Combining cryo-TEM and energy-filtered TEM for imaging organic core-shell nanoparticles and defining the polymer distribution

Weiss, Agnes-Valencia; Koch, Marcus; Schneider, Marc

doi:10.1016/j.ijpharm.2019.118650

Cited by 7 publications

(6 citation statements)

References 29 publications

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“…For example, the distributions of three drugs (heparin, protamine and ferumoxytol) were detected in NCs based on their respective signals of sulfur, nitrogen, and iron (Figure 5E). [68] In Weiss et al, [69] gelatin coating was (hardly) detected on the surface of poly (lactic-coglycolic acid) (PLGA) NPs by its weak nitrogen signal. However, energy filter TEM (EFTEM) is delicate and limited to some elements with intense edges clearly visible.…”

Section: Analytical Em Approaches (Edx Eels and Eftem)mentioning

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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Section: Analytical Em Approaches (Edx Eels and Eftem)mentioning

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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Section: Morphological Characterization (Sem and Tem)mentioning

confidence: 99%

“…These properties indicate that this material's volume was appropriate for its use in several applications that would require the capsules to take up as little space as possible (e.g., incorporation into coatings or layers). It can be seen from the transmission electron microscopy images (Figure 3) that there was a thin shell on the outside of the polymeric core [38,39]. The thin shell of P(MAA-co-EGDMA) around the core of PMMA protects and surrounds the core, while on the other hand it can easily be weakened and removed without the use of a great amount of energy, if an application requires the core to be exposed relatively easy for the selective release of ingredients encapsulated in the core (e.g., targeted delivery or coatings).…”

Section: Morphological Characterization (Sem and Tem)mentioning

confidence: 99%

Synthesis and Characterization of a Core-Shell Copolymer with Different Glass Transition Temperatures

Goulis

Kartsonakis

Charitidis

2020

Fibers

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The aim of this study is to synthesize an organic core-shell co-polymer with a different glass transition temperature (Tg) between the core and the shell that can be used for several applications such as the selective debonding of coatings or the release of encapsulated materials. The co-polymer was synthesized using free radical polymerization and was characterized with respect to its morphology, composition and thermal behavior. The obtained results confirmed the successful synthesis of the co-polymer copolymer poly(methyl methacrylate)@poly(methacrylic acid-co-ethylene glycol dimethacrylate), PMMA@P(MAA-co-EGDMA), which can be used along with water-based solvents. Furthermore, the Tg of the polymer’s core PMMA was 104 °C, while the Tg of the shell P(MAA-co-EGDMA) was 228 °C, making it appropriate for a wide variety of applications. It is worth mentioning that by following this specific experimental procedure, methacrylic acid was copolymerized in water, as the shell of the copolymer, without forming a gel-like structure (hydrogel), as happens when a monomer is polymerized in aqueous media, such as in the case of super-absorbent polymers. Moreover, the addition and subsequent polymerization of the monomer methyl methacrylate (MAA) into the mixture of the already polymerized PMMA resulted in a material that was uniform in size, without any agglomerations or sediments.

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“…Scanning transmission electron microscopy ((S)TEM) equipped with an electron energy loss spectrometer can address the challenge of a full characterisation of PLA-PEG NPs because it can determine morphology, structure and chemistry at the single particle level (for a brief electron microscopy background, see Supporting Information 1). Complete native state analysis of NPs is possible by capturing aqueous suspensions in rapidly frozen, vitreous ice followed by transfer into a microscope for cryogenic (S)TEM imaging with electron energy loss spectroscopy (cryo-STEM-EELS) [ [31] , [32] , [33] , [34] , [35] ]. Cryo-phase contrast TEM imaging can be used to analyse the particle size distribution, shape and internal packing [ 34 ].…”

Section: Introductionmentioning

confidence: 99%

“…Complete native state analysis of NPs is possible by capturing aqueous suspensions in rapidly frozen, vitreous ice followed by transfer into a microscope for cryogenic (S)TEM imaging with electron energy loss spectroscopy (cryo-STEM-EELS) [ [31] , [32] , [33] , [34] , [35] ]. Cryo-phase contrast TEM imaging can be used to analyse the particle size distribution, shape and internal packing [ 34 ]. Cryo annular dark field STEM (cryo-ADF-STEM) imaging can complement the phase contrast imaging by identifying changes in material density within particles and potentially composition too [ 36 ].…”

Section: Introductionmentioning

confidence: 99%

Structure of polymeric nanoparticles encapsulating a drug – pamoic acid ion pair by scanning transmission electron microscopy

Koniuch

Ilett

Collins

et al. 2023

Heliyon

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Combining cryo-TEM and energy-filtered TEM for imaging organic core-shell nanoparticles and defining the polymer distribution

Cited by 7 publications

References 29 publications

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

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

Synthesis and Characterization of a Core-Shell Copolymer with Different Glass Transition Temperatures

Structure of polymeric nanoparticles encapsulating a drug – pamoic acid ion pair by scanning transmission electron microscopy

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