Photochemical internalization (PCI) is a novel, minimally invasive
drug delivery technology that facilitates the delivery of therapeutic molecules into the cytosol of cells. In this work, PCI was utilized in an effort to enhance the therapeutic index of the existing anticancer drugs as well as novel nanοformulations against breast and
pancreatic cancer cells. Frontline anticancer drugs were tested with
bleomycin as a benchmark PCI control; namely, three
vinca alkaloids (
vincristine,
vinorelbine, and
vinblastine), two
taxanes (
docetaxel and
paclitaxel), two
antimetabolites (
gemcitabine and
capecitabine), a combination of
taxanes with
antimetabolites, and two nano-sized formulations (
squalene- and
polymer-bound
gemcitabine derivatives) were tested in a 3D PCI in vitro model. Strikingly, we discovered that several
drug molecules exhibited remarkably augmented therapeutic activity by several orders of magnitude compared to their respective controls (without PCI technology or directly compared with
bleomycin controls). Nearly all
drug molecules showed enhanced therapeutic efficiency, but more interestingly, we traced several
drug molecules that showed multi-fold enhancement (ranging from 5000- up to 170,000-fold enhancement) in their IC70 indices. Interestingly, PCI delivery of the
vinca alkaloids (especially PCI-
vincristine), and some of the nanoformulations tested, was seen to perform impressively across all of the treatment outcomes of potency, efficacy, and synergy─as determined by means of a cell viability assay. The study constitutes a systematic guide for the development of future PCI-based therapeutic modalities for precision oncology.