光化学内化（PCI）是一种新颖的微创药物输送技术，可促进治疗分子输送到细胞的细胞质中。本研究利用PCI技术旨在增强现有的抗癌药物及新型纳米制剂针对乳腺癌和胰腺癌细胞的治疗指数。前线抗癌药物作为基准PCI控制药物，用博来霉素进行测试；具体而言，测试了三个长春花生物碱（长春新碱、长春碱、长春云南白药），两个紫杉烷类（多西他赛和紫杉醇），两种抗代谢物（吉西他滨和卡培他滨），紫杉烷类与抗代谢物的联合用药，以及两种纳米级制剂（鲨烷衍生物和聚合物结合的吉西他滨衍生物）在三维PCI in vitro模型中进行了测试。惊人的是，我们发现，一些药物分子与其对照组（未使用PCI技术或直接与博来霉素对照）相比表现出了显着提高的治疗效果。几乎所有药物分子都表现出了治疗效率的提高，但更有趣的是，我们追踪到了几种药物分子，它们的IC70指数得到了多倍的提高（范围在5000倍到170,000倍）。有趣的是，PCI输送长春花生物碱（尤其是PCI-长春新碱）和部分测试的纳米制剂在效力、效果和协同作用等治疗结果方面表现出了令人印象深刻的优异表现，这是通过细胞存活率试验来确定的。该研究构成了未来基于PCI的精准肿瘤治疗疗法的系统指南。

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.