# Sonoporation, a Novel Frontier for Cancer Treatment: A Review of the Literature
## 3 Results
### Analysis of Results by Body District
#### 3.2.7 Ovaries  
In the study of [PERSON] et al. (2010) [25], a combination of ultrasound and innovative ultrasound-sensitive liposomes was employed to enhance interleukin-12 (IL-12) gene therapy for cancer, as in [26]. An impactful and noteworthy study by [PERSON] et al. (2014) [27] developed LHRH receptor-targeted and paclitaxel-loaded lipid microbubbles (TPLMBs) to enhance chemotherapy delivery in ovarian cancer treatment. In an ovarian cancer model, TPLMBs effectively bound to tumor cells, and ultrasound-mediated destruction of these microbubbles resulted in significantly improved therapeutic outcomes, including increased tumor apoptosis and reduced angiogenesis. The findings indicate that ultrasound-mediated intraperitoneal administration of targeted drug-loaded microbubbles holds promise for ovarian cancer treatment. Furthermore, it is worth noting that the stimulation in this case occurred at low frequencies, approximately 300 KHz. All the parameters obtained from the bibliography are reported in summary tables (Tables 1-8). One important parameter in US is the acoustic intensity, which, in this review, is expressed as ISPTA, as in most of the scientific literature on sonaporation. Compared to the application of diagnostic imaging, which applies ultrasound at intensities ranging from 0.05 to 0.5 W/cm\({}^{2}\), the application of ultrasound in surgery involves high intensities of 0.2-100 W/cm\({}^{2}\) and up to 10,000 W/cm\({}^{2}\). The use of therapeutic ultrasound ranges from high to low intensities. Thermal effects predominate in the former, and non-thermal effects, such as cavitation and transfer of drug, in the latter. Low-intensity US can be further subdivided into pulsed and continuous US, depending on the duty cycle. Pulsed US is characterized by ON/OFF cycles, while continuous US has a duty cycle of 100%. A new frontier to improve delivery to tumor cells could be the use of very low-intensity ultrasound (VLIUS), at intensities lower than 120 mW/cm\({}^{2}\)[13]. These would further reduce the generation of significant amounts of heat that would damage tissues and cells. By integrating the information from the elastic modulus and acoustic pressure tables, where both values were present, it was not possible to identify a correlation. However, this could be linked to the different study approaches and sample selection. Solid tumors present interesting characteristics that differentiate them from their surrounding environment. Palapation often serves as the initial diagnostic method, as tumors exhibit greater rigidity than their surroundings. At the cellular level, individual cancer cells appear to be softer and even more deformable than their healthy counterparts. Cancer cells undergo changes throughout the progression of the disease, acquiring biological properties not present in normal cells, such as the ability to replicate indefinitely [28]. One of the most remarkable phenomena associated with cancer is metastatic spreading. This leads to the formation of secondary tumors in distant organs, far away from the primary tumor site. The process involves cancer cells invading the bloodstream (intravasion) and then exiting the blood vessels to establish new tumors (extravasion). Research has revealed an essential aspect of tumor development: the role of stroma stiffening. Stiffening of the surrounding tissue induces tumor rigidity, which, in turn, contributes to tumor progression [29]. Understanding these unique characteristics of cancer cells and the mechanisms behind tumor progression is crucial in developing targeted and effective treatments to combat this disease. A further distinction between healthy and tumor cells is their stiffness, as reported in Table 8. Tumor cells, unlike their healthy counterparts, show a significantly lower elastic rigidity. This specific characteristic is closely linked to the ability of cancer cells to metastasize or spread throughout the body.