A major challenge in cancer treatment is the development of effective tumor-specific therapeutic methods that have minimal side effects. Recently, a photodynamic therapy (PDT) technique using activatable photosensitizers (aPSs) has shown great potential for cancer-specific treatment. Here, we develop a sequential protein-responsive aPS (PcC4-MSN-O1) that is based on zinc(II) phthalocyanine derivative (PcC4)-entrapped mesoporous silica nanoparticles (MSNs) and a wrapping DNA (O1) as a biogate. Inside the nanostructure of PcC4-MSN-O1, PcC4 shows self-quenching photoactivity. However, when PcC4-MSN-O1 sequentially reacts with telomerase and albumin, its photoactivity is dramatically turned on. Therefore, PcC4-MSN-O1 displays selective phototoxicity against cancer cells (e.g., HeLa) over normal cells (e.g., HEK-293). Following systemic PcC4-MSN-O1 administration, there is an obvious accumulation in HeLa tumors of xenograft-bearing mice, and laser irradiation clearly induces the inhibition of tumor growth. Moreover, the time-modulated activation process in tumors and the relatively fast excretion of PcC4-MSN-O1 indicate its advantages in reducing potential side effects.
Bibliographical noteFunding Information:
X.-B.Z. thanks the National Natural Science Foundation of China (Grant No. 21521063) and the Science and Technology Project of Hunan Province (2016RS2009 and 2016WK2002).
X.-B.Z. thanks the National Natural Science Foundation of China (Grant No. 21521063) and the Science and Technology Project of Hunan Province (2016RS2009 and 2016WK2002). J.Y. thanks the National Research Foundation of Korea (NRF), which was funded by the Korean government (MSIP) (Grant No. 2012R1A3A2048814). H.F. thanks the National Postdoctoral Program for Innovative Talents (BX201700072). K.T.N. thanks the Korea Mouse Phenotyping Project (NRF-2016M3A9D5A01952416) of the National Research Foundation.
© 2019 American Chemical Society.
All Science Journal Classification (ASJC) codes
- Materials Science(all)
- Physics and Astronomy(all)