Fizikalni mehanizmi i metode u tumorskim terapijama i prijenosu lijekova do tumora

In addition to several well-known drug delivery strategies developed to facilitate effective chemotherapy with anticancer agents, some new approaches have been recently established, based on specific effects arising from the applications of ultrasound, magnetic and electric fields on drug delivery systems. This paper gives an overview of newly developed methods of drug delivery to tumors and of the related anticancer therapies based on the combined use of different physical methods and specific drug carriers. The conventional strategies and new approaches have been put into perspective to revisit the existing and to propose new directions to overcome the threatening problem of cancer diseases.Osim dobro poznatih metoda prijenosa lijekova u kemoterapijskom pristupu liječenja tumora, nedavno su otkriveni novi načini prijenosa koji se zasnivaju na specifičnim mehanizmima uzrokovanim upotrebom ultrazvuka, magnetskih i električnih polja. Članak sadrži prikaz fizikalnih mehanizama na kojima se temelje ove nove metode, kao i pregled novootkrivenih prijenosnika lijekova (Pluronske micele, magnetoliposomi, magnetski fluidi), novih terapija tumora (magnetska hipertermija, elektrokemoterapija) i najnovijih istraživanja temeljenih na fizikalnom pristupu ovoj problematici

Ultrasound attenuation estimation using backscattered echoes from multiple sources

The objective of this study was to devise an algorithm that can accurately estimate the attenuation along the propagation path (i.e., the total attenuation) from backscattered echoes. It was shown that the downshift in the center frequency of the backscattered ultrasound echoes compared to echoes obtained in a water bath was calculated to have the form Δf=mfo+b after normalizing with respect to the source bandwidth where m depends on the correlation length, b depends on the total attenuation, and fo is the center frequency of the source as measured from a reference echo. Therefore, the total attenuation can be determined independent of the scatterer correlation length by measuring the downshift in center frequency from multiple sources (i.e., different fo) and fitting a line to the measured shifts versus fo. The intercept of the line gives the total attenuation along the propagation path. The calculations were verified using computer simulations of five spherically focused sources with 50% bandwidths and center frequencies of 6, 8, 10, 12, and 14 MHz. The simulated tissue had Gaussian scattering structures with effective radii of 25 μm placed at a density of 250∕mm3. The attenuation of the tissue was varied from 0.1 to 0.9 dB∕cm-MHz. The error in the attenuation along the propagation path ranged from −3.5±14.7% for a tissue attenuation of 0.1 dB∕cm-MHz to −7.0±3.1% for a tissue attenuation of 0.9 dB∕cm-MHz demonstrating that the attenuation along the propagation path could be accurately determined using backscattered echoes from multiple sources using the derived algorithm

Enhanced tumor cell killing by ultrasound after microtubule depolymerization

Recent studies show that tumor cells are vulnerable to mechanical stresses and undergo calcium‐dependent apoptosis (mechanoptosis) with mechanical perturbation by low‐frequency ultrasound alone. To determine if tumor cells are particularly sensitive to mechanical stress in certain phases of the cell cycle, inhibitors of the cell‐cycle phases are tested for effects on mechanoptosis. Most inhibitors show no significant effect, but inhibitors of mitosis that cause microtubule depolymerization increase the mechanoptosis. Surprisingly, ultrasound treatment also disrupts microtubules independent of inhibitors in tumor cells but not in normal cells. Ultrasound causes calcium entry through mechanosensitive Piezo1 channels that disrupts microtubules via calpain protease activation. Myosin IIA contractility is required for ultrasound‐mediated mechanoptosis and microtubule disruption enhances myosin IIA contractility through activation of GEF‐H1 and RhoA pathway. Further, ultrasound promotes contractility‐dependent Piezo1 expression and localization to the peripheral adhesions where activated Piezo1 allows calcium entry to continue feedback loop. Thus, the synergistic action of ultrasound and nanomolar concentrations of microtubule depolymerizing agents can enhance tumor therapies