Polymeric Encapsulation of a Ruthenium Polypyridine Complex for Tumor Targeted One- and Two-Photon Photodynamic Therapy

Abstract

Photodynamic therapy is a medical technique, which is gaining increasing attention to treat various types of cancer. Among the investigated classes of photosensitizers, the use of Ru(II) polypyridine complexes is gaining momentum. However, the currently investigated compounds generally show poor cancer cell selectivity. As a consequence, high drug doses are needed, which can cause side effects. To overcome this limitation, there is a need for the development of a suitable drug delivery system to increase the amount of PS delivered to the tumor. Herein, we report on the encapsulation of a promising Ru(II) polypyridyl complex into polymeric nanoparticles with terminal biotin groups. Thanks to this design, the particles showed much higher selectivity for cancer cells in comparison to non-cancerous cells in a 2D monolayer and 3D multicellular tumor spheroid model. As a highlight, upon intravenous injection of an identical amount of the Ru(II) polypyridine complex, an improved accumulation inside an adenocarcinomic human alveolar basal epithelial tumor of a mouse by a factor of 8.7 compared to the Ru complex itself was determined. The nanoparticles were found to have a high phototoxic effect upon 1-photon (500 nm) or 2-photon (800 nm) excitation with an eradication of an adenocarcinomic human alveolar basal epithelial tumor inside a mouse. Overall, this work describes, to the best of our knowledge, the first in vivo study demonstrating the cancer cell selectivity of a very promising Ru(II)-based PDT photosensitizer encapsulated into polymeric nanoparticles with terminal biotin groups.

Ru(II) Polypyridine Complex-Functionalized Mesoporous Silica Nanoparticles as Photosensitizers for Cancer Targeted Photodynamic Therapy

“…The absorption and emission spectra were recorded, lifetime and singlet oxygen measurements were performed as previously described. 37,39 Cell culture Human normal lung fibroblast (MRC-5) cells were cultured in DMEM/F10 media containing 0.65 mg/L folic acid. The human ovarian carcinoma (A2780) cells were cultured in RPMI 1640 media containing 1.00 mg/L folic acid.…”

Klinische Entwicklung von Metallkomplexen als Photosensibilisatoren für die photodynamische Therapie von Krebs

“…[54] Tr otz jüngster Verbesserungen bei der Entwicklung von Lichtquellen fürM ulti-Photonen-Anregungen und PS mit einer verbesserten Zwei-Photonen-Absorption wurde bisher noch keine Verbindung in klinischen Studien untersucht. Interaktion einer tumoraffinen funktionellen Gruppen genutzt, wie sie beispielsweise in Antikçrpern, [55] Oligonukleotiden, [56] Oligosacchariden, [57] Vitaminen, [58] Signalpeptiden [59] oder Proteinen [60] zu finden ist. Als alternative Strategie im Rahmen eines passiven Tu mortransportes werden gezielt die durchlässigen Gefäße und lymphatischen Eigenschaften des Tu morgewebes unter Ausnutzung des EPR-Effekts (Enhanced Permeability and Retention) genutzt.…”

CO/light dual-activatable Ru(ii)-conjugated oligomer agent for lysosome-targeted multimodal cancer therapeutics

“…Meanwhile, the release of Ru(II) anticancer agents also suppress cancer cell growth as an anticancer metal drugs. [39][40][41] The significant anti-cancer effect was realized by the multimodal therapeutics of physical disruption/PDT/chemotherapy. This study reports a cationic conjugated oligomer-based dual-activatable systems for lysosome-targeted multimodal cancer treatment together with fluorescent monitoring drug delivery, which paved the way to develop more secure, effective and intelligent therapeutic potential drug.…”