Nonconventional fluorescent Carvone-Derived polyesters as a sustainable platform for PROTAC nanotheranostics

• A renewable carvone-derived polyester enables multifunctional nanotheranostic design. • Intrinsic cluster-based fluorescence allows dye-free real-time nanoparticle tracking. • The polymer matrix efficiently encapsulates a structurally complex protein degrader while preserving activity. • Material structure, optical function, and therapeutic performance are integrated in a single sustainable platform. Nanotechnology offers a powerful strategy to improve the therapeutic index of anticancer agents by enhancing efficacy and reducing systemic toxicity. Here, we describe a novel application of a carvone-derived polyester as a functional platform for nanotheranostics. This biomass-based copolyester, synthesized via ring-opening copolymerization of a carvone monoepoxide and phthalic anhydride, exhibits nonconventional fluorescence originating from cluster-triggered and aggregation-induced emission. Such intrinsic luminescence eliminates the need for external dyes, enabling real-time optical tracking of nanoparticle (NP) behavior. As a stringent test case, we selected THAL-SNS-032, a clinically relevant PROTAC degrader of CDK9 with potent antitumor activity but dose-limiting systemic toxicity. Encapsulation within the carvone-based NPs preserves its cytotoxic potency while improving biocompatibility and colloidal stability. Fluorescence Lifetime Imaging Microscopy confirms efficient cellular uptake and time-dependent NP disassembly, validating the material’s inherent theranostic capability. This work introduces a new class of nonconventional fluorescent, biomass-derived copolyesters as sustainable platforms that integrate drug delivery and optical monitoring within a single renewable material framework, paving the way toward next-generation PROTAC nanotheranostics.