Self-Assembled Porphyrin Nanodiscs with Structure-Dependent Activation for Phototherapy and Photodiagnostic Applications
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- 作者：Kenneth K. Ng ; Jonathan F. Lovell ; Ali Vedadi ; Taraneh Hajian ; Gang Zheng
- 刊名：ACS Nano
- 出版年：2013
- 出版时间：April 23, 2013
- 年：2013
- 卷：7
- 期：4
- 页码：3484-3490
- 全文大小：466K
- 年卷期：v.7,no.4(April 23, 2013)
- ISSN：1936-086X
文摘
The abilities to deliver and subsequently activate a therapeutic at the intended site of action are two important challenges in the synthesis of novel nanoparticles. Poor tumor permeability as a result of a dense microenvironment can impede the delivery of nanoparticles to the site of action. The design of a sub-40 nm activatable porphyrin nanodisc, based on protein-induced lipid constriction, is described. The biophotonic nanoparticle, self-assembled from aggregated porphyrin鈥搇ipid, is stabilized by an amphipathic alpha helical protein and becomes photoactive when its structure is perturbed. Enzymatic cleavage of the constricting protein leads to conversion of the particle from a disc- to a vesicle-shaped structure and provides further evidence that the apolipoprotein serves a functional role on the nanodisc. Fluorescence measurements of these nanodiscs in a detergent show that fluorescence is over 99% quenched in the intact state with a 12-fold increase in singlet oxygen generation upon disruption. Cellular fluorescence unquenching and dose-dependent phototoxicity demonstrate that these nanodiscs can be internalized and unquenched intracellularly. Finally, nanodiscs were found to display a 5-fold increase in diffusion coefficient when compared with the protein-free control ((3.5 卤 0.1) 脳 10鈥?vs (0.7 卤 0.03) 脳 10鈥? cm2 s鈥?). The ability to incorporate large amounts of photosensitizer drugs into its compact structure allows for phototherapeutic action, fluorescence diagnostic applications, and the potential to effectively deliver photosensitizers deep into poorly permeable tumors.