Ultrasound-mediated destruction of oxygen and paclitaxel loaded lipid microbubbles for combination therapy in hypoxic ovarian cancer cells

Abstract

We synthesized oxygen and paclitaxel (PTX) loaded lipid microbubbles (OPLMBs) for ultrasound mediated combination therapy in hypoxic ovarian cancer cells. Our experiments successfully demonstrated that ultrasound induced OPLMBs destruction significantly enhanced the local oxygen release. We also demonstrated that OPLMBs in combination with ultrasound (300 kHz, 0.5 W/cm(2), 15s) yielded anti-proliferative activities of 52.8 ± 2.75% and cell apoptosis ratio of 35.25 ± 0.17% in hypoxic cells at 24h after the treatment, superior to other treatment groups such as PTX only and PTX-loaded MBs (PLMBs) with or without ultrasound mediation. RT-PCR and Western blot tests further confirmed the reduced expression of HIF-1α and MDR-1/P-gp after ultrasound mediation of OPLMBs. Our experiment suggests that ultrasound mediation of oxygen and drug-loaded MBs may be a useful method to overcome chemoresistance in the hypoxic ovarian cancer cells.

Ultrasound mediated delivery of oxygen and LLL12 loaded stimuli responsive microdroplets for the treatment of hypoxic cancer cells

“…For both OLMs and LMs, the CFF process achieves LLL12 EE levels of above 94%, much higher than that of a conventional emulsification process. After applying therapeutic ultrasound pulses of 1 MHz at an intensity of 3 W/cm 2 and a duty cycle of 20% for the duration of 2 min, both OLMs and LMs release over 80% of the loaded drugs within less than 1 h. Simultaneously, oxygen is also released from the OLMs for reversed chemoresistance and enhanced anticancer potency, as suggested in previous works242526.…”

Calcitriol and Calcidiol Can Sensitize Melanoma Cells to Low–LET Proton Beam Irradiation

“…However, inhibition of proliferation by calcidiol, with no effect in the case of calcitriol in both BHM Ma and BHM Ab cells requires further explanation. It has been proposed that one of the factors influencing the responsiveness of melanoma cell lines to vitamin D 3 is melanin pigmentation [53,54], which would explain the decrease in VDR expression with concomitant decrease in anti-proliferative response to 1,25(OH) 2 D 3 in human melanoma. It is possible that a similar mechanism could underlie the resistance of BHM Ma, which produces melanin pigment also when cultured in a medium with low tyrosine content [55].…”

Co‐delivery of hypoxia inducible factor‐1α small interfering RNA and 5‐fluorouracil to overcome drug resistance in gastric cancer SGC‐7901 cells

“…The tumor hypoxia microenvironment enhances the resistance of tumor cells through many mechanisms. 41 First, tumor hypoxia can result in the cellular uptake of chemotherapy drugs being reduced. 42 Second, the number of migration tumor cells is increased under conditions of hypoxia.…”

“…41 First, tumor hypoxia can result in the cellular uptake of chemotherapy drugs being reduced. 41 First, tumor hypoxia can result in the cellular uptake of chemotherapy drugs being reduced.…”