In:
Angewandte Chemie, Wiley, Vol. 130, No. 24 ( 2018-06-11), p. 7184-7188
Abstract:
Polymeric micelle‐based drug delivery systems have dramatically improved the delivery of small molecular drugs, yet multiple challenges remain to be overcome. A polymeric nanomedicine has now been engineered that possesses an ultrahigh loading (59 %) of a glutathione (GSH)‐sensitive heterodimeric multifunctional prodrug (HDMP) to effectively co‐deliver two synergistic drugs to tumors. 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 ( 64 Cu) of HPPH enabled direct drug monitoring by fluorescence imaging and positron emission tomography (PET). Through quantitative PET imaging, HDMP significantly improves drug delivery to tumors. 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.
Type of Medium:
Online Resource
ISSN:
0044-8249
,
1521-3757
DOI:
10.1002/ange.v130.24
DOI:
10.1002/ange.201801984
Language:
English
Publisher:
Wiley
Publication Date:
2018
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