(590c) Cancer-Targeted Chemotherapy Via Stimuli-Responsive and Externally Triggered Drug Release From Acid-Degradable Liposomes | AIChE

(590c) Cancer-Targeted Chemotherapy Via Stimuli-Responsive and Externally Triggered Drug Release From Acid-Degradable Liposomes

Authors 

Kim, Y. K. - Presenter, University of California, Irvine
Wang, J. - Presenter, University of California, Irvine
Kwon, Y. J. - Presenter, University of California, Irvine


In order to obtain high therapeutic efficacy with minimally adverse side effects via enhanced permeation and retention (EPR) effect, nanosized drug carriers, called nanomedicine, have been popularly explored for targeted cancer chemotherapy. Liposomes are among the first and most popularly utilized drug carriers because they are biocompatible and biodegradable as well as carrying both hydrophilic and hydrophobic drugs. Ideal cancer-targeted drug delivery requires selective drug release by cancer-specific stimuli in a target tissue. In this study, acid-degradable polymers were incorporated onto the surface of doxorubicin (DOX)-carrying liposomes. It was hypothesized that the polymeric layer enforces liposome's structural stability during circulation, followed by disrupted liposomal membrane integrity in the mildly acidic environment in a tumor tissue, resulting in selective drug release. This stimuli-responsive drug release was also hypothesized to be accelerated by external physical triggers. Dynamic light scattering (DLS) and zeta-potential analyses proved efficient incorporation of polymeric layers on the DOX-liposomes, indicated by size increases and surface charge changes. Loss of structural integrity of the acid-degradable liposomes under an acidic condition was observed by transmission electron microscopy (TEM). Clear pH-dependent profiles of drug release and efficient intracellular drug release from the acidic endosomes (observed by confocal microscopy) demonstrated that the design goals for the stimuli-responsive liposomes were met. Comprehensive in vivo study showed that the acid-degradable liposomes effectively eradicated a model tumor. An external force dramatically improves drug release from destabilized acid-degradable liposomes drug release. The novel drug nanocarriers are easily hybridized with imaging probes for combined imaging and therapy.

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