Photo-triggered Drug Release Systems

• Applicants: Professor Dr. Norbert Jux; Professorin Dr. Beate Röder
• Subject Area: Physical Chemistry of Molecules, Liquids and Interfaces, Biophysical Chemistry ; Biological and Biomimetic Chemistry
• Term: from 2010 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 161707834

Based on the apparent lack of reliable methods for selective drug accumulation in tumors, we will establish a new targeting strategy based on the Enhanced Retention and Permeability (EPR) effect. For this purpose, a high-weight Carrier System (CS) which consists of co-block polymer micelles containing Drug Delivery Conjugates (DDC) will be developed. The micellar encapsulation of DDCs together with their special design will prevent the release of the drug molecules prior to photosensitized activation. Lysosomal enzymes will destroy the micelles and liberate the DDCs. The DDC will possess a large number of drugs, i.e., photosensitizers (PS). These are connected to a dendritic core, preventing any significant photoactivity due to dye-dye interactions. Specially designed indirectly photo-cleavable scission units will allow controlled drug-release. Light absorbed by the PS will cause singlet oxygen (1O2) generation in small amounts which attacks the scission units. Drug separation from the DDCs will be achieved. The liberated drug molecules will then act independently and generate 1O2 in a high amount leading to cell death. Our concept allows targeted therapy together with a strongly light triggered drug release making the therapy independent of specific cell parameters such as pH. Given the modular approach to the DDC, chemotherapeutics can also be attached und thus, combined therapies are envisionable.

• DFG Programme: Research Grants