Table 1.

Overview of the reactive polymers that have been used as templates for the post-modification-based optimization of therapeutic delivery polymers.

Category of reactive polymers	Representative reactive polymers	Compounds for post- modification	Conditions and results of post- modification			Polymer library size	Properties of functional polymers synthesized by post-modification			Therapeutic payloads	Ref.
			Need of catalyst or co- reagent	Reaction byproduct yielded	Need of additional purificatio n steps		Well- defined chemical structure	Cost of polymer and synthesis	Biocomp atibility/ biodegra dability
N-Hydroxysuccinimide-functionalized polyacrylates	Poly(N-methacryloxysuccinimide)	Primary or secondary amines	No	Yes	Yes	168	Fair	Low	Fair	DNA	[29]
Azlactone-functionalized polymers	Poly(2-vinyl-4,4-dimethylazlactone)	Primary amines	No	No	Yes†	12	Fair	Low	Unknow	DNA	[27]
Hydrazide-functionalized macromolecules	Poly(acryloyl hydrazide)	Aldehydes	No	No	No	10	Fair	Low	Unknow	siRNA	[28]
	Hydrazone-modulated peptide	Aldehydes	No	No	No	28	Yes	High	Good	DNA	[43]
Natural polysaccharides and derivatives	Hyaluronic acid	Amines	Yes	No	Yes	14	No	Low	Good	siRNA	[35]
	O-pentynyl dextran	Azides	Yes	No	Yes	8	No	Low	Good	Anticancer drugs	[36]
Oligo(amino acid)s-based platforms	Hydrazone-modulated peptide	Aldehydes	No	No	No	28	Yes	High	Good	DNA	[43]
	Telodendrimer	Carboxylic acids	Yes	No	Yes	24, 7	Yes	High	Good	Doxorubicin, insulin	[17], [31]

^†In ref. [27], the additional purification step was performed to remove the excess, unreacted small-molecule reactants. However, purification steps will become unnecessary if equivalent units of small-molecule reactants are used for post-modification, which will enable high-throughput polymer synthesis for therapeutic delivery.