Formulation of simvastatin within high density lipoprotein enables potent tumour radiosensitisation

Dehghankelishadi, Pouya; Maritz, Michelle F.; Dmochowska, Nicole; Badiee, Parisa; Cheah, Edward; Kempson, Ivan M.; Berbeco, R.; Thierry, Benjamin

doi:10.1016/j.jconrel.2022.04.017

Cited by 10 publications

(4 citation statements)

References 52 publications

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“…Last year, two more publications showed the potential of nanoparticles as radiosensitizers for HNSCC. However, it should be noted that these were not iron oxide nanoparticles and that they were not pure nanoparticles but nanoparticle formulations, so that, in contrast to our study, the radiation-enhancing property cannot be solely attributed to the nanoparticles [ 30 , 31 ].…”

Section: Introductioncontrasting

confidence: 61%

In Vitro Analysis of Superparamagnetic Iron Oxide Nanoparticles Coated with APTES as Possible Radiosensitizers for HNSCC Cells

et al. 2023

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Superparamagnetic iron nanoparticles (SPION) are being investigated for many purposes, e.g., for the amplification of ionizing radiation and for the targeted application of therapeutics. Therefore, we investigated SPIONs coated with (3-Aminopropyle)-Triethoxysilane (SPION-APTES) for their influence on different head and neck squamous cell carcinoma (HNSCC) cell lines, as well as for their suitability as a radiosensitizer. We used 24-well microscopy and immunofluorescence microscopy for cell observation, growth curves to determine cytostatic effects, and colony formation assays to determine cytotoxicity. We found that the APTES-SPIONs were very well taken up by the HNSCC cells. They generally have a low cytotoxic effect, showing no significant difference in clonogenic survival between the control group and cells treated with 20 µg Fe/mL (p > 0.25) for all cell lines. They have a cytostatic effect on some cell lines cells (e.g., Cal33) that is visible across different radiation doses (1, 2, 8 Gy, p = 0.05). In Cal33, e.g., SPION-APTES raised the doubling time at 2 Gy from 24.53 h to 41.64 h. Importantly, these findings vary notably between the cell lines. However, they do not significantly alter the radiation effect: only one out of eight cell lines treated with SPION-APTES showed a significantly reduced clonogenic survival after ionizing radiation with 2 Gy, and only two showed significantly reduced doubling times. Thus, although the APTES-SPIONs do not qualify as a radiosensitizer, we were still able to vividly demonstrate and analyze the effect that the APTES-SPIONs have on various cell lines as a contribution to further functionalization.

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Section: Introductioncontrasting

confidence: 61%

In Vitro Analysis of Superparamagnetic Iron Oxide Nanoparticles Coated with APTES as Possible Radiosensitizers for HNSCC Cells

et al. 2023

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“…Among the myriads of nanoparticle platforms investigated, the mannose-coated polymers-based carriers or liposomal nanoparticles facilitated TAM targeting in several cancer types [ 48 , 64 , 65 , 66 , 67 , 68 , 69 ]. HDL-inspired nanoparticles, including those utilizing ApoA-I mimetic peptides and rHDL NPs, have also been studied and have shown great potential in TAM targeting in the TME [ 70 , 71 , 72 ]. In the present work, we optimized mannose-coated rHDL NPs loaded with DMXAA and evaluated their effectiveness in mediating an M2-to-M1 reversal in vitro.…”

Section: Discussionmentioning

confidence: 99%

Mannose-Coated Reconstituted Lipoprotein Nanoparticles for the Targeting of Tumor-Associated Macrophages: Optimization, Characterization, and In Vitro Evaluation of Effectiveness

et al. 2023

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Reconstituted high-density lipoprotein nanoparticles (rHDL NPs) have been utilized as delivery vehicles to a variety of targets, including cancer cells. However, the modification of rHDL NPs for the targeting of the pro-tumoral tumor-associated macrophages (TAMs) remains largely unexplored. The presence of mannose on nanoparticles can facilitate the targeting of TAMs which highly express the mannose receptor at their surface. Here, we optimized and characterized mannose-coated rHDL NPs loaded with 5,6-dimethylxanthenone-4-acetic acid (DMXAA), an immunomodulatory drug. Lipids, recombinant apolipoprotein A-I, DMXAA, and different amounts of DSPE-PEG-mannose (DPM) were combined to assemble rHDL-DPM-DMXAA NPs. The introduction of DPM in the nanoparticle assembly altered the particle size, zeta potential, elution pattern, and DMXAA entrapment efficiency of the rHDL NPs. Collectively, the changes in physicochemical characteristics of rHDL NPs upon the addition of the mannose moiety DPM indicated that the rHDL-DPM-DMXAA NPs were successfully assembled. The rHDL-DPM-DMXAA NPs induced an immunostimulatory phenotype in macrophages pre-exposed to cancer cell-conditioned media. Furthermore, rHDL-DPM NPs delivered their payload more readily to macrophages than cancer cells. Considering the effects of the rHDL-DPM-DMXAA NPs on macrophages, the rHDL-DPM NPs have the potential to serve as a drug delivery platform for the selective targeting of TAMs.

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“…A parenteral SV-loaded HDL nanoformulation consisting of DPPC and ApoA-1 mimicking peptide was developed and combined with radiotherapy for potent anticancer effects. 89 The researchers found that the effluxed cholesterol content was substantially enhanced (137.8 ± 18.1% vs non-treated cells) after being treated with the HDL nanoformulations for 5 h. The enhanced SV intracellular level and HDL-induced cholesterol efflux may confer radiosensitization of NPs equivalent to 10-fold and 5-fold doses of free SV in 2D and 3D cultures. In vivo experiments also showed that the mean tumor size in the simvastatin-HDL NPs and radiation combination group was the smallest among all treated and control groups, indicating the excellent collaborative therapy effect of HDL nanoformulations.…”

Section: Cholesterol-integrated Tumor Nanotherapeuticsmentioning

confidence: 97%

Regulating Cholesterol in Tumorigenesis: A Novel Paradigm for Tumor Nanotherapeutics

Wu,

Zhao

et al. 2024

IJN

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During the past decade, “membrane lipid therapy”, which involves the regulation of the structure and function of tumor cell plasma membranes, has emerged as a new strategy for cancer treatment. Cholesterol is an important component of the tumor plasma membrane and serves an essential role in tumor initiation and progression. This review elucidates the role of cholesterol in tumorigenesis (including tumor cell proliferation, invasion/metastasis, drug resistance, and immunosuppressive microenvironment) and elaborates on the potential therapeutic targets for tumor treatment by regulating cholesterol. More meaningfully, this review provides an overview of cholesterol-integrated membrane lipid nanotherapeutics for cancer therapy through cholesterol regulation. These strategies include cholesterol biosynthesis interference, cholesterol uptake disruption, cholesterol metabolism regulation, cholesterol depletion, and cholesterol-based combination treatments. In summary, this review demonstrates the tumor nanotherapeutics based on cholesterol regulation, which will provide a reference for the further development of “membrane lipid therapy” for tumors.

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Formulation of simvastatin within high density lipoprotein enables potent tumour radiosensitisation

Cited by 10 publications

References 52 publications

In Vitro Analysis of Superparamagnetic Iron Oxide Nanoparticles Coated with APTES as Possible Radiosensitizers for HNSCC Cells

In Vitro Analysis of Superparamagnetic Iron Oxide Nanoparticles Coated with APTES as Possible Radiosensitizers for HNSCC Cells

Mannose-Coated Reconstituted Lipoprotein Nanoparticles for the Targeting of Tumor-Associated Macrophages: Optimization, Characterization, and In Vitro Evaluation of Effectiveness

Regulating Cholesterol in Tumorigenesis: A Novel Paradigm for Tumor Nanotherapeutics

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