Challenges in the use of nanostructures as carriers of nucleic acids in clinical practice

ABSTRACT The delivery of nucleic acids to cells is considered a crucial step for the success of genetic modifications aimed at therapeutic purposes or production of genetically modified animals. In this context, nanotechnology is one of the most promising fields of science, with the potential to solve several existing problems. Nanostructures have desirable characteristics to be used as carriers, such as nanometric size, large surface area, cell internalization capacity, prolonged and controlled release, among others. Genetically modified animals can contribute to the production of biopharmaceuticals, through the expression of high-associated-value molecules. The production of these animals, also known as biofactories, further enhances Brazilian agribusiness, since it allows adding value to the final product, and favors the integration between the agricultural market and the pharmaceutical sector. However, there is a growing concern about the safety and possible harmful effects of nanostructures, since data on the safe use of these materials are still insufficient. The objective of this review was to address aspects of the use of nanostructures, mainly carbon nanotubes as nucleic acid carriers, aiming at the production of genetically modified animals, with the certainty that progress in this field of knowledge depends on more information on the mechanisms of interaction between nanostructures, cells and embryos, as well as on its toxicity.

Application progress of carbon nanotube-based targeted ultrasound contrast agent in tumors / 中国介入影像与治疗学

Nano-targeted ultrasound contrast agents have many advantages, such as no radiation, small side effects, real-time imaging and high targeting, etc. Among them carbon nanotube (CNT) has unique optical, electrical and acoustic properties, as well as high specific surface area and good biocompatibility. By embellishing or modifying CNT, excellent properties can be prepared and used in diagnosis and treatment of tumors. The application progress of CNT-based targeted ultrasound contrast agents in tumors were reviewed in this article.

Clinical significance of carbon nanoparticles in breast cancer lymphadenectomy / 中国基层医药

Objective To evaluate the clinical application value of active carbon nanoparticles to guide breast cancer tiny lymphadenectomy.Methods 50 patients with breast cancer were enrolled in the study and were divided into two groups by random number table.Active carbon particle was injected locally to guide the regional lymph nodes dissection in 25 cases as study group,and the traditional method was performed in 25 cases as observation group.Numbers of dissected lymph nodes were compared between two groups.Results The average number of eliminated small lymph nodes in the study group was dramatically more than that in the observation group[(23.60 ±4.61)vs. (14.60 ±5.16),t =3.47,P <0.05].There was significant difference between the study group and the observation group in the small ambulant lymph nodes[(5.80 ±1.49)vs.(2.89 ±1.66),t =2.91,P <0.05)].Conclusion Active carbon injected locally can eliminate not only more small lymph nodes,but also more small ambulant lymph nodes.

Flexible sensors and their application in healthcare / 军事医学

The traditional approach to accessing healthcare information restricts the further development of healthcare services,thus unable to meet the growing needs of individual healthcare.The flexible sensor technology has emerged along with the development of new materials,machinery and manufacturing technology.As a result,textiles,accessories,human skin and even internal body organs can be integrated with various sensors.The popularization of flexible sensors provides new methods for monitoring health,improving therapeutics,investigating disease status and building the human-machine in-terface.Through a systematic investigation of literature,this paper reviews the applications of flexible sensors in health-care,discusses the key technologies,and introduces the common materials and manufacturing technology.

Preparation and performance of LID-MWCNT based sustained release targeted drug delivery system / 天津医药

Objective To prepare a targeted antitumor drug delivery system using large-inner-diameter multi-walled carbon nanotubes (LID-MWCNTs) for sustained release and to study its performance. Methods LID-MWCNTs were puri?fied and oxidized,then use nanocarriers and USTs as homologous blockers. Folic acid and fluorescent labels were conjugat?ed onto the external surfaces of nanocarriers. CDDP (cisplatin) was encapsulated and ultrashort tubes (USTs) were employed to block the drug entry/exit paths. The microstructure of resulted drug delivery system (DDS) was observed, while drug load?ing efficiency and drug release profile in vitro were determined. The tumor-targeting property and cytotoxicity of DDS were also assessed. Results LID-MWCNT based sustained release targeted drug delivery system was established. Drug loading efficiency of CDDP@UST-FA-LID-MWCNTs was as high as 70.97%. A typical biphasic sustained release pattern was dem?onstrated, and the accumulating release time was 18 h. DDS exhibited a certain kind of tumor-targeting property, and inhibit?ed proliferation of tumor cells in a dose-dependent manner. Conclusion CDDP@UST-FA-LID-MWCNT drug delivery system exhibited an improved drug loading efficiency and a sustained drug release profile. It could specifically target the tu?mor cells and had a significant antitumor effect.

Accumulation of intravenously injected carboxylated single-walled carbon nanotubes in rat axillary lymph nodes / 中国组织工程研究

BACKGROUND:Lymph-targeted tracing and therapy based on carbon nanotubes have been one of the hottest researches on targeting tumor diagnosis and treatment. To evaluate the accumulation of carbon nanotubes in axil ary lymph node can provide experimental evidences for developing nano-tracers and drug carriers which are more lymph-specific and more biocompatible. OBJECTIVE:To study the accumulation of the intravenously injected carboxylated single-wal ed carbon nanotubes in axil ary lymph nodes of Sprague-Dawley rats, and to evaluate their effect on blood cel s. METHODS:Sixty-four Sprague-Dawley rats were randomly divided into two groups. Rats in testing group were injected with carboxylated single-wal ed carbon nanotubes suspension (2 mg/kg), while those in control group were injected with 5%glucose solution (1 mL/kg), both through the tail vein, three times per week. Four periods of 7, 60, 90 and 120 days were set (the 120-day period referred to 90 days of administration fol owed by 30 days of drug withdrawal). At the end of each period, eight rats from each group were randomly picked out, to col ect blood samples via the abdominal aorta for blood routine test. Final y the axil ary lymph nodes were observed, and the lymph node samples of rats in the testing group were col ected and analyzed at 120 days by transmission electron microscope. RESULTS AND CONCLUSION:Compared with the control group, black staining of axil ary lymph nodes of rats in testing group was not obvious at the end of the 7-day period. However, with the increase of the dosing periods, the lymph nodes of the rats in the testing group became enlarged, firm and black stained, coupled with a significant rising in the percentage of blood neutrophils. After 30 days of drug withdrawal, the size of the rat axil ary lymph nodes was reduced and black staining partly faded, with the decreasing of blood neutrophil percentage. Under the transmission electron microscope, abundant carboxylated single-wal ed carbon nanotubes were uptaken by lymphocytes to form a large number of phagocytic vacuoles after drug withdrawal for 30 days. It indicates that the short-term tracing of rat axil ary lymph nodes by carboxylated single-wal ed carbon nanotubes injected through the tail vein is relatively weak, while the long-term intravenous injection can cause their accumulation in rat axil ary lymph nodes, coupled with the increase of neutrophils;after drug withdrawal, the carboxylated single-wal ed carbon nanotubes can be slowly cleared by the lymph nodes.

Studies on the lymphatic tropism and lymph cells apoptosis of cisplatin-nano carbon suspension in the rats / 中华妇产科杂志

Objective To research the lymphatic tropism and lymph cell apoptosis of cisplatin-nano carbon suspension in rats with the aim of proposing a new way for chemotherapy.Methods A total of 72 Wistar rats were randomly divided into two groups.For the experimental group,cisplatin-nano carbon suspension 0.3 ml (4 mg/ml) was injected subcutaneously into Wistar rats' plantar.For the control group,cisplatin 0.3 ml (4 mg/ml) was injected intravenously.Cisplatin concentration in the inguinal lymphatic tissue and plasma was determined by high performance liquid chromatography (HPLC) at 1,2,3,4,5 and 6 hours after drug administration.The apoptosis of lymph cell was detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay (TUNEL).Targeting ability were evaluated and compared by targeting index (TI),selecting index (SI) and relative extraction efficiency (RE).SPSS 17.0 statistical software was used to analyze the differentiation of the cisplatin concentration and apoptosis index (AI) among various groups.DAS software was used to evaluate the lymphatic tropism.Results The cisplatin concentration of lymphatic tissue in experimental group were respectively (1.03±0.32),(3.00±0.91),(2.20±0.73),(1.56±0.38),(1.30±0.74) and (0.78±0.34) μg/g after administration 1,2,3,4,5 and 6 hours,while in control group were (0.49±0.21),(1.02±0.70),(0.59±0.50),(0.56±0.21),(0.47±O.18) and (0.36±0.13) μg/g,in which there were significant difference at every times (all P＜0.05) except at 1 hour (P=0.173).The cisplatin concentration in plasma were significant higher in the experimental group than those in the control group at various times (all P＜0.05),the former were respectively (0.57±0.28),(1.22±0.45),(0.61 ±0.18),(0.51 ±0.13),(0.45 ±0.13) and (0.40±0.07) μg/ml,while the latter were respectively (3.12± 0.33),(4.09± 0.48),(2.56 ± 0.38),(2.05 ± 0.13),(1.81 ± 0.28) and (1.44± 0.40) μg/ml.Values of TI were respectively 2.12,2.93,3.73,2.78,2.76 and 2.19 and SI were 1.80,2.45,3.63,3.07,2.86 and 1.93.Value of RE was 2.86.The AI in experimental group were respectively (16.5±5.2)％,(30.2±2.8)％,(51.7±4.3)％,(69.8±3.2)％,(80.1 ±4.3)％ and (89.7±8.5)％,while in control group were respectively(1.3±0.8)％,(2.4±1.7)％,(3.2±1.1)％,(3.9±2.6)％,(5.1±2.1)％ and (6.3±2.3)％,in which there were significant difference at every points (all P＜0.05).Conclusions The nano carbon has the character of lymphatic tropism,and could send cisplatin to lymphatic tissue to achieve a higher concentration.The trait may break a new way for chemotherapy targeting lymph metastasis.

Application of functionalized carbon nanotube in tumor targeted therapy / 国际肿瘤学杂志

Targeted therapy means transporting drugs to certain tissue,aiming at increasing the utilization of drugs as well as reducing cytotoxicity.Chemotherapy drugs carried by carbon nanotube have high pharmaceutical activity and tumor control rate,compared with drugs alone.Carbon nanotube combined with immunotherapy drugs and nucleic acid can treat tumors at immunology and gene level.

Application prospect of carbon nanotubes for the treatment of cerebral ischemia with mesenchymal stem cells / 国际脑血管病杂志

Mesenchymal stem cells (MSCs) play a neuroproteetive effect via a variety of mechanisms.They provide a new idea for the treatment of cerebral ischemia.However,the inadequate sources have significantly limited the possible clinical applications.Carbon nanotubes (CNTs),a new nanomaterials,can not only promote the adhesion,proliferation and differentiation of MSCs in vitro,but also as the cell carriers they can provide good microenvironmental guarantee for the survival of MSCs through the regulation of secretion of cytokines and neurotrophic factors,as well as regulation of biological characteristics of neurons,glial cells,and macrophages after their cell transplantation,provide a good microenvironment guarantee for the survival of MSCs,and promote the effect of MSCs on the therapeutic effect of cerebral ischemia.

Multiwalled carbon nanotubes improve the morphology of the femoral head of a rabbit model of steroid-induced necrosis of femoral head / 中国组织工程研究

BACKGROUND: Multiwaled carbon nanotubes can accelerate the proliferation and differentiation of osteoblasts, and exert a therapeutic effect on steroid-induced necrosis of femoral head (SNFH). OBJECTIVE:To investigate the function of multiwaled carbon nanotubes in the establishment of a rabbit model of SNFH. METHODS:Thirty-six New Zealand white rabbits were divided randomly into three groups. In treatment group, 16 rabbits were given intraglutealy injection of dexamethasone (2.5 mg/kg) every day and injection of 1 mL liquor of multiwaled carbon nanotubes (0.1 g/L) into the bilateral femur medulary space every week. In model group, 16 rabbits were given intraglutealy injection of dexamethasone (2.5 mg/kg) every day and injection of 1 mL normal saline into the bilateral femur medulary space every week. In control group, four rabbits were given intraglutealy injection of 2 mL normal saline every day and injection of 1 mL normal saline into the bilateral femur medulary space every week. RESULTS AND CONCLUSION: Four weeks after hormone injection, the trabeculae began to exhibit a smal amount of thinner fractures, an accumulation of fatty tissue in the bone marrow were obvious, bone marrow fat cels became bigger and microvascular thrombosis appeared in the model group, while there was no positive histopathological manifestation in the treatment group. This indicates that the multiwaled carbon nanotubes can extenuate pathological damage to the femoral head to a certain extent.