Lipid-based Phototriggerable Platforms for Improved Delivery of Anticancer Drugs

Thursday, October 11, 2012 — Poster Session III
10:00 a.m. – Noon	Natcher Conference Center, Building 45	NCI	TECH-5

Authors

• K. Gupta
• A. Yavlovich
• J. Sine
• M. Viard
• R. Blumenthal
• A. Puri

Abstract

To date, several triggered release strategies have been explored for optimal drug delivery from nanoparitcles within defined space and time. Among these, light-sensitive liposomes present promising a system and rely on strategically designed lipids to initiate photo-triggering. The mechanism(s) of photo-triggering either include fluorophore-mediated activation of lipids, or direct intra/inter-lipid modifications. The principle criterion for clinically viable formulations, however, entails design of lipid molecules responsive to tissue-penetrating wavelengths. We have developed liposomes from a diacetylenic phospholipid, DC8,9PC (1,2 bis(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine). Our typical formulations include dipalmitoyl phosphatidylcholine, DC8,9PC, and a pegylated lipid. We load calcein (Ex/Em, 485/517 nm) or Doxorubicin (DOX, Ex/Em 490/590 nm) in the core of the liposomes. We report the following: (a) 514 nm treatment results in specific release of solutes from liposomes, and involves reactive oxygen species (ROS). (b) Laser treatment of co-cultures containing DOX-loaded liposomes and cells results in improved cytotoxicity. (c) Animal studies using the human nasopharyngeal carcinoma (KB)-Xenograft mouse model show that our formulations have similar biodistribution as compared to control (DC8,9PC minus) liposomes. Ex-vivo exposure of tumor tissue sections to irradiation by light results in disruption of liposomes. Taken together, the phototriggerable liposomes described here may provide a platform for future drug delivery applications.

back to top