| BackgroundHigh intensity focused ultrasound(HIFU) is a rising minimally invasive or non-invasive tumor treatment in 21 st century, currently in the clinical application of HIFU in the treatment of tumors including prostate cancer,liver cancer, renal cell carcinoma, pancreatic cancer, bladder cancer, uterine fibroids, shallow soft tissue tumor etc.. But the efficiency of HIFU ablation of tumors is low, the focal region(FR) formed by HIFU ablation is just several millimeters, it would spend a lot of time and energy to complete the "removal" of a large tumor. In addition, the ultrasonic energy decreases exponentially with the distance increases in the process of tissue propagation, so with the increase of tumor depth that the HIFU energy also need to increase greatly. The attenuation characteristics of ultrasonic and HIFU restriction in the treatment, resulting the dilemma of lengthy treatment time, low therapeutic efficacy, increased medical costs, caused skin burns and adjacent organ damage or adverse reactions. On the otherhand, the monitoring technology of HIFU Therapeutic System mainly is ultrasound and MRI, because of ultrasound imaging faster than MRI that can be displayed different range and moved flexibly, the real-time monitoring equipment of clinical HIFU Therapeutic system mostly is ultrasonic. But the quality of ultrasound images were differential and artifacts significantly, that interfered with the diagnosis and treatment.These problems make the security and efficiency of HIFU affected and restricting its development. Therefore, to explore new method to enhance the HIFU therapy efficiency is very necessary.Research objectives1. To investigate the feasibility of HIFU ablating liver tissue in rabbits by the "hat-type" method, to improve the efficiency and safety on benign and malignant solid tumors.2. To prepare the hematoporphyrin monomethyl ether(HMME) coated polymer nanoparticles as a multifunction contrast agent(MBPLGA-HMME),detect their physical properties and the drug properties changed situation.To investigate the feasibility of imaging and treatment of one of the sets.Research methods1. Totally 60 healthy rabbits were divided into group A and group B,30 rabbits in each group. The two groups were divided into A1, A2, A3 subgroups and B1, B2, B3 subgroups, each subgroup was 10 rabbits. Group A was irradiated the liver tissue of rabbits with different power(A1:200 W,A3:300 W, A2:250 W), group B only changed the angle between two irradiation surface(B1:55°, B2:90°, B3:125°). Total irradiation time and ultrasonic energy were calculated, the size and shape of the coagulation necrosis were observed and calculated.2. MBPLGA-HMME was prepared by multi-emulsion method, the mean size and structure, the morphology and the concentration of HMME loaded in PLGA microcapsules were assessed by several analytical methods,compared the changes of HMME and MBPLGA-HMME microspheres using ultrasound/photoacoustic imaging in vitro and going photoacoustic imaging preliminarily in vivo.Research results1. Rabbit livers in A1 subgroup failed to form a linear continuous or uniform necrosis, in A2 and A3 subgroup formed a continuous linear necrosis, and composed of uniform rules of ellipsoid shaped necrosis, but the A3 subgroup of energy is too large that causing the surrounding viscera appeared serious complications, so we choose the parameter of A2 subgroup to continue explore the influence of angle to the coagulation necrosis of body; The volume of coagulative necrosis in B1, B2, B3 subgroups were(3907.85 ± 565.53) mm3,(4431.49 ± 721.36) mm3,(3729.46±1049.29)mm3, respectively; Ratios of long axis in the near sound and short axis of the near sound in B1, B2, B3 subgroups were 2.14± 0.25, 1.47 ± 0.26, 1.06 ± 0.12, respectively. It was showed that keep consistent with the ablation parameters, with two surface angle increasing,the ratio of long axis in the near sound and short axis of the near sound was decreased gradually(P < 0.005), but the volume of coagulation necrosis was not significantly increased with the increase of the two surface angles.2. Successfully prepared MBPLGA-HMME nanospheres, they were red powder, which became pale red suspension after dissolved in double distilled water, the microspheres with spherical shape and uniform size, no aggregation and adhesion phenomenon under light microscope(LM), laser confocal scanning microscopy(LCSM) images showed HMME evenly distributed in the microspheres and emitted red fluorescence, light microscopy(LM) and transmission electron microscopy(TEM) showed that MBPLGA-HMME nanoparticles were a core-shell structure with an obvious black shell that HHME was mainly distributed in the shell. The mean size of MBPLGA-HMME was 497.26±68.25 nm measured by a Laser Particle Size Analyzer System. UV spectrophotometer detected MBPLGA-HMME and HMME solution absorption spectra were 401 nm that didn’t appear shift phenomenon. Photoacoustic imaging in vitro showed that the concentration of MBPLGA-HMME is 408μmol/L, 816μmol/L, 1632μmol/L, that its average photoacoustce signal intensity of were 0.2009+0.0636, 0.3789+0.0431,0.5380+0.0997, respectively; the same average concentration of photoacoustic signal HMME solution gradient values were 0.0738 + 0.0133,0.1137 + 0.0065, 0.217 + 0.0270, the comparison results between and within group were different, but the basic properties of the drug does not changed. MBPLGA-HMME in nude mice by intravenous injection, can be carried out photoacoustic imaging in vivo. MBPLGA-HMME can accumulate at the tumor site after giving the tumor bearing mice an intravenous injection and do photoacoustic imaging via excited by the laser.Research conclusions1. The method of "hat-type" can effectively superimposed focal extraterritorial near-field acoustic energy and spend less energy and time to form larger coagulation necrosis, it can shorten the duration of irradiation,reduce the excessive release of energy and the occurrence of adverse reactions.2. Successfully prepared PLGA microspheres loaded with HMME drugs, the water-soluble of HMME was improved and the light absorption properties was maintained that can use to ultrasound/ photoacoustic imaging, provides the basis for subsequent imaging and therapy in vitro and in vivo. |
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