928838-78-2Relevant academic research and scientific papers
ACID-SENSITIVE LINKERS FOR DRUG DELIVERY
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Page/Page column 9, (2011/04/14)
The invention is in general directed to acid-sensitive linkers, and methods of use thereof, such as, for example, in drug delivery methods.
PH-Sensitive, N-ethoxybenzylimidazole (NEBI) bifunctional crosslinkers enable triggered release of therapeutics from drug delivery carriers
Luong, Alice,Issarapanichkit, Tawny,Kong, Seong Deok,Fong, Rina,Yang, Jerry
supporting information; experimental part, p. 5105 - 5109 (2010/12/25)
This paper presents a pH-sensitive bifunctional crosslinker that enables facile conjugation of small molecule therapeutics to macromolecular carriers for use in drug delivery systems. This N-ethoxybenzylimidazole (NEBI) bifunctional crosslinker was designed to exploit mildly acidic, subcellular environments to trigger the release of therapeutics upon internalization in cells. We demonstrate that an analog of doxorubicin (a representative example of an anticancer therapeutic) conjugated to human serum albumin (HSA, a representative example of a macromolecular carrier) via this NEBI crosslinker can internalize and localize into acidic lysosomes of ovarian cancer cells. Fluorescence imaging and cell viability studies demonstrate that the HSA-NEBI-doxorubicin conjugate exhibited improved uptake and cytotoxic activity compared to the unconjugated doxorubicin analog. The pH-sensitive NEBI group was also shown to be relatively stable to biologically-relevant metal Lewis acids and to serum proteins, supporting that these bifunctional crosslinkers may be useful for constructing drug delivery systems that will be stable in biological fluids such as blood.
