Polymeric Nanoparticles with Glutathione-Sensitive Heterodimeric Multifunctional Prodrug for In Vivo Drug Monitoring and Synergistic Cancer Therapy.

Polymeric Nanoparticles with Glutathione-Sensitive Heterodimeric Multifunctional Prodrug for In Vivo Drug Monitoring and Synergistic Cancer Therapy.
Angew Chem Int Ed Engl. 2018 Apr 06;:
Authors: Zhang F, Ni Q, Jacobson O, Cheng S, Liao A, Wang Z, He Z, Yu G, Song J, Ma Y, Niu G, Zhang L, Zhu G, Chen X
Abstract
Polymeric micelle-based drug delivery systems have dramatically improved the delivery of small molecular drugs, yet multiple challenges remain to be overcome. In this work, we engineered a polymeric nanomedicine that possesses an ultrahigh loading (59%) of a glutathione (GSH)-sensitive heterodimeric multifunctional prodrug (HDMP) to effectively co-deliver two synergistic drugs to tumor. Specifically, an HDMP comprising of chemotherapeutic camptothecin (CPT) and photosensitizer 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-α (HPPH), was conjugated via a GSH-cleavable linkage. The intrinsic fluorogenicity and label-free radio-chelation (64Cu) of HPPH enabled direct drug monitoring by fluorescence imaging and positron emission tomography (PET). Through quantitative PET imaging, we demonstrated that HDMP significantly improves drug delivery to tumor. The high synergistic therapeutic efficacy of HDMP-loaded NPs highlights the rational design of HDMP, and presents exciting opportunities for polymer NP-based drug delivery.
PMID: 29624828 [PubMed - as supplied by publisher]

Source: Angewandte Chemie - April 6, 2018 Category: Chemistry Authors: Zhang F, Ni Q, Jacobson O, Cheng S, Liao A, Wang Z, He Z, Yu G, Song J, Ma Y, Niu G, Zhang L, Zhu G, Chen X Tags: Angew Chem Int Ed Engl Source Type: research