pH-Sensitive morphological transitions in polymeric tadpole assemblies for programmed tumor therapy


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Abstract

Ultrafine single-chain tadpole polymers (SCTPs), containing an intrachain crosslinked globule and a pH-sensitive linear polymer chain, have been synthesized. Self-assembly of these polymers depends on the linear block length and the pH, at which the polymer is assembled. Although the SCTPs themselves exhibit a size that is consistent with a single-chain species, the self-assembled SCTPs were found to be substantially larger. Since the transition between these two structures is reversibly dependent on pH, we explored the possibility of utilizing these assemblies to achieve deep tissue penetration in tumors. Our results indicate that there is indeed a pH-dependent deep tissue penetration in ex vivo tumor multicellular spheroids. Moreover, the multi-tadpole assemblies (MTAs) can stably encapsulate hydrophobic molecules, which have been used to encapsulate paclitaxel (PTX). These PTX/MTAs show excellent therapeutic efficacy and biosafety in 4 T1 xenograft mouse models. The innovative multi-compartment aggregates are able to fulfill structure-related function transitions with the variation of microenvironment, which has potential to extremely enrich the design of sophisticated biological agents.

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