We developed the first visible light activatable Pt (IV) pro-drug that uses CD36, a transmembrane protein for a higher drug uptake in cisplatin resistance ovarian cancer. CD36 dependent cell entry facilitates the higher accumulation of pro-drug into the cell and the photoactivation allows immediate release of the active drug towards elimination of ovarian cancer cells. In this study we modified lipophilic fatty acid-like Pt(IV) compound with a fluorescein moiety for a light controllable activation. This modification allows the compound to have lower dark toxicity and readily releases active Pt compound upon irradiation by 490 nm blue LED. GFAAS (Graphite Furnace atomic absorption spectroscopy) experiments confirm the higher cellular uptake of the Pt(IV) compound in cisplatin resistant ovarian cancer in a CD36 dependent manner. Photoactivation was explained with computational studies and release of the active Pt compound was confirmed by the increase of fluorescence signal of free dye molecule that escaped after irradiation. Flow cytometry data reveal the nuclear damage caused by the compound after the light irradiation and cell death via apoptosis. As a summary, we have demonstrated a new chemical design of visible light-activatable Pt (IV) prodrugs that exploit the upregulated CD36 to facilitate cell entry in ovarian cancer. This work is a proof-of-concept study toward engineering tumor-specific photoactivatable metallodrugs.

<b>Figure 1:</b> Graphical representation of mechanism of action of the visible light-activatable Pt(IV) prodrug (1)

Figure 1: Graphical representation of mechanism of action of the visible light-activatable Pt(IV) prodrug (1)

<b>Figure 2: </b>Fluorescence images of the live (green)/dead (red) assays of the A2780cis cells treated with 1 ([Pt] = 20 μM, 6 h) recorded without (left) or with (right) 490-nm irradiation (2.36 mW/cm2, 20 min). Scale bar is 20 µm

Figure 2: Fluorescence images of the live (green)/dead (red) assays of the A2780cis cells treated with 1 ([Pt] = 20 μM, 6 h) recorded without (left) or with (right) 490-nm irradiation (2.36 mW/cm2, 20 min). Scale bar is 20 µm

Srijana Bhandari

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