Encapsulating pH-Responsive Doxorubicin-Phthalocyanine Conjugates in Mesoporous Silica Nanoparticles for Combined Photodynamic Therapy and Controlled Chemotherapy.
Roy C H WongDennis K P NgWing-Ping FongPui-Chi LoPublished in: Chemistry (Weinheim an der Bergstrasse, Germany) (2017)
Doxorubicin (Dox) was conjugated to a zinc(II) phthalocyanine (ZnPc) through an acid-cleavable hydrazone linker. This azido-containing conjugate was then anchored to the nanochannels of an alkyne-modified mesoporous silica nanoparticle (MSN) system via copper(I)-catalyzed azide-alkyne cycloaddition. An analogous nanosystem was also prepared by immobilization of a hydrazine-substituted ZnPc to the MSN followed by coupling with Dox. The release of Dox under acidic conditions was studied in phosphate-buffered saline. After internalization into human hepatocellular carcinoma HepG2 cells, these nanoparticles showed fluorescence not only for ZnPc, but also for Dox, suggesting that release of Dox was triggered by the acidic intracellular environment. The chemocytotoxic Dox together with singlet oxygen generated upon irradiation on the encapsulated ZnPc in these MSNs could kill the cells effectively. A synergistic cytotoxicity was suggested by a less-than-unity combination index. These nanoparticles function as both nanophotosensitizers for photodynamic therapy and as nanoplatforms for pH-controlled drug release.
Keyphrases
- photodynamic therapy
- cancer therapy
- drug release
- drug delivery
- fluorescence imaging
- induced apoptosis
- ionic liquid
- room temperature
- endothelial cells
- squamous cell carcinoma
- oxide nanoparticles
- oxidative stress
- radiation therapy
- single molecule
- signaling pathway
- cell proliferation
- walled carbon nanotubes
- energy transfer
- pi k akt