Light-induced inhibition of intracellular molecules holds great promise for a selective treatment of cancer and other diseases. Challenges for the targeting of intracellular proteins are the synthesis of effective photoimmuno-conjugates and their functional delivery inside living cells. In earlier studies we have shown, that photodynamic inactivation of the nuclear Ki-67 protein leads to an effective elimination of proliferating tumor cells. Here we show a selective treatment for EGFR and Ki-67 positive cancer cells after light-controlled delivery of indocyanine green (ICG) photo-immunoconjugates. The Ki-67 antibody TuBB-9, which recognizes an active state of the protein, was labeled with different ratios of ICG and encapsulated into immuno-liposomes that selectively deliver the conjugates to EGFR overexpressing cells. To overcome endosomal entrapment of the delivered agents, ovarian carcinoma cells were treated with the photosensitizer benzoporphyrin monoacid derivative (BPD) and irradiated first for endosomal escape of the TuBB-9-ICG constructs. 24 h after irradiation TuBB-9-ICG antibodies showed a relocalization from spots in the cytoplasm to the cell nucleus. A second irradiation of the delivered TuBB-9-ICG led to a significant elimination of cells after Ki-67 inactivation.
Sijia Wang, Gereon Hüttmann, Tayyaba Hasan, and Ramtin Rahmanzadeh, "Molecular targeted PDT with selective delivery of ICG Photo-Immunoconjugates
(Conference Presentation)," Proc. SPIE 9694, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXV, 96940O (Presented at SPIE BiOS: February 14, 2016; Published: 26 April 2016); https://doi.org/10.1117/12.2217572.4848635766001.
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