The absence of lymphatic vessels in
tumors leads to the retention of interstitial fluid, and the formation of an inverse pressure difference between the
tumor and blood vessels hinders drug delivery deep into the
tumor, which leads to
tumor recurrence and
metastasis. Therefore, we designed a novel strategy to downregulate
tumor interstitial fluid pressure (TIFP) by water splitting in the
tumor interstitium based on piezoelectric catalysis nanomedicine. First, the chemotherapeutic drug
doxorubicin (DOX) was loaded on the piezoelectric catalytic material MoS2 and then encapsulated with
tumor cell membrane (CM) to obtain MD@C. MD@C could not only target the
tumor through homologous targeting but, more importantly, also triggered piezoelectric catalytic water splitting under ultrasound (US) stimulation; as a result, the TIFPs of U14 and PAN02
tumor-bearing mice were reduced to 57.14% and 45.5%, respectively, and the
tumor inhibition rates of MD@C were 96.75% and 99.21%, which increased the perfusion of blood-derived drugs in the
tumors. Moreover, the
hydroxyl radicals generated by piezoelectric catalysis could effectively inhibit the growth of
tumors in combination with DOX. Consequently, the piezoelectric catalytic water splitting strategy of MD@C can enhance drug delivery, providing a new universal platform for the treatment of solid malignant
tumors.