Table 1.

Cargos, Vehicles, and Targeting moieties for islet-targeted therapeutic agents.

Purpose	Cargo	Vehicle	Targeting Moiety/Target/Strategy	Outcome	Reference
Targeted delivery of an immunosuppressant drug to islet cells	Genistein	PLGA/PEG-COOH	Islet Targeting Peptide (Cyclic) (CHVLWSTRKC)/EphA4 Receptor	200x increased immunosuppressant effect	Ghosh et al. (2012)
Islet beta cells proliferation/Decreased expression of phosphatase and tensin homolog (PTEN)	miR-216 mimics/inhibitors	Iron Oxide Nanoparticles	miR-216 mimics/inhibitors	Decreased PTEN expression and increased beta cell proliferation	Wang et al. (2020)
Prevention of autoimmunity to islet components	Autoimmune diabetes relevant peptide/CRISPR-Cas9 plasmid	PLGA/PEG-COOH	Three separate guide RNAs for CD80, CD86 and CD40/CD80, CD86 and CD40	Prevention of autoimmunity to islet components and inhibition of T1D development	Luo et al. (2020)
Delivery of antisense oligonucleotides (ASO) to beta cells for knocking down islet amyloid polypeptide	Antisense oligonucleotides (ASO)	Glucagon Like Peptide 1 Receptor (GLP1R) agonist peptide ligands	GLP1R agonist peptide ligands/GLP1 Receptor	Successful knocking down of islet amyloid polypeptide	Knerr et al. (2021)
Polymeric gene delivery system to deliver a plasmid coding for soluble RAE-1γ to the pancreatic islet microvasculature	Soluble Retinoic acid early inducible gene-1 (RAE-1) Plasmid	Poly(cystamine bisacrylamide–diamino hexane) (p(CBA-DAH))/poly(ethylene glycol) (PEG)	CHVLWSTRC Peptide/EphA2 and EphA4 receptors	Protection of beta cells from autoimmune destruction and prevention of type 1 diabetes.	Blevins et al. (2012) Joo et al. (2012)
19F MRI imaging of the transplanted human islets	Rhodamine	Perfluorooctylbromide (PFOB) nanoparticles		Non-invasive multimodal cell tracking of human pancreatic islets	Barnett et al. (2011)
Increasing fibronectin production to decrease apoptosis and therefore increase viability of transplanted islets	Calcein	Liposomes	Fibronectin mimetic peptide/α5b1 integrin expressed on pig islets	Targeted liposomes containing calcein was delivered and they shoved improved cell binding and internalized	Atchison et al. (2010)
Increasing hexokinase protease I expression, increasing insulin levels in blood and decreasing circulating glucose levels	Plasmids encoding for the genes for Human Insulin and Hexokinase I	Gas-filled Phospholipid Shell Bubbles	Insulin 1 Promoter/beta-cells/Ultrasound triggered delivery	Efficient gene delivery to pancreatic islets with the detection of transgene-encoded proteins for up to 3 weeks after transfection	Chen et al. (2006)
Increasing vascular endothelial growth factor A (VEGF-A) expression in transplanted islets to increase vessel density and graft function	Plasmid encoding for the gene for VEGF-A	Gas-filled Phospholipid Shell Bubbles	Ultrasound triggered delivery	Efficient gene delivery of VGEF-A to pancreatic islets was successful, increased vessel density, and improved graft function	Shimoda et al. (2010)
Increasing transfection efficiency and gene delivery to islet cells	Plasmid encoding for the gene for luciferase enzyme	PEI-PEG-Anti GAD Fab polymeric gene carrier	Antibody against glutamic acid decarboxylase/glutamic acid decarboxylase antigen	10-fold transfection efficiency to beta islet cells	Jeong et al. (2005)