Rigidity of Polymer Micelles Affects Interactions with Tumor Cells

One of the main challenges in cancer therapy is the capability of drug penetration to the core of the tumor mass in order to achieve substantial efficacy. Di-block polymer micelles are used as a drug delivery system with markedly benefits including small dimension, ease of preparation, controlled drug release, drug targeting and reduction of side effects. However polymer micelles are generally limited by the degradation time dictated by the polymers in use, making it usable for short term after preparations. Moreover the ability of polymer micelles to penetrate tissues is relatively low. We addressed that issue and developed a novel form of lyophilized micelles i.e Solidified Polymer Micelle (SPM). The SPMs can be loaded with a variety of small molecule drugs and importantly can endocytose rapidly into cancer cells. Interestingly we found that the SPMs also exocytose from the cells and penetrate into multi-layer cellular cultures (spheroids). The combination of endocytosis and exocytosis, termed transcytosis, can provide a mechanism for drug carrier penetration into tumors, in addition to extra-cellular transport. By that, we hypothesize that SPM can reach deeper to the inner parts of the tumor, enhancing the exposure of the core to the chemotherapy. We present here detailed measurements of the SPM including examinations of particle size, stability, drug release kinetics and cell transcytosis. We conclude that SPM can potentially be used as an improved drug vehicle with elevated tumor penetration ability and that further studying of SPM is a promising field.