4.8 Article

Paclitaxel-Paclitaxel Prodrug Nanoassembly as a Versatile Nanoplatform for Combinational Cancer Therapy

Journal

ACS APPLIED MATERIALS & INTERFACES
Volume 8, Issue 49, Pages 33506-33513

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsami.6b13057

Keywords

disulfide; redox responsive; photothermal therapy; high drug loading; anticancer

Funding

  1. National Nature Science Foundation of China [81273450]
  2. Nature Science Foundation of Liaoning Province [2014020079, 2015020728]
  3. Nature Science Foundation of Guangdong Province [2016A020217017]
  4. General Project in Education Department of Liaoning Province [L2014396]

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Recently, nanomedicine without drug carriers has attracted many pharmacists' attention. A novel paclitaxel-s-s-paclitaxel (PTX-s-s-PTX) conjugate with high drug loading (similar to 78%, w/w) was synthesized by conjugating paclitaxel to paclitaxel by using disulfide linkage. The conjugate could self assemble into uniform nanoparticles (NPs) with 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR) encapsulated within the core of PTX-s-s-PTX NPs for photothermal therapy (PTT). The DiR-loaded self-assembled nanoparticles (DSNs) had a mean diameter of about 150 nm and high stability in biological condition. A disulfide bond is utilized as a redox-responsive linkage to facilitate a rapid release of paclitaxel in tumor cells. DSNs indicated significant cytotoxicity as a result of the synergetic chemo-thermal therapy. DSNs were featured with excellent advantages, including high drug loading, redox-responsive releasing behavior of paclitaxel, capability of loading photothermal agents, and combinational therapy with PTT. In such a potent nanosystem, pro drug and photothermal strategy are integrated into one system to facilitate the therapy efficiency.

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