Although nanomedicines have been pursued for nearly 20 years, fundamental chemical strategies that seek to optimize both the drug and drug carrier together in a concerted effort remain uncommon yet may be powerful. In this work, two block polymers and one dimeric prodrug molecule were designed to be coassembled into degradable, functional nanocarriers, where the chemistry of each component was defined to accomplish important tasks. The result is a poly(ethylene glycol) (PEG)-protected redox-responsive dimeric paclitaxel (diPTX)-loaded cationic poly(d-glucose carbonate) micelle (diPTX@CPGC). These nanostructures showed tunable sizes and surface charges and displayed controlled PTX drug release profiles in the presence of reducing agents, such as glutathione (GSH) and dithiothreitol (DTT), thereby resulting in significant selectivity for killing cancer cells over healthy cells. Compared to free PTX and diPTX, diPTX@CPGC exhibited improved tumor penetration and significant inhibition of tumor cell growth toward osteosarcoma (OS) lung metastases with minimal side effects both in vitro and in vivo, indicating the promise of diPTX@CPGC as optimized anticancer therapeutic agents for treatment of OS lung metastases.

Fundamental studies that gain an understanding of the tunability of physical properties of natural product-based polymers are vital for optimizing their performance in extensive applications. Variation of glass transition temperature (T g) was studied as a function of the side chain structure and molar mass for linear poly­(glucose carbonate)­s. A remarkable range of T g values, from 38 to 125 °C, was accomplished with six different alkyloxycarbonyl side chains. The impact of molar mass on T g was investigated for two series of polymers and discrete oligomers synthesized and fractionated with precise control over the degrees of polymerization. The T g was found to be greatly influenced by a synergistic effect of the flexibility and bulkiness of the repeating unit side chain, as well as the chain end relative free volume. This work represents an important advance in the development of glucose-based polycarbonates, as materials that possess high degrees of functionalizability to be capable of exhibiting diversified physicochemical and thermal properties by simple side chain modification.

This paper presents the synthesis and aqueous solution-state assembly of functional degradable poly(d-glucose carbonate)s, derived from renewable sources, with practical utility in biomedical applications.