Protein nanoparticles in molecular, cellular, and tissue imaging

Abstract

The quest to develop ideal nanoparticles capable of molecular, cellular, and tissue level imaging is ongoing. Since certain imaging probes and nanoparticles face drawbacks such as low aqueous solubility, increased ROS generation leading to DNA damage, apoptosis, and high cellular/organ toxicities, the development of versatile and biocompatible nanocarriers becomes necessary. Protein nanoparticles (PNPs) are one such promising class of nanocarriers that possess most of the desirable properties of an ideal nanocarrier for bioimaging applications. PNPs demonstrate high aqueous solubility, minimal cytotoxicity, and multi‐cargo loading capacity. They are also amenable to surface‐functionalization, as well as modulation of their hydrophobicity and hydrophilicity. The use of PNPs for bioimaging applications has made rapid advancements in the past two decades. Being comparatively less explored, the field opens up a plethora of opportunities and focus areas to engineer ideal bioimaging protein nanocarriers. The use of PNPs as carriers of their natural ligands as well as other heavy metals and fluorescent probes, along with drug molecules for combined theranostic applications has been reported. In addition, surface functionalization to impart specificity of targeting the PNPs has been shown to reduce nonspecific cellular interactions, thus reducing systemic toxicity. PNPs have been explored for their application in imaging of numerous cancers, cardiovascular diseases as well as imaging of the brain using near infrared fluorescence (NIRF) imaging, magnetic resonance imaging (MRI), X‐ray computed tomography (CT), positron emission tomography (PET), single‐photon emission computed tomography (SPECT), ultrasound (US), and photoacoustic (PA) imaging. This article is categorized under: Biology‐Inspired Nanomaterials > Protein and Virus‐Based Structures Diagnostic Tools > In Vivo Nanodiagnostics and Imaging

Engineering Self-Assembling Protein Nanoparticles for Therapeutic Delivery

“…Combining minimally invasive diagnostic techniques with therapeutic delivery, “theranostics” conveniently synergizes the strengths of two medical procedures. ,,− Noninvasive imaging techniques like magnetic resonance imaging (MRI) are vital for diagnosing and treating disease, yet have low resolution at the cellular and molecular level. Protein nanoparticles can provide alternative optical properties and could be engineered to inform researchers or physicians about real-time cellular and molecular processes through environmental responsiveness. , However, knowledge on protein nanoparticle pharmacokinetics and biodistribution is often lacking . The ability to switch between “imaging mode” (e.g., encapsulating gadolinium) and “therapeutic mode” (e.g., encapsulating a small molecule drug), or to simultaneously operate in both modes, offers an opportunity to more deeply probe the in vivo behavior of protein nanoparticles.…”

“…174,175 However, knowledge on protein nanoparticle pharmacokinetics and biodistribution is often lacking. 176 The ability to switch between "imaging mode" (e.g., encapsulating gadolinium) and "ther-apeutic mode" (e.g., encapsulating a small molecule drug), or to simultaneously operate in both modes, offers an opportunity to more deeply probe the in vivo behavior of protein nanoparticles. Ferritin was recently used in this manner to deliver a cytotoxic peptide to tumors while simultaneously displaying green fluorescent protein (GFP) (Figure 8A−C).…”

Advances in magnetic resonance imaging contrast agents for glioblastoma-targeting theranostics

“…Surface NP modification improves colloidal stability, blood retention time and biocompatibility, and protects NPs from clearance by the MPS. The physical characteristics of NPs, including hydrophobicity, hydrophilicity, surface charge, size and shape, are important parameters to consider when modifying NPs for targeting GBMs [ 87–89 ].…”

Understanding Virus Structure and Dynamics through Molecular Simulations

“…Interfering with any of these stages provides a potential mechanism for antiviral therapeutic applications . For example, the timing of capsid assembly or aberrant assembly can be modulated/produced by small molecules. − In addition to drug-discovery efforts, the self-assembly of capsid proteins into shells has led to applications in medicinal engineering, such as for drug delivery and imaging. − Continued development of novel antivirals and engineering applications relies on a detailed knowledge of the structure and function of these viral systems.…”