Single quantum dot tracking reveals the impact of nanoparticle surface on intracellular state

Abstract

Inefficient delivery of macromolecules and nanoparticles to intracellular targets is a major bottleneck in drug delivery, genetic engineering, and molecular imaging. Here we apply live-cell single-quantum-dot imaging and tracking to analyze and classify nanoparticle states after intracellular delivery. By merging trajectory diffusion parameters with brightness measurements, multidimensional analysis reveals distinct and heterogeneous populations that are indistinguishable using single parameters alone. We derive new quantitative metrics of particle loading, cluster distribution, and vesicular release in single cells, and evaluate intracellular nanoparticles with diverse surfaces following osmotic delivery. Surface properties have a major impact on cell uptake, but little impact on the absolute cytoplasmic numbers. A key outcome is that stable zwitterionic surfaces yield uniform cytosolic behavior, ideal for imaging agents. We anticipate that this combination of quantum dots and single-particle tracking can be widely applied to design and optimize next-generation imaging probes, nanoparticle therapeutics, and biologics.

Compensatory ion transport buffers daily protein rhythms to regulate osmotic balance and cellular physiology

“…The different size and coating of these QDs might account for the different effect size between experiments in Fig.1e and Supplementary Fig. 2b 74 .…”

Inorganic semiconductor biointerfaces

“…However, substrate-bound device internalization is typically achieved by electroporation 86,128 , optoporation 129 or surface modification 31,111 . Freestanding materials or devices can be internalized through spontaneous endocytosis 127,130,131 or microinjection 132 . Intracellular semiconductors are in direct contact with organelles and/or the cytosol, enabling high-fidelity studies of subcellular activities 30,133 .…”

Dye‐Loaded Nanoemulsions: Biomimetic Fluorescent Nanocarriers for Bioimaging and Nanomedicine

“…Up to now, most of particle tracking experiments in cells have been done using quantum dots, because they are 10-100 times brighter than single organic dyes and feature high photostability, which allows robust continuous recording of single-particle traces. [202][203][204] Nowadays, organic NPs started gaining popularity because of improved quantum yield, brightness and controlled small size, which enables them to be tracked with high precision and for longer periods. [205][206][207] Reproduced with permission.…”