Accelerated Polymer–Polymer Click Conjugation by Freeze–Thaw Treatment

Herein, we report a unique technique to accelerate polymer–SNA conjugation based on copper-free click chemistry: gradual freeze–thawing of the reaction solution substantially increases the conjugation rate possibly because of the reactant concentration at the microenvironment scale. This technique was applied to the conjugation between a small interfering RNA (siRNA) and PEG in an aqueous buffer at/below room temperature.