Photochemical Internalization Using Natural Anticancer Drugs, Antimetabolites, and Nanoformulations: A Systematic...

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.