparticles Readily Adsorb on Cell Membranes for Bioimaging

Polyamine-Modified Gold Nanoparticles Readily Adsorb on Cell Membranes for Bioimaging

The Coppery Age: Copper (Cu)‐Involved Nanotheranostics

Noninvasive imaging of tumor hypoxia after nanoparticle-mediated tumor vascular disruption

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