Intermittent F-actin Perturbations by Magnetic Fields Inhibit Breast Cancer Metastasis

F-actin(filamentous actin)has been shown to be sensitive to mechanical stimuli and play critical roles in cell attachment,migration,and cancer metastasis,but there are very limited ways to perturb F-actin dynamics with low cell toxicity.Magnetic field is a noninvasive and reversible physical tool that can easily penetrate cells and human bodies.Here,we show that 0.1/0.4-T 4.2-Hz moderate-intensity low-frequency rotating magnetic field-induced electric field could directly decrease F-actin formation in vitro and in vivo,which results in decreased breast cancer cell migration,invasion,and attachment.Moreover,lowfrequency rotating magnetic fields generated significantly different effects on F-actin in breast cancer vs.noncancerous cells,including F-actin number and their recovery after magnetic field retrieval.Using an intermittent treatment modality,low-frequency rotating magnetic fields could significantly reduce mouse breast cancer metastasis,prolong mouse survival by 31.5 to 46.0%(P<0.0001),and improve their overall physical condition.Therefore,our work demonstrates that low-frequency rotating magnetic fields not only can be used as a research tool to perturb F-actin but also can inhibit breast cancer metastasis through F-actin modulation while having minimum effects on normal cells,which reveals their potential to be developed as temporal-controlled,noninvasive,and high-penetration physical treatments for metastatic cancer.

Surface-modulated and thermoresponsive polyphosphoester nanoparticles for enhanced intracellular drug delivery

The chemical structure of end groups influenced the phase transition temperature of thermoresponsive polymers. We demonstrated a strategy for the preparation of the pH/thermo-responsive polymeric nanoparticles via subtle modification of end groups of thermoresponsive polymer segments with a carboxyl group and revealed its potential application for enhanced intracellular drug delivery. By developing a polymeric nanoparticle composed of poly(aliphatic ester) as the inner core and thermoresponsive polyphosphoester as the outer shell, we showed that end groups of thermoresponsive polyphosphoester segments modified by carboxyl groups exhibited a pH/thermo-responsive behavior due to the hydrophilic to hydrophobic transitions of the end groups in response to the pH. Moreover, by encapsulating doxorubicin into the hydrophobic core of such pH/thermo-responsive polymer nanoparticles, their intracellular delivery and cytotoxicity to wild-type and drug-resistant tumor cells were significantly enhanced through the phase-transition-dependent drug release that was triggered by endosomal/lysosomal pH. This novel strategy and the multi-responsive polymer nanoparticles achieved by the subtle chain-terminal modification of thermoresponsive polymers provide a smart platform for biomedical applications.