Comb-like Poly( N -(2-hydroxypropyl) methacrylamide) Doxorubicin Conjugates: The Influence of Polymer Architecture and Composition on the Biological Properties

The synthesis and structure-property correlation of poly( N -(2-hydroxypropyl) methacrylamide) (PHPMA) conjugates with various architectures including random, block, branched or star-like structures and compositions have been thoroughly explored. However, related synthesis and structure-property data are still lacking for comb-like PHPMA. In this work, we report the synthesis of comb-like PHPMA copolymer-doxorubicin (DOX) conjugates with different backbone/side-chain lengths and location of drug moieties. Well-defined comb-like PHPMA-DOX conjugates are obtained via the combination of controlled radical polymerization and fractional precipitation techniques. The influences of structural factors on the biological properties such as cellular uptake, blood circulation and tumor accumulation have been investigated. Long blood circulation and efficient tumor accumulation can be achieved by proper control of the comb number, length and location of drug moieties. These facile comb-like structures possess great potentials in future theranostics for brachytherapy or surgical navigation.