TAT-Modified Gold Nanoparticle Carrier with Enhanced Anticancer Activity and Size Effect on Overcoming Multidrug Resistance

Wang, Ruihui; Bai, Jiang; Deng, Jun; Fang, Chen‐Jie; Chen, Xiaoyuan

doi:10.1021/acsami.6b15200

Cited by 54 publications

(39 citation statements)

References 52 publications

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“… 65 , 66 The cytotoxic effect depends on the size, shape, surface coating, and charge of gold nanoparticles. 67 − 70 Regarding the size of the AuNPs, citrate-stabilized AuNPs of 5 nm have been shown to be cytotoxic at a concentration higher than 50 μM with Balb/3T3 cells. 71 However, Vijayakumar et al found that citrate-capped AuNPs having diameters 5, 6, 10, 17, and 45 nm did not decrease the cell viability of MCF-7 and PC-3 cells.…”

Section: Resultsmentioning

confidence: 99%

“… 69 Furthermore, TAT-modified AuNPs having diameters 3.8 and 22.1 nm showed very low toxicity in HepG 2 cells. 70 AuNPs with 15–150 nm diameters are also biocompatible, and only certain 150 nm PEG-functionalized particles reduced the viability at high concentrations. 72 Huo et al showed that nanoparticles smaller than 10 nm (2 and 6 nm) could preferentially enter the nucleus of the MCF-7 breast cancer cell.…”

Section: Resultsmentioning

confidence: 99%

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Porphyrin–Gold Nanomaterial for Efficient Drug Delivery to Cancerous Cells

et al. 2018

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With an aim to overcome multidrug resistance (MDR), nontargeted delivery, and drug toxicity, we developed a new nanochemotherapeutic system with tetrasodium salt of meso-tetrakis(4-sulfonatophenyl)porphyrin (TPPS) armored on gold nanoparticles (TPPS-AuNPs). The nanocarrier is able to be selectively internalized within tumor cells than in normal cells followed by endocytosis and therefore delivers the antitumor drug doxorubicin (DOX) particularly to the nucleus of diseased cells. The embedment of TPPS on the gold nanosurface provides excellent stability and biocompatibility to the nanoparticles. Porphyrin interacts with the gold nanosurface through the coordination interaction between gold and pyrrolic nitrogen atoms of the porphyrin and forms a strong association complex. DOX-loaded nanocomposite (DOX@TPPS-AuNPs) demonstrated enhanced cellular uptake with significantly reduced drug efflux in MDR brain cancer cells, thereby increasing the retention time of the drug within tumor cells. It exhibited about 9 times greater potency for cellular apoptosis via triggered release commenced by acidic pH. DOX has been successfully loaded on the porphyrin-modified gold nanosurface noncovalently with high encapsulation efficacy (∼90%) and tightly associated under normal physiological conditions but capable of releasing ∼81% of drug in a low-pH environment. Subsequently, DOX-loaded TPPS-AuNPs exhibited higher inhibition of cellular metastasis, invasion, and angiogenesis, suggesting that TPPS-modified AuNPs could improve the therapeutic efficacy of the drug molecule. Unlike free DOX, drug-loaded TPPS-AuNPs did not show toxicity toward normal cells. Therefore, higher drug encapsulation efficacy with selective targeting potential and acidic-pH-mediated intracellular release of DOX at the nucleus make TPPS-AuNPs a “magic bullet” for implication in nanomedicine.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Porphyrin–Gold Nanomaterial for Efficient Drug Delivery to Cancerous Cells

et al. 2018

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“…The IC 50 of DOX for HepG-2 cell line (0.34 mM) matched that recorded in the literature. 52,53 The CI value of OX + DOX in the HepG-2 cell line was 0.62, indicating that in our hands the combination of OX and DOX exhibits a synergistic effect at the cellular level. The CI value of DOX@PtC 10 3CP6A (0.61) was found to match that of OX + DOX, leading us to infer that this self-assembled DDS system promotes a synergistic effect in vitro.…”

Section: In Vitro Cytotoxicity and Cellular Uptakementioning

confidence: 56%

Supramolecular combination chemotherapy: a pH-responsive co-encapsulation drug delivery system

et al. 2020

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“…AuNPs modified with peptides can provide a range of surface functionalities because peptides can provide a valuable resource to control structures and properties of AuNPs [43, 44]. For instance, massive peptide-AuNPs based assays have been developed for detecting different targets including metallic cations, small molecules, nucleic acids, proteins and cells [45].…”

Section: Resultsmentioning

confidence: 99%

The effect of phospho-peptide on the stability of gold nanoparticles and drug delivery

Hou

Wang

et al. 2019

J Nanobiotechnol

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Background Gold nanoparticles (AuNPs) have been proposed for many applications in medicine and bioanalysis. For use in all these applications, maintaining the stability of AuNPs in solution by suppressing aggregation is paramount. Herein, the effects of amino acids were investigated in stabilizing AuNPs by rationally designed peptide scaffolds. Results Compared to other tested amino acids, phosphotyrosine (pY) significantly stabilized AuNPs. Our results indicated that pY modified AuNPs presented a high level of stability in various solutions, and had good biocompatibility. When a pY-peptide was used in stabilizing AuNPs, the phosphate group could be removed by phosphatases, which subsequently caused the aggregation and the cargo release of AuNPs. In vitro study showed that AuNPs formed aggregation in a phosphatase concentration depending manner. The aggregation of AuNPs was well correlated with the enzymatic activity (R 2 = 0.994). In many types of cancer, a significant increase in phosphatases has been observed. Herein, we demonstrated that cancer cells treated with pY modified AuNPs in conjunction with doxorubicin killed SGC-7901 cells with high efficiency, indicating that the pY peptide stabilized AuNPs could be used as carriers for targeted drug delivery. Conclusion In summary, pY peptides can act to stabilize AuNPs in various solutions. In addition, the aggregation of pY-AuNPs could be tuned by phosphatase. These results provide a basis for pY-AuNPs acting as potential drug carriers and anticancer efficacy. Electronic supplementary material The online version of this article (10.1186/s12951-019-0522-y) contains supplementary material, which is available to authorized users.

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TAT-Modified Gold Nanoparticle Carrier with Enhanced Anticancer Activity and Size Effect on Overcoming Multidrug Resistance

Cited by 54 publications

References 52 publications

Porphyrin–Gold Nanomaterial for Efficient Drug Delivery to Cancerous Cells

Porphyrin–Gold Nanomaterial for Efficient Drug Delivery to Cancerous Cells

Supramolecular combination chemotherapy: a pH-responsive co-encapsulation drug delivery system

The effect of phospho-peptide on the stability of gold nanoparticles and drug delivery

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