Résumé
Controllable drug delivery is urgently pursued for cancer therapy, because conventional chemotherapy is associated with serious toxic side effects. Precisely controlled external stimuli-activated nanoparticles are promising, as selective activation of the system takes place only upon stimulation of trigger signals and only in the area of interest. Silica nanoparticles have a number of advantages such as well established synthesis methods, chemical and thermal stability, large drug loading capacity, and the ease to carry out various surface modifications. We previously showed that our mesoporous silica nanoparticle-based nanoimpellers are effective for photo-activated drug delivery. However, like other light activating nanoparticles, our nanoimpeller also employed UV/Vis light, thus limiting its medical applications due to its short wavelength and inability for deep tissue penetration. Here we report our new generation of nanoimpellers functionalized with two-photon fluorophore that has a high two photon absorption cross-section, suitable for fluorescence resonance energy transfer (FRET) to photoisomerize azobenzene moieties in the NIR region. The azobenzene residing in the porous framework allows physical entrapment of the anticancer drug camptothecin, which is then propelled out of the pores by two-photon-triggered photoisomerization, resulting in on-demand intracellular drug release. Intracellular release of molecules is dependent on light excitation powers and wavelengths, and the anticancer drug delivery inside of cells can be regulated with light excitation. TPE fluorescence imaging was performed to demonstrate the cellular uptake of the nanoimpellers. Nanoimpeller with a high energy transfer quantum yield from the fluorophore to the azobenzene moiety was able to induce cancer cell death under these TPE conditions and did not show toxicity to control cells that were shielded from light. In a similar but different design, we also synthesized nanoparticles that have nanovalves placed at the pore openings. These results suggest that our newly synthesized two-photon-activated nanoimpellers could be useful for cancer therapy because of deep tissue penetrating ability and controllability. Actual application of such light-triggered delivery system in animal models remains to be proven, but we believe this two-photon light-activated mesoporous silica nanoparticles have a broad application prospects for biomedicine.
Citation Format: Jie lu, Jonas Croissant, Jean-Olivier Jean-Olivier Durand, Tania Guardado-Alvarez, Jeffrey I. Zink, Fuyuhiko Tamanoi. Light-controllable nano-drug delivery system with deep tissue penetrating ability for cancer therapy with two-photon-triggered nanoimpellers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-9. doi:10.1158/1538-7445.AM2014-LB-9