(512d) Stimuli-Degradable Liposomes for Versatile Caner-Targeted Chemotherapy | AIChE

(512d) Stimuli-Degradable Liposomes for Versatile Caner-Targeted Chemotherapy

Authors 

Kim, Y. K. - Presenter, University of California, Irvine


Chemotherapy is the most predominantly used clinical method to combat against cancer but short-circulation time and non-specific accumulation of the toxic drugs in cancer as well as healthy tissues necessitate frequent administration of toxic chemoagents at high does in order to obtain desirable therapeutic efficacy, which aggravates adverse side effects in return. The concept of using nano-sized materials (i.e., nanomedicine) in achieving cancer-targeted therapy by employing enhanced permeation and retention (EPR) effect and controlled drug release has been intensively studied. Liposomes are one of the most commonly used nanocarriers for such applications. Limitations of using liposomes in cancer-targeted drug delivery include limited responsiveness to biological stimuli, lack of modification flexibility after vesicle formation, and stability in dried form.

In this study we synthesized stimuli-responsive liposomes by adding acid-degradable polymeric layers on the surface of doxorubicin-containing liposomes by interfacial polymerization. 1. At a mildly acidic pH, which is an extracellular condition frequently found in a tumor as well as in the endosome of a cell, the outer polymeric layers hydrolyze, contributing to rapid release of the encapsulated drugs (stimuli-responsiveness). 2. The polymeric outer layers also can serve as a platform for conjugation of various additional molecules (e.g., targeting and imaging moieties) without compromising the structural integrity of the liposomes (flexibility for versatile application). 3. The liposomes coated with polymeric layers can be dried and re-constituted in an aqueous solution (prolonged storage and handling).

Eosin Y, a cell membrane staining dye and photoinitiator, was embedded in the phopholipid bilayer of liposomes and polymerization of acid-degradable aminoketal methacrylamide monomers was triggered by high intensity visible light. The surface of the polymerized liposomes was further PEGylated to stealth highly cationic surface and increase circulation in vivo. Dynamic light scattering (DLS) and zeta-potential analysis proved increased sizes as polymerization and PEGylation proceeded as well as slightly negative, highly cationic, and slightly cationic surface charges of starting, polymerized, and polymerized and PEGylated liposomes, respectively. A preliminary in vivo study demonstrated that the liposomes layered with acid-degradable polymers were able to effectively eradicate subcutaneously established tumors in mice. For comparison, free doxorubicin reduced the tumor size initially but the tumor growth overrode therapeutic effects within a few days. The improved properties of the stimuli-degradable liposomes will be presented in comparison with the commercially available liposome-based drug delivery carriers, DOXIL. Additional advantages and implications of using stimuli-degradable liposomes for versatile approaches to cancer chemotherapy will also be discussed.