Phenol-Boronic surface functionalization of gold nanoparticles; to induce ROS damage while inhibiting the survival mechanisms of cancer cells

Aguilar, Ludwig Erik; Chalony, Carmen; Kumar, Dinesh; Kim, Cheol Sang

doi:10.1016/j.ijpharm.2021.120267

Cited by 11 publications

(6 citation statements)

References 41 publications

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“…On the other hand, the HSP-70 induction was strongly reduced to 2.3 ng/mL and 3 ng/mL by the heat and NP treatment in SH-SY5Y and MCF-7 ( Figure 8 m,n). These results are in agreement with previous works, where NPs-polyphenols were used in cancer cells [ 93 , 94 ] and triggered the release of the HSP family, followed by the activation of anti-tumoral pathways [ 95 ]. In our work, the synergic effect of Au, polyphenols, and heat enhanced the inactivation of HSP-70, a critical aspect in cancer therapy applications.…”

Section: Resultssupporting

confidence: 93%

Synergistic Effect Induced by Gold Nanoparticles with Polyphenols Shell during Thermal Therapy: Macrophage Inflammatory Response and Cancer Cell Death Assessment

Matteis

Cascione

Rizzello

et al. 2021

Cancers

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Background: In recent decades, gold nanoparticle (Au NP)-based cancer therapy has been heavily debated. The physico-chemical properties of AuNPs can be exploited in photothermal therapy, making them a powerful tool for selectively killing cancer cells. However, the synthetic side products and capping agents often induce a strong activation of the inflammatory pathways of macrophages, thus limiting their further applications in vivo. Methods: Here, we described a green method to obtain stable polyphenol-capped AuNPs (Au NPs@polyphenols), as polyphenols are known for their anti-inflammatory and anticancer properties. These NPs were used in human macrophages to test key inflammation-related markers, such as NF-κB, TNF-α, and interleukins-6 and 8. The results were compared with similar NPs obtained by a traditional chemical route (without the polyphenol coating), proving the potential of Au NPs@polyphenols to strongly promote the shutdown of inflammation. This was useful in developing them for use as heat-synergized tools in the thermal treatment of two types of cancer cells, namely, breast cancer (MCF-7) and neuroblastoma (SH-SY5Y) cells. The cell viability, calcium release, oxidative stress, HSP-70 expression, mitochondrial, and DNA damage, as well as cytoskeleton alteration, were evaluated. Results: Our results clearly demonstrate that the combined strategy markedly exerts anticancer effects against the tested cancer cell, while neither of the single treatments (only heat or only NPs) induced significant changes. Conclusions: Au NP@polyphenols may be powerful agents in cancer treatment.

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Section: Resultssupporting

confidence: 93%

Synergistic Effect Induced by Gold Nanoparticles with Polyphenols Shell during Thermal Therapy: Macrophage Inflammatory Response and Cancer Cell Death Assessment

Matteis

Cascione

Rizzello

et al. 2021

Cancers

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“…The percent cell viability of prepared polymeric micelles was also evaluated against MDA-MB-231 cell lines . IC 50 values of pure CFA and a combination of BTZ+CFA were determined to be 528 ± 3.24 μM and 1172 ± 1.78 μM (Figure S9), respectively.…”

Section: Resultsmentioning

confidence: 99%

“…Freshly prepared BTZ–HP-PCL PMCs, CFA–HP-PCL PMCs, and BTZ+CFA–HP-PCL PMCs were evaluated for drug release at physiological pH (7.4) and acidic pH (5.6) adjusted with 0.1 N HCl to mimic the lysosomal pH at 37 °C. Two milliliters of PMC solution was placed in a dialysis bag (MWCO 5000 Da) and dialyzed in 100 mL of PBS buffer (pH 7.4 or pH 5.6) as release media . After pre-defined time intervals, 2 mL aliquots were withdrawn and replenished with the same amount of respective buffers.…”

Section: Methodsmentioning

confidence: 99%

“…Two milliliters of PMC solution was placed in a dialysis bag (MWCO 5000 Da) and dialyzed in 100 mL of PBS buffer (pH 7.4 or pH 5.6) as release media. 29 After pre-defined time intervals, 2 mL aliquots were withdrawn and replenished with the same amount of respective buffers. Then, each sample was analyzed using RP-HPLC at λ max 270 nm (BTZ) and 280 nm (CFA).…”

Section: %Dlmentioning

confidence: 99%

“…30 The percent cell viability of prepared polymeric micelles was also evaluated against MDA-MB-231 cell lines. 29 IC 50 values of pure CFA and a combination of BTZ+CFA were determined to be 528 ± 3.24 μM and 1172 ± 1.78 μM (Figure S9), respectively. Results concluded that the antitumor effect of BTZ−HP-PCL PMCs on MDA-MB-231 cells was also significant like MCF-7, which is conspicuous by the difference in IC 50 values.…”

Section: In Vitro Studies 351 Cell Cytotoxicity and Viability And Com...mentioning

confidence: 99%

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N-2-Hydroxypropylmethacrylamide–Polycaprolactone Polymeric Micelles in Co-delivery of Proteasome Inhibitor and Polyphenol: Exploration of Synergism or Antagonism

et al. 2022

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Breast cancer leads to the highest mortality among women resulting in a major clinical burden. Multidrug therapy is more efficient in such patients compared to monodrug therapy. Simultaneous combinatorial or co-delivery garnered significant interest in the past years. Caffeic acid (CFA) (a natural polyphenol) has received growing attention because of its anticarcinogenic and antioxidant potential. Bortezomib (BTZ) is a proteasome inhibitor and may be explored for treating breast cancer. Despite its high anticancer activity, the low water solubility and chemical instability restrict its efficacy against solid tumors. In the present study, we designed and investigated a HP-PCL (N-2hydroxypropylmethacrylamide−polycaprolactone) polymeric micellar (PMCs) system for the simultaneous delivery of BTZ and CFA in the treatment of breast cancer. The designed BTZ+CFA−HP-PCL PMCs were fabricated, optimized, and characterized for size, zeta potential, surface morphology, and in vitro drug release. Developed nanosized (174.6 ± 0.24 nm) PMCs showed enhanced cellular internalization and cell cytotoxicity in both MCF-7 and MDA-MB-231 cells. ROS (reactive oxygen species) levels were highest in BTZ−HP-PCL PMCs, while CFA−HP-PCL PMCs significantly (p < 0.001) scavenged the ROS generated in 2′,7′dichlorofluorescein diacetate (DCFH-DA) assay. The mitochondrial membrane potential (MMP) assay revealed intense and significant green fluorescence in both types of cancer cells when treated with BTZ−HP-PCL PMCs (p < 0.001) indicating apoptosis or cell death. The pharmacokinetic studies revealed that BTZ−HP-PCL PMCs and BTZ+CFA−HP-PCL PMCs exhibited the highest bioavailability, enhanced plasma half-life, decreased volume of distribution, and lower clearance rate than the pure combination of drugs. In the organ biodistribution studies, the combination of BTZ+CFA showed higher distribution in the spleen and the heart. Overall findings of in vitro studies surprisingly resulted in better therapeutic efficiency of BTZ−HP-PCL PMCs than BTZ+CFA−HP-PCL PMCs. However, the in vivo tumor growth inhibition study performed in tumor-induced mice concluded that the tumor growth was inhibited by both BTZ−HP-PCL PMCs and BTZ+CFA−HP-PCL PMCs (p < 0.0001) more efficiently than pure BTZ and the combination (BTZ+CFA), which may be due to the conversion of boronate ester into boronic acid. Henceforth, the combination of BTZ and CFA provides further indications to be explored in the future to support the hypothesis that BTZ may work with polyphenol (CFA) in the acidic environment of the tumor.

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Gold nanoparticle-based drug nanocarriers as a targeted drug delivery system platform for cancer therapeutics: a systematic review

Rosyidah,

Kerdtoob,

Yudhistyra

et al. 2023

Gold Bull

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Phenol-Boronic surface functionalization of gold nanoparticles; to induce ROS damage while inhibiting the survival mechanisms of cancer cells

Cited by 11 publications

References 41 publications

Synergistic Effect Induced by Gold Nanoparticles with Polyphenols Shell during Thermal Therapy: Macrophage Inflammatory Response and Cancer Cell Death Assessment

Synergistic Effect Induced by Gold Nanoparticles with Polyphenols Shell during Thermal Therapy: Macrophage Inflammatory Response and Cancer Cell Death Assessment

N-2-Hydroxypropylmethacrylamide–Polycaprolactone Polymeric Micelles in Co-delivery of Proteasome Inhibitor and Polyphenol: Exploration of Synergism or Antagonism

Gold nanoparticle-based drug nanocarriers as a targeted drug delivery system platform for cancer therapeutics: a systematic review

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