pH-sensitive fluorescent hyaluronic acid nanogels for tumor-targeting and controlled delivery of doxorubicin and nitric oxide

다국어 초록 (Multilingual Abstract)

<P><B>Abstract</B></P> <P>We herein report the development of a tumor-targeting, pH-responsive, and enzymatically degradable crosslinked fluorescent nanogel (F-nanogel) of boronic acid-conjugated lactose modified-chitosan (chitlac-BOH) and dopamine- and nitric oxide-conjugated partially carbonized hyaluronic acid [NO/DA-FNP(HA)] for doxorubicin (DOX) loading. In DOX-loaded F-nanogels, DOX and NO were released owing to the pH-dependent cleavage of boronic acid-catechol diol crosslinking and the enzymatic activity of hyaluronidase (HAase). The combination of both pH and HAase in cancer cells selectively regulate the release of DOX and NO by enzymatic activity. We further confirmed the specificity of this drug delivery carrier to the desired location by using confocal imaging, while NO release by HAase was confirmed via diaminofluorescein-2 diacetate assay. This nanoparticle system utilized tumor-targeting HA to deliver DOX and NO within cancer cells, while tracking is performed via bio-imaging based on fluorescent HA. Finally, the F-nanogel(DOX) can be broadly tested as a medical material with a broad range of potential applicability for monitoring cancer and the incorporation of drug and NO co-delivery systems.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Tumor-targeted, pH and enzymatically degradable fluorescent nanogel were designed. </LI> <LI> Our designed system show excellent DOX and NO release <I>in vitro</I> of cancer cell. </LI> <LI> Fluorescent nanogel allows great specificity of cancer imaging and chemotherapy. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>