Probing the Ultrastructure of Spheroids and Their Uptake of Magnetic Nanoparticles by FIB–SEM

Mollo, Valentina; Scognamiglio, Paola; Marino, Attilio; Ciofani, Gianni; Santoro, Francesca

doi:10.1002/admt.201900687

Cited by 9 publications

(9 citation statements)

References 30 publications

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“…Since in vitro 3D culture systems mimic the in vivo growth conditions of solid tumors better than conventional monolayer cells cultures [ 28 ], they have been largely adopted as a model for drug and nanomedicine screening [ 29 , 30 ]. Among the numerous spherical cancer models that can be developed, multicellular tumor spheroids (MCTS), which are obtained by growing cancer cell lines under non-adherent conditions, have been reported to accurately mimic the drug sensitivity behavior of in vivo tumors [ 29 , 31 ].…”

Section: Resultsmentioning

confidence: 99%

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Nature-Inspired Nanoparticles as Paclitaxel Targeted Carrier for the Treatment of HER2-Positive Breast Cancer

Nieto

Vega

Valle

2021

Cancers

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Despite the advances made in the fight against HER2-positive breast cancer, the need for less toxic therapies and strategies that avoid the apparition of resistances is indisputable. For this reason, a targeted nanovehicle for paclitaxel and trastuzumab, used in the first-line treatment of this subtype of breast cancer, had already been developed in a previous study. It yielded good results in vitro but, with the aim of further reducing paclitaxel effective dose and its side effects, a novel drug delivery system was prepared in this work. Thus, polydopamine nanoparticles, which are gaining popularity in cancer nanomedicine, were novelty loaded with paclitaxel and trastuzumab. The effectiveness and selectivity of the nanoparticles obtained were validated in vitro with different HER2-overexpressing tumor and stromal cell lines. These nanoparticles showed more remarkable antitumor activity than the nanosystem previously designed and, in addition, to affect stromal cell viability rate less than the parent drug. Moreover, loaded polydopamine nanoparticles, which notably increased the number of apoptotic HER2-positive breast cancer cells after treatment, also maintained an efficient antineoplastic effect when validated in tumor spheroids. Thereby, these bioinspired nanoparticles charged with both trastuzumab and paclitaxel may represent an excellent approach to improve current HER2-positive breast cancer therapies.

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Section: Resultsmentioning

confidence: 99%

“…First, with the aim of analyzing the interaction between the loaded PDA NPs and the 3D cell biostructures, SEM was employed to acquire images of spheroid sections in a secondary electron mode after critical point drying [ 30 ]. These images were taken 48 and 72 h after treatment.…”

Section: Resultsmentioning

confidence: 99%

Nature-Inspired Nanoparticles as Paclitaxel Targeted Carrier for the Treatment of HER2-Positive Breast Cancer

Nieto

Vega

Valle

2021

Cancers

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“…Alternatively, SEM can be combined with a FIB used as a nanoscalpel able to cut thinner sections (<20 nm), avoiding the artefacts associated with the mechanical sectioning. The ultrastructure of spheroids and their uptake of magnetic NCs was investigated by FIB-SEM in Mollo et al [84] (a video of the reconstructed volume is given in the SI section of this publication). In Félix et al, [40] small gold NPs attached to Fe 3 O 4 cores were designed for hyperthermia applications and their distribution was analyzed by FIB-SEM in microglial BV2 cells.…”

Section: Imaging Large Volumes By 3d-semmentioning

confidence: 99%

Deciphering the Structure and Chemical Composition of Drug Nanocarriers: From Bulk Approaches to Individual Nanoparticle Characterization

Chaupard

Frutos

Gref

2021

Part & Part Syst Charact

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payload's pharmacokinetics and contributed to achieve the desired pharmacological response at the target. They are now widely exploited for therapeutic purposes, including the treatment of severe diseases such as cancer and infections. [1] A plethora of natural and synthetic materials have been engineered at a nanoscopic level and explored for drug delivery (Figure 1). Liposomes, the first nanotechnology-based drug delivery system, were discovered early in the 1960s. [2] The first Food and Drug Administration (FDA)-approved nanotechnology was the liposomal Doxil formulation designed for the treatment of Kaposi's sarcoma and since then, more than twenty liposomal and lipid-based formulations have been approved by regular authorities. [3] Many other types of drug nanocarriers have been developed, including polymeric, hybrid or metal nanoparticles (NPs), nanogels, dendrimers, quantum dots, carbon nanotubes (CNTs), and micelles (Figure 1). Several nanotechnologies containing an active molecule or a drug combination, such as Onpattro and Vyxeos, were FDA-approved in recent years, demonstrating the potential of nanomedicine and the growing interest in this field. [4,5] Moreover, the FDA-approved NP-based vaccines represent a giant step in the fight against the COVID-19 pandemic. [6] Nowadays, a large variety of materials is used to prepare drug nanocarriers: i) organic compounds (lipids, synthetic or natural polymers, biomolecules); ii) inorganic materials (silica, carbon networks, metals, or metal oxides) and iii) hybrid organic-inorganic networks combining the properties of both their organic and inorganic counterparts. Generally, drug nanocarriers have a core-shell structure: i) the cores incorporate the drugs and release them in a controlled manner and ii) the shells govern the interactions with the living media (control protein adsorption, avoid recognition by the immune system, allow targeting diseased tissues and organs, confer bio-adhesion properties). Organic compounds remain the most employed materials for drug incorporation and for engineering multifunctional shells. Additionally, the presence of metals in drug nanocarriers' composition offers new functionalities, such as antibacterial or antifungal properties, [7] radioenhancement [8] or imaging abilities for personalized therapies. [9] More recently, nanoscale hybrid metal-organic frameworks (MOFs) emerged as versatile Drug nanocarriers (NCs) with sizes usually below 200 nm are gaining increasing interest in the treatment of severe diseases such as cancer and infections. Characterization methods to investigate the morphology and physicochemical properties of multifunctional NCs are key in their optimization and in the study of their in vitro and in vivo fate. Whereas a variety of methods has been developed to characterize "bulk" NCs in suspension, the scope of this review is to describe the different approaches for the NC characterization on an individual basis, for which fewer techniques are available. The accent is put on methods devoid of labelling, whi...

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“…rapid proliferation at the surface and slow metabolism -or necrosis -in the center of spheroids 25 . The majority of studies of NP distributions in tumor spheroids use tumor spheroid fixation [26][27][28][29][30][31][32][33][34] , often in combination with histological sectioning 7,[35][36][37][38] . Nevertheless, there are also reports of NP penetration in live tumor spheroids using confocal-scanning microscopy [39][40][41][42][43][44][45][46][47][48][49] .…”

Section: Introductionmentioning

confidence: 99%

Head-to-head comparison of the penetration efficiency of lipid-based nanoparticles in a 3D tumor spheroid model

Niora¹,

Pedersbæk²,

Lassen³

et al. 2020

Preprint

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<p>Most tumor-targeted drug delivery systems must overcome a large variety of physiological barriers before reaching the tumor site and diffuse through the tight network of tumor cells. Many studies focus on optimizing the first part, the accumulation of drug carriers at the tumor site, ignoring the penetration efficiency, i.e., a measure of the ability of a drug delivery system to overcome tumor surface adherence and uptake. We used 3D tumor spheroids in combination with light-sheet fluorescence microscopy in a head-to-head comparison of a variety of commonly used lipid-based nanoparticles, including liposomes, PEGylated liposomes, lipoplexes and reconstituted high-density lipoproteins (rHDL). Whilst PEGylation of liposomes only had minor effects on the penetration efficiency, we show that lipoplexes mainly associated to the periphery of tumor spheroids, possibly due to their positive surface charge leading to fusion with the cells at the spheroid surface or aggregation. Surprisingly, the rHDL showed significantly higher penetration efficiency and high accumulation inside the spheroid. While these findings indeed could be relevant when designing novel drug delivery systems based on lipid-based nanoparticles, we stress that the used platform and detailed image analysis is a versatile tool for in vitro studies of the penetration efficiency of nanoparticles in tumors.</p><div><br></div>

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Probing the Ultrastructure of Spheroids and Their Uptake of Magnetic Nanoparticles by FIB–SEM

Cited by 9 publications

References 30 publications

Nature-Inspired Nanoparticles as Paclitaxel Targeted Carrier for the Treatment of HER2-Positive Breast Cancer

Nature-Inspired Nanoparticles as Paclitaxel Targeted Carrier for the Treatment of HER2-Positive Breast Cancer

Deciphering the Structure and Chemical Composition of Drug Nanocarriers: From Bulk Approaches to Individual Nanoparticle Characterization

Head-to-head comparison of the penetration efficiency of lipid-based nanoparticles in a 3D tumor spheroid model

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