ネットワーク型共同研究拠点を支える 人・環境と物質をつなぐイノベーション創出ダイナミック・アライアンス 研究者データベース

Since discovering the enhanced permeability and retention effect, nanoparticle-based drug delivery systems (DDSs) have gained much attention as a chemotherapeutic agent. Due to a significantly increased vascular permeability in tumor tissue and an underdeveloped lymphatic system, nanoparticles (NPs) can passively target and accumulate in tumor tissue without causing drug side effects. Nanocarrier-containing drug molecules (e.g., liposomes, polymer micelles, and dendrimers) have been explored extensively over the past decades. However, these nanocarriers are considered one of the main hindrances to drug delivery applications, possibly causing long-term side effects and increasing systematic toxicity. To overcome this limitation, the concept of alternative carrier-free DDSs composed exclusively of hydrophobic drugs or prodrugs was developed.

Despite the impressive therapeutic efficiency of carrier-free DDSs, a lack of knowledge and methodologies concerning the intracellular fate, degradation, and conversion into the active drug of NPs after internalization drastically hinders further developments toward clinical applications. Knowing (i) if NPs enter the cells; (ii) if they are decomposed before entering the plasma membrane or efficiently degraded inside the cells and converted into active drugs; and (iii) if the cellular enzyme level plays a role in these processes, is fundamental for evaluating the suitability of this innovative carrier-free DDSs towards further steps. Herein, we designed carrier-free DDSs for the study based on fluorescence microscopy to unravel the dynamics of NPs inside cancer cells, including internalization, intracellular localization, particle degradation, and therapeutic efficiency.