Nanoscale chemical imaging of individual chemotherapeutic cytarabine-loaded liposomal nanocarriers

Abstract

Dosage of chemotherapeutic drugs is a tradeoff between efficacy and side-effects. Liposomes are nanocarriers that increase therapy efficacy and minimize side-effects by delivering otherwise difficult to administer therapeutics with improved efficiency and selectivity. Still, variabilities in liposome preparation require assessing drug encapsulation efficiency at the single liposome level, an information that, for non-fluorescent therapeutic cargos, is inaccessible due to the minute drug load per liposome. Photothermal induced resonance (PTIR) provides nanoscale compositional specificity, up to now, by leveraging an atomic force microscope (AFM) tip contacting the sample to transduce the sample’s photothermal expansion. However, on soft samples (e.g. liposomes) PTIR effectiveness is reduced due to the likelihood of tip-induced sample damage and inefficient AFM transduction. Here, individual liposomes loaded with the chemotherapeutic drug cytarabine are deposited intact from suspension via nES-GEMMA (nano-electrospray gas-phase electrophoretic mobility molecular analysis) collection and characterized at the nanoscale with the chemically-sensitive PTIR method. A new tapping-mode PTIR imaging paradigm based on heterodyne detection is shown to be better adapted to measure soft samples, yielding cytarabine distribution in individual liposomes and enabling classification of empty and drug-loaded liposomes. The measurements highlight PTIR capability to detect ≈ 103 cytarabine molecules (≈ 1.7 zmol) label-free and non-destructively.

Chemical Identification of Interlayer Contaminants within van der Waals Heterostructures

“…Because the cantilever oscillation amplitude is proportional to the local absorption coefficient in the sample, 28 in a first approximation, PTIR enables identification of materials 27 and chemical groups 32 by comparison with far-field IR spectral databases. Also, since the PTIR signal derives from the rapid sample expansion rather than the slower heat diffusion, 33 spatial resolutions as high as ≈ 20 nm 34,35 in contact mode or ≈ 10 nm in tapping-mode 36 are possible. Other recent PTIR innovations include the extension to the visible spectral range 35 and operation in a water environment.…”

Virus-like particle size and molecular weight/mass determination applying gas-phase electrophoresis (native nES GEMMA)

“…Besides yielding information on analyte surface-dry particle size and size distribution, particle number concentration detection is possible in accordance with recommendations of the European Commission for characterization of nanoparticle material (2011/696/EU from October 18 th , 2011). Furthermore, analytes can be size-selected for further analyses employing orthogonal methods for instance electron microscopy [43], atomic force microscopy [44], spectroscopic techniques [45, 46], or antibody-based nanoparticle recognition [44, 47]. It is of note that LiquiScan ES, MacroIMS, and SMPS are synonyms of the same instrument found in literature.…”

Yellow-Emitting Hydrophobic Carbon Dots via Solid-Phase Synthesis and Their Applications

“…Liposome is a carrier with excellent biological compatibility and is often used to wrap fat-soluble drug molecules or fluorescent nanoparticles for drug delivery 45 and in vivo imaging. 46 As shown in Figure 8 , since HCDs can insert into the lipid bilayer of liposomes to form liposome–CD (Lipo-CDs) nanostructures, they possess the merits of both: the excellent optical properties of HCDs and the biocompatibility of liposomes. The supporting software of fluorescence microscope MvImage vt 1.0 n was used to measure the average particle size of lipo-CD nanostructures, and the average diameter is 400 nm.…”