Matrix metalloproteinase-sensitive size-shrinkable nanoparticles for deep XXXX penetration and pH triggered @entity632 release.

@entity632 @entity5 @entity19 @entity5780 @entity3105 @entity970 @entity968
UNASSIGNED: Nanocarriers are widely used for delivering drugs to @entity5 and are progressing in a stable trend. The enhanced permeability and retention (EPR) effect has been a key rationale for the development of stimulus-responsive nanocarriers to @entity5 . In this study, we developed a kind of novel nanocarrier, G-AuNPs- @entity3105 - @entity970 , which was constructed with shrinkable gelatin nanoparticles coated, @entity632 ( @entity3105 ) tethered gold nanoparticles and long chain @entity968 ( @entity970 ). The particle size of G-AuNPs- @entity3105 - @entity970 was 186.5  nm with a zeta potential of  -4.21  mV and the @entity3105 loading capacity was 9.22%. In  vitro, the G-AuNPs- @entity3105 - @entity970 could be degraded by @entity5780 proteins with a size shrink from 186.5  nm to 59.3  nm. The release of @entity3105 from G-AuNPs- @entity3105 - @entity970 was in a pH- and time-dependent manner. At pH 5.0, the release of @entity3105 was much quicker than that at high pH value and the cumulative release rate of @entity3105 from G-AuNPs- @entity3105 - @entity970 was approach 90.9%. Cellular uptake demonstrated that G-AuNPs- @entity3105 - @entity970 could be internalized via the endosome-mediated pathway. @entity5 spheroid penetration and collagen gel diffusion showed G-AuNPs- @entity3105 - @entity970 with pre-incubation with @entity5780 could significantly enhance its penetrating efficiency. In  vivo and ex  vivo imaging exhibit that G-AuNPs- @entity3105 - @entity970 could distribute into 4T1 and B16F10 @entity5 at a highest intensity. Correspondingly, 4T1 and B16F10 @entity5 bearing @entity19 treated with G-AuNPs- @entity3105 - @entity970 displayed the @entity5 growth rate. In summary, the @entity5 microenvironment sensitive size-shrinkable G-AuNPs- @entity3105 - @entity970 could deliver into deep @entity5 region and then release @entity3105 , resulting in a best anti- @entity5 effect.
