Table 1.

Summary of ligands used to functionalize polymersomes for targeted delivery.

Model	Target receptor	Ligand	Chemistry used for conjugation	Enhancement	Reference
Small molecule metabolites
Breast cancer	Folate receptor	Folic acid	Coupling of aminated folic acid and PLGA-NHS	1.7-fold higher uptake	[81]
Liver cancer	Folate receptor	Folic acid	Physical conjugation	3.5-fold lower IC50	[82]
Cervical cancer	Folate receptor	Folic acid	Amino group of copolymer and folic acid	Halved tumor volume	[83]
Bacteria	Concanavalin A	Glucose	Displacement of pentafluorophenol by β-D-glucosyloxyethylamine	8-fold higher binding	[84]
Bacteria	Concanavalin A	Glucose	Atom transfer radical polymerization of methacrylated-glucose monomers	60% increased concanavalin A binding	[85]
Peptides
Blood brain barrier	Low-density protein receptor-related protein 1	Angiopep-2	Maleimide terminated polymer with cysteine-terminated peptide	3 to 4-fold higher uptake in the brain and spinal cord	[86]
Blood brain barrier	GM1 and GT1b receptors	G23	Maleimide functionalized polymer with cysteine bearing peptide	4-fold increment in transcytosed polymersomes	[87]
Lung cancer	α3β1 integrins	cyclic peptide cNGQGEQc	N-hydroxysuccinimide-functionalized polymer with amino-functionalized peptide	3-fold lower IC50	[88]
Lung cancer	α3β1 integrins	cyclic peptide cNGQGEQc	N-hydroxysuccinimide-functionalized polymer with amino-functionalized peptide	Increased median survival time from 30 to 54 days	[89]
Dendritic cells	Cellular membrane	Tat	Succinimide-terminated polymer with amino-functionalized peptide	2 h reduction in time to obtain half-maximal fluorescent intensity; 7-fold increase maximal fluorescent intensity	[90]
Aptamers
Lung cancer	Epithelial cell-adhesion molecule	19-mer EpCAM RNA aptamer	Carboxylic acid-functionalized polymer with amine-terminated aptamer	Halved tumor volume	[91]
Protein ligands
Blood brain barrier	Low-density lipoprotein receptor family	Lactoferrin	Maleimide-functionalized polymers with sulfhydrated-lactoferrin	2-fold increase in brain permeability surface area product	[92]
Blood brain barrier	Transferrin receptor	Transferrin	Maleimide-functionalized polymers with sulfhydrated-transferrin	2.3-fold increase in brain uptake	[93]
Antibodies
Breast cancer	Human Epidermal Growth Factor Receptor-2	Trastuzumab	Maleimide-functionalized polymer with thiol-derivatized trastuzumab	2-fold increase in signal-to-noise ratio	[94]
Inflamed epithelial	Endothelial cell adhesion molecules ICAM-1	Anti-ICAM1	Neutravidin-coated polymersomes with biotinylated antibodies	7.5-fold increase in binding rate to inflamed versus uninflamed cells	[95]
Blood brain barrier	Transferrin receptor	Transferrin receptor monoclonal antibodies	Maleimide-functionalized polymer with thiol-derivatized antibodies	2.6-fold increase in accumulation in the brain	[96]