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pH‐Switch Nanoprecipitation of Polymeric Nanoparticles for Multimodal Cancer Targeting and Intracellular Triggered Delivery of Doxorubicin
Author(s) -
HerranzBlanco Bárbara,
Shahbazi MohammadAli,
Correia Alexandra R.,
Balasubramanian Vimalkumar,
Kohout Tomáš,
Hirvonen Jouni,
Santos Hélder A.
Publication year - 2016
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201600160
Subject(s) - doxorubicin , intracellular , conjugate , cytotoxicity , drug delivery , cancer cell , nanoparticle , chemistry , materials science , biophysics , internalization , nanotechnology , cancer , biochemistry , cell , chemotherapy , in vitro , medicine , biology , mathematical analysis , surgery , mathematics
Theranostic nanoparticles are emerging as potent tools for noninvasive diagnosis, treatment, and monitoring of solid tumors. Herein, an advanced targeted and multistimuli responsive theranostic platform is presented for the intracellular triggered delivery of doxorubicin. The system consists of a polymeric‐drug conjugate solid nanoparticle containing encapsulated superparamagnetic iron oxide nanoparticles (IO@PNP) and decorated with a tumor homing peptide, iRGD. The production of this nanosystem is based on a pH‐switch nanoprecipitation method in organic‐free solvents, making it ideal for biomedical applications. The nanosystem shows sufficient magnetization saturation for magnetically guided therapy along with reduced cytotoxicity and hemolytic effects. IO@PNP are largely internalized by endothelial and metastatic cancer cells and iRGD decorated IO@PNP moderately enhance their internalization into endothelial cells, while no enhancement is found for the metastatic cancer cells. Poly(ethylene glycol)‐ block ‐poly(histidine) with pH‐responsive and proton‐sponge properties promotes prompt lysosomal escape once the nanoparticles are endocyted. In addition, the polymer‐doxorubicin conjugate solid nanoparticles show both intracellular lysosomal escape and efficient translocation of doxorubicin to the nuclei of the cells via cleavage of the amide bond. Overall, IO@PNP‐doxorubicin and the iRGD decorated counterpart demonstrate to enhance the toxicity of doxorubicin in cancer cells by improving the intracellular delivery of the drug carried in the IO@PNP.