In Vivo T Cell-Targeting Nanoparticle Drug Delivery Systems: Considerations for Rational Design

Abstract

T cells play an important role in immunity and repair and are implicated in diseases, including blood cancers, viral infections, and inflammation, making them attractive targets for the treatment and prevention of diseases. Over recent years, the advent of nanomedicine has shown an increase in studies that use nanoparticles as carriers to deliver therapeutic cargo to T cells for ex vivo and in vivo applications. Nanoparticle-based delivery has several advantages, including the ability to load and protect a variety of drugs, control drug release, improve drug pharmacokinetics and biodistribution, and site-or cell-specific targeting. However, the delivery of nanoparticles to T cells remains a major technological challenge, which is primarily due to the nonphagocytic nature of T cells. In this review, we discuss the physiological barriers to effective T cell targeting and describe the different approaches used to deliver cargo-loaded nanoparticles to T cells for the treatment of disease such as T cell lymphoma and human immunodeficiency virus (HIV). In particular, engineering strategies aiming to improve nanoparticle internalization by T cells, including ligand-based targeting, will be highlighted. These nanoparticle engineering approaches are expected to inspire the development of effective nanomaterials that can target or manipulate the function of T cells for the treatment of T cell-related diseases.

The Cysteine-Containing Cell-Penetrating Peptide AP Enables Efficient Macromolecule Delivery to T Cells and Controls Autoimmune Encephalomyelitis

“…There are numerous potential targets in cells, but delivering macromolecular drugs to cells is technically challenging because of the impermeable cellular membrane [ 24 ]. T cells, especially primary T cells, are more challenging because they are small, non-phagocytic, with a high nuclear–cytoplasmic ratio and low endocytic rate [ 25 , 26 ].…”

Improving the Delivery of Drugs and Nucleic Acids to T Cells Using Nanotechnology

“…Our current knowledge of rational design of nanoparticles for T‐cell targeting suggests that optimal nanoparticles should be between 10 and 100 nm to avoid renal clearance and mononuclear phagocyte system scavenging and should interact with receptors on the T‐cell surface that induce clathrin‐mediated endocytosis for efficient uptake. [ 22 ] Greater discussion in this regard is provided by Cevaal et al [ 22 ]…”

Interfacing Biomaterials with Synthetic T Cell Immunity

“…[ 113 ] Consequently, restricting CAR expression to T cells is among the forefront goals to ensure clinical potency. This could potentially be achieved by using nanocarriers with preferential delivery at both organ [ 114 ] and cell [ 115 ] levels or by implementing cell‐specific promoters to the transgene design.…”