4.7 Article

In Vivo Bioorthogonal Chemistry Enables Local Hydrogel and Systemic Pro-Drug To Treat Soft Tissue Sarcoma

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ACS CENTRAL SCIENCE
卷 2, 期 7, 页码 476-482

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AMER CHEMICAL SOC
DOI: 10.1021/acscentsci.6b00150

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  1. Directorate For Engineering [1549133] Funding Source: National Science Foundation
  2. Div Of Industrial Innovation & Partnersh [1549133] Funding Source: National Science Foundation

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The ability to activate drugs only at desired locations avoiding systemic immunosuppression and other dose limiting toxicities is highly desirable. Here we present a new approach, named local drug activation, that uses bioorthogonal chemistry to concentrate and activate systemic small molecules at a location of choice. This method is independent of endogenous cellular or environmental markers and only depends on the presence of a preimplanted biomaterial near a desired site (e.g., tumor). We demonstrate the clear therapeutic benefit with minimal side effects of this approach in mice over systemic therapy using a doxorubicin prodrug against xenograft tumors of a type of soft tissue sarcoma (HT1080).

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