Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 7, Issue 17, Pages 9287-9296Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.5b02297
Keywords
dual-targeting; mitochondria; photodynamic therapy; drug delivery; graphene oxide
Funding
- NSFC [21474031, 21174040, 21025415]
- National Key Basic Research Program of China [2013CB834702]
- Fundamental Research Funds for the Central Universities, SCUT
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Photodynamic therapy (PDT) has been recognized as a valuable treatment option for localized cancers. Herein, we demonstrate a cellular and subcellular targeted strategy to facilitate PDT efficacy. The PDT system was fabricated by incorporating a cationic porphyrin derivative (MitoTPP),onto the polyethylene glycol (PEG)-functionalized and folic acid-modified nanographene oxide (NGO). For this PDT system, NGO serves as the carrier for MitoTPP as well as the quencher for MitoTPP's fluorescence and singlet oxygen (O-1(2)) generation. Attaching a hydrophobic cation to the photosensitizer ensures its release from NGO at lower pH values as well as its mitochondria-targeting capability. Laser confocal microscope experiments demonstrate that this dual-targeted nanosystem could preferably enter the cancer cells overexpressed with folate receptor, and release its cargo MitoTPP, which subsequently accumulates in mitochondria. Upon light irradiation, the released MitoTPP molecules generate singlet oxygen and cause oxidant damage to the mitochondria. Cell viability assays suggest that the dual-targeted nanohybrids exhibit much higher,cytotoxicity toward the FR-positive cells.
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