Understanding the interactions between porphyrin-containing photosensitizers and polymer-coated nanoparticles in model biological environments
Gold nanostructure, Drug delivery, PEG coating, Controlled release
Non-covalent incorporation of hydrophobic drugs into polymeric systems is a commonly-used strategy for drug delivery because non-covalent interactions minimize modification of the drug molecules whose efficacy is retained upon release. The behaviors of the drug–polymer delivery system in the biological environments it encounters will affect the efficacy of treatment. In this report, we have investigated the interaction between a hydrophobic drug and its encapsulating polymer in model biological environments using a photosensitizer encapsulated in a polymer-coated nanoparticle system. The photosensitizer, 3-(1′-hexyloxyethyl)-3-devinylpyropheophorbide-a (HPPH), was non-covalently incorporated to the poly(ethylene glycol) (PEG) layer coated on Au nanocages (AuNCs) to yield AuNC–HPPH complexes. The non-covalent binding was characterized by Scatchard analysis, fluorescence lifetime, and Raman experiments. The dissociation constant between PEG and HPPH was found to be ∼35 μM with a maximum loading of ∼2.5 × 105 HPPHs/AuNC. The release was studied in serum-mimetic environment and in vesicles that model human cell membranes. The rate of protein-mediated drug release decreased when using a negatively-charged or cross-linked terminus of the surface-modified PEG. Furthermore, the photothermal effect of AuNCs can initiate burst release, and thus allow control of the release kinetics, demonstrating on-demand drug release. This study provides insights regarding the actions and release kinetics of non-covalent drug delivery systems in biological environments.
Jenkins, S. V., Srivatsan, A., Reynolds, K. Y., Gao, F., Zhang, Y., Heyes, C. D., . . . Chen, J. (2016). Understanding the interactions between porphyrin-containing photosensitizers and polymer-coated nanoparticles in model biological environments. Journa