ABSTRACT
Objective:To investigate the application of CD44 receptor-targeted nanoparticles HACDDP-DOX in the treatment of breast cancer, and to clarify its inhibitory effect on allograft breast cancer in the mice. Methods:Hyaluronic acid(HA)was used to construct a breast cancer targeted nanoparticle via green synthesis approach,and its particle size,stability and doxorubicin release profile at different pH conditions were measured. Then the breast cancer models were constructed by inoculating 4T1 cells into the mouse mammary fat pad.The model mice were randomly divided into control group,DOX/CDDP group and HACDDP-DOX group according to the tumor volumes and the body weights.PBS,free drug DOX/CDDP and HACDDP-DOX were intravenously injected into the allograft breast cancer models on the 1st,5th and 9th days after the tumor volume reached about 80 mm3. The antitumor effect and biosafety of HACDDP-DOX were evaluated by detecting the tumor volume,mouse weight and immunohistopathology.Moreover,the biological distribution of HACDDP-DOX in the mice was studied by biofluorescence imaging.Results:The average particle size of HACDDP-DOX was(80.0 ± 17.4)nm,which was stable under pH 7.4.Under acidic condition,the particle size was increased and the DOX was effectively released. Compared with DOX/CDDP group,the body weight of the mice in HACDDP-DOX group was increased(P<0.05) and the tumor volume was decreased(P<0.05).The HE staining results showed that the liver of the mice in control group had tumor metastasis and the alveolar septum was widened.The tumor tissue of the mice in DOX/CDDP group and HACDDP-DOX group were all necrotic,while in HACDDP-DOX group the degree of necrosis was significantly higher than DOX/CDDP group.Compared with DOX/CDDP group,the activity of Caspase-3 in HACDDP-DOX group was significantly increased(P<0.01),while the Ki-67 activity was significantly decreased (P<0.01).The biofluorescence imaging showed that the nanoparticle HACDDP-DOX could accumulate to the tumor site by targeting,and effectively release the drug.Conclusion:HACDDP-DOX nanoparticles can effectively target the breast cancer cells,reduce the toxicity of chemotherapy drugs,and enhance the therapeutic effect of breast cancer.
ABSTRACT
Objective:To observe the effect of distraction before discectomy (DBD) in the distraction of the height of anterior cervical space,and to explore its feasibility in restricting the over distraction.Methods:A total of 31 patients with cervical spondylotic myelopathy were treated with anterior cervical discectomy and fusion (ACDF).During surgery,the intervertebral space was distracted before discectomy,the procedure was defined as DBD technique.Before surgery,the distance from the arch top of inferior endplate of upper vertebrae of the index level to the midpoint of superior endplate of lower vertebrae was measured (H0).The same method was used to measure the adjacent proximal and distal intervertebral space heights (Hp and Hd),and the mean value of Hp and Hd,H,was regarded as a referential height that the index intervertebral space should be restored.During operation,the intervertebral space heights before (H1) and after (H2) discectomy with application of DBD were measured withthe aforementioned method.The pre-and post-operation index segment heights AB and A'B'were measured respectively.The change of index segment height was defined as △H (A'B'-AB),the index intervertebral space height after operation was defined as Hs (H0 +△H).The patients were divided into neck pain group and non-neck pain group according to their post-operative neck pain VAS scores.The radiographic data of the patients in two groups was analyzed and compared with statistical methods.Results:The post-operative neck pain incidence rate was 19.35％.During operation,after DBD,the intervertebral space height change △H1 was (1.19±0.51) mm.In non-neck pain group,the difference between H1 (6.95 mm±0.84 mm) and H (6.98 mm±0.70 mm) was not significant (P=0.80),and the difference between H2 (7.31 mm±0.90 mm) and H1 (6.95 mm± 0.84 mm) was significant (P＜0.01).In neck pain group,the difference between H2 (8.33 mm± 1.39 mm) and H1 (7.87 mm±1.35 mm) was significant (P＜0.01).In neck pain group,the △H was (3.04±0.42) mm;in non-neck pain group,the △H was (1.70±0.51) mm;the difference between two groups was significant (P＜0.01).In nonneck pain group,H1,H2 and H3 had good consistency with H.Conclusion:DBD can effectively control the distraction height of the index intervertebral space within 2 mm,also convenient to let the index intervertebral space be similar with the adjacent segment and easy to follow.