Delivery of therapeutic agents and cells to pancreatic islets: Towards a new era in the treatment of diabetes

• Published in: Molecular aspects of medicine Vol. 83; p. 101063
• Main Authors: Zeynaloo, Elnaz, Stone, Logan D., Dikici, Emre, Ricordi, Camillo, Deo, Sapna K., Bachas, Leonidas G., Daunert, Sylvia, Lanzoni, Giacomo
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2022
• Subjects: Beta cells; Cell therapy; Diabetes; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Endothelial Cells - metabolism; Exosomes; Humans; Insulin-Secreting Cells - metabolism; Islets of Langerhans - metabolism; Microvesicles; Nanocarriers; Pancreatic islet; T1D; T2D; Targeted delivery; Type 1 diabetes; Type 2 diabetes; Type 2 diabetes; Cell therapy; MRI; T1D; GPR44; DTBZ; ICAM-1; Exosomes; Pancreatic islet; UC-MSC; ZnT8; VMAT-2; MSC; Nanocarriers; LFA-1; T2D; BM-MSC; Microvesicles; VLA-4; Beta cells; VCAM-1; Targeted delivery; Type 1 diabetes; Diabetes; HCELL; PET; GLP-1R
• ISSN: 0098-2997; 1872-9452; 1872-9452
• DOI: 10.1016/j.mam.2021.101063

Pancreatic islet cells, and in particular insulin-producing beta cells, are centrally involved in the pathogenesis of diabetes mellitus. These cells are of paramount importance for the endocrine control of glycemia and glucose metabolism. In Type 1 Diabetes, islet beta cells are lost due to an autoimmune attack. In Type 2 Diabetes, beta cells become dysfunctional and insufficient to counterbalance insulin resistance in peripheral tissues. Therapeutic agents have been developed to support the function of islet cells, as well as to inhibit deleterious immune responses and inflammation. Most of these agents have undesired effects due to systemic administration and off-target effects. Typically, only a small fraction of therapeutic agent reaches the desired niche in the pancreas. Because islets and their beta cells are scattered throughout the pancreas, access to the niche is limited. Targeted delivery to pancreatic islets could dramatically improve the therapeutic effect, lower the dose requirements, and lower the side effects of agents administered systemically. Targeted delivery is especially relevant for those therapeutics for which the manufacturing is difficult and costly, such as cells, exosomes, and microvesicles. Along with therapeutic agents, imaging reagents intended to quantify the beta cell mass could benefit from targeted delivery. Several methods have been developed to improve the delivery of agents to pancreatic islets. Intra-arterial administration in the pancreatic artery is a promising surgical approach, but it has inherent risks. Targeted delivery strategies have been developed based on ligands for cell surface molecules specific to islet cells or inflamed vascular endothelial cells. Delivery methods range from nanocarriers and vectors to deliver pharmacological agents to viral and non-viral vectors for the delivery of genetic constructs. Several strategies demonstrated enhanced therapeutic effects in diabetes with lower amounts of therapeutic agents and lower off-target side effects. Microvesicles, exosomes, polymer-based vectors, and nanocarriers are gaining popularity for targeted delivery. Notably, liposomes, lipid-assisted nanocarriers, and cationic polymers can be bioengineered to be immune-evasive, and their advantages to transport cargos into target cells make them appealing for pancreatic islet-targeted delivery. Viral vectors have become prominent tools for targeted gene delivery. In this review, we discuss the latest strategies for targeted delivery of therapeutic agents and imaging reagents to pancreatic islet cells.