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

Abstract

T cells play several roles in antitumor immunity, including mediating cytotoxicity, generating immune memory, and promoting humoral immunity. Given these critical roles, T cells are the therapeutic target of immunotherapies that have achieved clinical success, notably immune checkpoint inhibitors and chimeric antigen receptor T‐cell therapy. However, a fraction of patients benefits from these treatments due to intolerable toxicities and limited efficacy. These issues stem in part from inefficient and nonselective drug delivery to T cells. Nanotechnology may help resolve these delivery issues, as nanoparticles can serve as modular drug delivery vehicles with targeting abilities that can be applied for ex vivo and in vivo delivery. Herein, applications of nanotechnology in improving extracellular delivery of cytokines and small molecule drugs and intracellular delivery of siRNA to T cells are described. An overview of nanoparticle‐mediated delivery of nucleic acids for chimeric antigen receptor T‐cell therapy and CRISPR/Cas9 genome editing is provided. Finally, an outlook on the challenges and opportunities for the advancement of nanoparticle‐mediated drug delivery to T cells is shared.

Inhibition of c-Rel expression in myeloid and lymphoid cells with distearoyl -phosphatidylserine (DSPS) liposomal nanoparticles encapsulating therapeutic siRNA

“…While this method has multiple advantages, however, as electroporation permeabilizes cell membranes, it can compromise cell viability and affect cell function [ 105 – 108 ]. Moreover, electroporation must be conducted ex vivo and cannot transfect endogenous lymphocytes, which limits its therapeutic applications [ 98 , 109 – 113 ].…”

Nucleic acid drug and delivery techniques for disease therapy: Present situation and future prospect

“…50,51 The indications for small nucleic acid drugs cover a wide range. 52 Among them, cancers and rare diseases are the most widely applied fields of small nucleic acid drugs. 53,54 To date, more than 50 small nucleic acid drugs in the world are in the clinical research stage, covering nerve, cardiovascular, infection and tumor fields.…”

“…The indications for small nucleic acid drugs cover a wide range 52 . Among them, cancers and rare diseases are the most widely applied fields of small nucleic acid drugs 53,54 .…”

The Development of Chiral Nanoparticles to Target NK Cells and CD8+ T Cells for Cancer Immunotherapy

“…[26,28] We know that nanoparticle (NP)-based vaccines (nanovaccines) have generated significant hope with regard to the induction of immune responses against cancer. [29][30][31][32][33][34][35][36][37][38][39] Nanomaterials with chiral optical activity can influence cell uptake, [40] neural stem cell differentiation, [41] the metabolism of nanomaterials in vivo, [42] and possess enormous potential as biosensors, [43][44][45] antitumor agents, [46,47] and therapeutic agents against neurodegenerative disease. [48,49] However, the antitumor effects of chiral nanomaterials on the induction of immune responses have yet to be investigated.…”