Low intensity focused ultrasound responsive microcapsules for non-ablative ultrafast intracellular release of small molecules

Abstract

Focused ultrasound (FU) is in demand for clinical cancer therapy, but the possible thermal injury to the normal peripheral tissues limits the usage of the ablative FU for tumors with a large size; therefore research efforts have been made to minimize the possible side effects induced by the FU treatment. Non-ablative focused ultrasound assisted chemotherapy could open a new avenue for the development of cancer therapy technology. Here, low intensity focused ultrasound (LIFU) for controlled quick intracellular release of small molecules (M_w ≤ 1000 Da) without acute cell damage is demonstrated. The release is achieved by a composite poly(allylamine hydrochloride) (PAH)/poly-(sodium 4-styrenesulfonate) (PSS)/SiO₂ microcapsules which are highly sensitive to LIFU and can be effectively broken by weak cavitation effects. Most PAH/PSS/SiO₂ capsules in B50 rat neuronal cells can be ruptured and release rhodamine B (Rh-B) into the cytosol within only 30 s of 0.75 W cm⁻² LIFU treatment, as demonstrated by the CLSM results. While the same LIFU treatment shows no obvious damage to cells, as proved by the live/dead experiment, showing that 90% of cells remain alive.