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Delaying Anticancer Drug Delivery by Self‐Assembly and Branching Effects of Minimalist Dendron–Drug Conjugates
Author(s) -
Correard Florian,
Roy Myriam,
Terrasson Vincent,
Braguer Diane,
Estève MarieAnne,
Gingras Marc
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201801092
Subject(s) - dendrimer , intracellular , chemistry , conjugate , dynamic light scattering , drug delivery , biophysics , branching (polymer chemistry) , spheroid , peg ratio , succinic anhydride , paclitaxel , nanoparticle , drug , conjugated system , combinatorial chemistry , nanotechnology , biochemistry , materials science , pharmacology , organic chemistry , cancer , biology , in vitro , mathematical analysis , genetics , mathematics , finance , economics , polymer
Self‐assembly of a covalently‐bound lipophilic drug to a dendronic scaffold for making organic nanoparticles is reported as a proof of concept in nanovectorization. A minimalist structural approach with a small PEG‐dendron conjugated to paclitaxel (PTX), incorporating safe succinic and gallic acids, is efficient to provide the expected anticancer bioactivity, but also significantly retards and targets intracellular delivery of PTX in 2D and 3D lung cancer cell cultures. A branching effect of dendrons is crucial, when compared to linear PTX conjugates. Transmission electron microscopy (TEM) and dynamic light‐scattering (DLS) studies indicate the formation of stable, low‐disperse nanoparticles at 10 −5 m in H 2 0, which could also be responsible for the biological effects. An ultrasensitive LC‐MS/MS method was used for the determination of intracellular PTX concentration over time, along with the survival rates of cancer cells. Similarly, cell survival assays were successfully correlated to a 3D cell culture with spheroids for mimicking tumors, when treated with PTX conjugates. Our work opens the way to a full evaluation program required for new chemical entities.