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Merck

Renal Clearable Theranostic Nanoplatforms for Gastrointestinal Stromal Tumors.

Advanced materials (Deerfield Beach, Fla.) (2019-12-20)
Homan Kang, Wesley R Stiles, Yoonji Baek, Shinsuke Nomura, Kai Bao, Shuang Hu, G Kate Park, Min Joo Jo, Hoseok I, Jean-Luc Coll, Brian P Rubin, Hak Soo Choi
ANOTACE

Advances in molecular imaging modalities have accelerated the diagnosis and treatment of human diseases. However, tumors less than 1 cm in size still remain difficult to localize by conventional means because of the difficulty in specific targeting/delivery to the tumor site. Furthermore, high nonspecific uptake in the major organs and persistent background retention results in low tumor-to-background ratio. The targeting and therapy of gastrointestinal stromal tumors (GIST) using nonsticky and renal clearable theranostic nanoparticles (a.k.a. H-Dots) are demonstrated. H-Dots not only target GIST for image-guided surgery, but also tailor the fate of anticancer drugs such as imatinib (IM) to the tumor site resulting in efficient treatment of unresectable GIST. In addition, H-Dots can monitor targetability, pharmacokinetics, and drug delivery, while also showing therapeutic efficacy in GIST-bearing xenograft mice following surgical resection. More importantly, IM loaded H-Dots exhibit lower uptake into the immune system, improved tumor selectivity, and increased tumor suppression compared to free IM, which accumulates in the spleen/liver. Precisely designed H-Dots can be used as a promising theranostic nanoplatform that can potentially reduce the side effects of conventional chemotherapies.

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Sigma-Aldrich
Dess-Martin periodinane, 97%
Sigma-Aldrich
Imatinib
Sigma-Aldrich
Dipyrrolidino(N-succinimidyloxy)carbenium hexafluorophosphate, ≥98.0% (CHN)