Design, strategies, and therapeutics in nanoparticle-based siRNA delivery systems for breast cancer.

Utilizing small interfering RNA (siRNA) as a treatment for cancer, a disease largely driven by genetic aberrations, shows great promise. However, implementing siRNA therapy in clinical practice is challenging due to its limited bioavailability following systemic administration. An attractive approach to address this issue is the use of a nanoparticle (NP) delivery platform, which protects siRNA and delivers it to the cytoplasm of target cells. We provide an overview of design considerations for using lipid-based NPs, polymer-based NPs, and inorganic NPs to improve the efficacy and safety of siRNA delivery. We focus on the chemical structure modification of carriers and NP formulation optimization, NP surface modifications to target breast cancer cells, and the linking strategy and intracellular release of siRNA. As a practical example, recent advances in the development of siRNA therapeutics for treating breast cancer are discussed, with a focus on inhibiting cancer growth, overcoming drug resistance, inhibiting metastasis, and enhancing immunotherapy.

Diagnostic approach to thyroid cancer based on amino acid metabolomics in saliva by ultra-performance liquid chromatography with high resolution mass spectrometry.

Thyroid cancer is a malignant disease with dramatically low advanced-stage 10-year survival. Meanwhile, the metabolites in saliva are becoming a wealthy source of disease biomarkers. However, there is a lack of non-invasive analytical methods for the identification of biomarkers in saliva for the preoperative diagnosis of thyroid cancer. Therefore, we developed an ultra-high performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) method to simultaneously determine the metabolic levels of 10 amino acids in saliva, aiming to study the amino acid metabolism profile to promote early diagnosis of thyroid cancer. We tested unstimulated whole saliva from patients with papillary thyroid carcinoma (PTC; n = 61) and healthy controls (HC; n = 61), and used receiver operating characteristic (ROC) curves to establish the diagnostic value of potential markers. The method validation results showed good precision, linearity (R2 > 0.99), recovery (92.2 %-110.3 %), intra- and inter-day precision (RSD < 7 % and RSD < 9 %, respectively). The concentration of 10 amino acids was significantly different between PTC and HC in human salivary analysis (P < 0.05), the area under the curve (AUC) values of a single marker for the diagnosis of PTC were ranging from 0.678 to 0.833. A panel of alanine, valine, proline, phenylalanine was selected in combination yielded the AUC of 0.936, which will improve the accuracy of early diagnosis of thyroid cancer (sensitivity: 91.2 %; specificity: 85.2 %). This study proved the possibility of salivary amino acid biomarkers for PTC early diagnosis, providing a simple auxiliary way for the non-invasive diagnosis of thyroid cancer.

In-situ re-melting and re-solidification treatment of selective laser sintered polycaprolactone lattice scaffolds for improved filament quality and mechanical properties.

Selective laser sintering (SLS) is a promising additive manufacturing technique that produces biodegradable tissue-engineered scaffolds with highly porous architectures without additional supporting. However, SLS process inherently results in partially melted microstructures which significantly impair the mechanical properties of the resultant scaffolds for potential applications in tissue engineering and regenerative medicine. Here, a novel post-treatment strategy was developed to endow the SLS-fabricated polycaprolactone (PCL) scaffolds with dense morphology and enhanced mechanical properties by embedding them in dense NaCl microparticles for in-situ re-melting and re-solidification. The effects of re-melting temperature and dwelling time on the microstructures of the SLS-fabricated filaments were studied. The results demonstrated that the minimum requirements of re-melting temperature and dwelling time for sufficient treatment were 65 °C and 5 min respectively and the size of the SLS-fabricated filaments was reduced from 683.3 ± 28.0 µm to 601.6 ± 17.4 µm. This method was also highly effective in treating three-dimensional (3D) PCL lattice scaffolds, which showed improved filament quality and mechanical properties after post-treatment. The treated PCL scaffolds with an initial compressive modulus and strength of 3027.8 ± 204.2 kPa and 208.8 ± 14.5 kPa can maintain their original shapes after implantation in vivo for 24 weeks. Extensive newly-grown tissues were found to gradually penetrate into the porous regions along the PCL filaments. Although degradation occurred, the mechanical properties of the implanted constructs stably maintained. The presented method provides an innovative, green and general post-treatment strategy to improve both the filament quality and mechanical properties of SLS-fabricated PCL scaffolds for various tissue engineering applications.

Oral myiasis after cerebral infarction in an elderly male patient from southern China: A case report.

BACKGROUND: Myiasis is a rare but risky pathology caused by a parasitic infestation of humans and animals by the dipterous larva. Oral myiasis occurs when soft tissues of the oral cavity are invaded by the larvae of flies. It is not a common disease for the reason that the oral cavity is not easily reachable for the fly to lay eggs. But it can cause pain, infection, uncomfortable feeling when the worms move, tissue destruction and/or even life-threatening hemorrhages. CASE SUMMARY: We reported a case of oral myiasis after cerebral infarction in a 78-year-old male patient from southern China (Guangdong Zhanjiang). As a result of cerebral infarction, he suffered from right hemiplegia, mobility and mental decline for about 3 mo. He had difficulty swallowing and was fed via a feeding tube. He mostly engaged in mouth breathing and had poor oral and dental hygiene. More than 20 live larvae were collected from the patient's oral cavity, which were localized in the maxillary gingiva, the mandibular gingiva and the tongue. The patient recovered after the routine oral cleaning, removal of maggots, debridement and anti-infection treatment. CONCLUSION: Early diagnosis and treatment of this infestation are essential due to the bothersome symptoms, such as inflammation, intense anxiety over the larvae movement, possible serious complications, etc. Clinical staff should be familiar with this infestation, and this disease should be considered, especially in physically and mentally disabled patients or those at significant risk for infection. Necessary measures, including good sanitation, personal and environmental hygiene and special care should be adopted so as to prevent this disease.

Enhanced corrosion resistance and bonding strength of Mg substituted ß-tricalcium phosphate/Mg(OH)2 composite coating on magnesium alloys via one-step hydrothermal method.

To overcome the defect of high degradation rate of magnesium (Mg), bioactive coatings with compact structure, sufficient bonding strength and enhanced corrosion resistance are essential for Mg-based biodegradable implants. In this study, a dense Mg-substituted ß-tricalcium phosphate and magnesium hydroxide (ß-TCMP/Mg(OH)2) composite coating was prepared on AZ31 alloy via one-step hydrothermal method. The influences of hydrothermal temperature on its composition, microstructure of the surface and interface, bonding strength and corrosion behavior were evaluated. The results showed that the compact composite coating synthesized at 140 °C not only possessed a crack-free bilayered structure with an adequate bonding strength (more than 20.88 ±â€¯1.60 MPa), but also got an extreme high impedance (1197.003 ±â€¯152.817 kΩ cm2) so that significantly enhanced the corrosion resistance and inhibited the formation of pitting corrosion. Furthermore, the in vitro immersion test suggested that the composite coating slower the initial degradation rate of Mg alloys and enhanced its surface bioactivity to some extent.

Synthesis and characterization of magnesium phytic acid/apatite composite coating on AZ31 Mg alloy by microwave assisted treatment.

To improve the corrosion resistance and bioactivity of AZ31 magnesium alloy, a crack-free magnesium phytic acid/apatite composite coating was synthesized on AZ31 substrate via chemical conversion deposition and followed a rapid microwave assisted treatment. The influences of pH values of the microwave solution on the morphology, composition and corrosion resistance properties of the composite coating were investigated. An apatite coating with bilayer structure was completely covered the magnesium phytic acid conversion coating after microwave radiation in the solution of pH 6.5, which reached the thickness of ~7.0 µm. During the electrochemical and immersion tests in simulated body fluid (SBF), the samples with composite coating exhibited a remarkably improved corrosion resistance, slower degradation rate and rapid inducing of Ca-P apatite deposition, suggesting that the composite coating could provide a long-time protection for substrates and promote the bioactivity of AZ31 magnesium alloys. Moreover, after 5 days of incubation, the composite coating showed non-cytotoxicity, good osteoblast adhesion and proliferation.

Treatment of hepatoma with liposome-encapsulated adriamycin administered into hepatic artery of rats.

AIM: To observe the therapeutic effects of liposome-encapsulated adriamycin (LADM) on hepatoma in comparison with adriamycin solution (FADM) and adriamycin plus blank liposome (ADM + BL) administered into the hepatic artery of rats. METHODS: LADM was prepared by pH gradient-driven method. Normal saline, FADM (2 mg/kg), ADM+BL (2 mg/kg), and LADM (2 mg/kg) were injected via the hepatic artery in rats bearing liver W256 carcinosarcoma, which were divided into four groups randomly. The therapeutic effects were evaluated in terms of survival time, tumor enlargement ratio, and tumor necrosis degree. The difference was determined with ANOVA and Dunnett test and log rank test. RESULTS: Compared to FADM or ADM + BL, LADM produced a more significant tumor inhibition (tumor volume ratio: 1.243 +/- 0.523 vs 1.883 +/- 0.708, 1.847 +/- 0.661, P < 0.01), and more extensive tumor necrosis. The increased life span was prolonged significantly in rats receiving LADM compared with FADM or ADM+BL (231.48 vs 74.66, 94.70) (P < 0.05). CONCLUSION: The anticancer efficacies of adriamycin on hepatoma can be strongly improved by liposomal encapsulation through hepatic arterial administration.

Lymphatic chemotherapy induces apoptosis in lymph node metastases in a rabbit breast carcinoma model.

The purpose of the study was to evaluate the potential of lymphatic chemotherapy in inducing apoptosis in axillary lymph node metastases in a rabbit breast cancer model. A total of 30 female New Zealand rabbits with mammary implantation of VX2 carcinomas were divided into three groups randomly, with ten in each. Treatment was carried out once axillary lymph node reached 5 mm in the maximum diameter. Group A received a subcutaneous injection of liposomal adriamycin (LADR) adjacent to the breast tumor. Group B received free adriamycin (FADR) administered into the auricular vein. Group C received a sham treatment. The dose of adriamycin in each administration was 1 mg/kg in groups A and B. Treatment was repeated every 48 h. Axillary lymph nodes were dissected out 48 h after the third treatment. The nodal sizes before and after the treatment were measured. The therapeutic effect was evaluated in terms of the node volume ratio and apoptotic index (AI) of metastatic cells in nodes identified with TUNEL technique. The significance of difference was determined with one-way ANOVA followed by the Fischer LSD test. Compared to group C, the enlargement of lymph nodes was sufficiently slowed down in both groups A and B, and group A showed a further strong inhibitory effect than group B (P = 0.002). Apparent VX2 cell apoptosis was detected in the lymph nodes of groups A and B. The average AI in group B (15.31%) was significantly higher than in group C (5.16%). The highest AI was found in animals of group A (21.73%), with a further significant difference from group B (P = 0.000). These data suggest that lymphatic chemotherapy appears to be a promising method to induce apoptosis in lymph node metastases

[Treatment of rabbits bearing advanced VX2 tumors in the mammary gland with nano-sized liposomal adriamycin administered by various routes].

OBJECTIVE: To investigate the therapeutic effect of nano-sized liposomal adriamycin (NLADR) administered by various routes on rabbits bearing advanced breast tumors. METHODS: NLADR with a mean diameter of 120 nm was prepared by pH gradient-driven drug encapsulation method. VX(2) tumor mass suspension was injected into the breast tissues of 50 female New Zealand White rabbits. Six weeks after the inoculation 38 surviving tumor-bearing rabbits were randomly divided into 5 groups: group A (control group), receiving a sham treatment; group B, receiving subcutaneous injection of NLADR with a dose of 1 mg/kg into the areas adjacent to the implanted tumor; group C, receiving intravenous injection of NLADR with a dose of 1 mg/kg; group D, receiving NLADR with a dose of 1 mg/kg administered by subcutaneous injection combined with intravenous injection with half of the whole dose for both routes; and group E, receiving intravenous injection of free adriamycin (FADR). The treatment was repeated every 48 hours. The rabbits were killed 48 hours after the third treatment. The breast tumors, axillary lymph nodes, and all of the metastatic tumors anatomically detected in distant organs were collected. The sizes of tumors and axillary nodes before and after treatment were measured. Necrosis of tumor tissue was assessed pathologically. The mRNA expression of proliferating cell nuclear antigen (PCNA) was determined using RT-PCR. Apoptosis was identified and quantified as apoptosis index (AI) using TUNEL method. RESULTS: The average growth rate of tumor was the highest in group A (1.58) and the lowest in group C (1.33). The average growth rate of axillary lymph nodes was the highest in group A (3.70), significantly higher than in any other groups (all P = 0.00); and was the lowest in group B, significantly lower than groups A, C, and E (all P < 0.01), however without a significant difference between groups B and D (P = 0.148). The PCNA mRNA expression level of the implanted tumor in groups C was the lowest, significant lowest then those in group A and B (both P < 0.01). The sequence of PCNA mRNA in the axillary lymph nodes was group B < group D < group C < group E < group A with significant differences between group B and groups A, C, and E. The sequence of PCNA mRNA in the mediastinal lymph nodes was group B < Group E < group D < group C < group A. The PCNA mRNA expression level was the lowest in group D, significantly lower than that in group A (P = 0.011). Necrosis of implanted tumor, metastatic foci in lung and liver, and lymph nodes was obvious in groups C, D, and E. Necrosis of implanted tumor and metastatic foci in lung and liver was significantly obvious in group C than in group D (P = 0.000 and P = 0.022). Necrosis of the implanted tumor was significantly more obvious in group C than in group F (P = 0.033). Necrosis of axillary lymph nodes was significantly more obvious in group than in groups C and E (P = 0.000 and P = 0.000). The values of AI of the implanted tumor in groups C and D were 16.74% and 18.04%, both significantly higher than those in group E (P = 0.02 and P = 0.04), and those of group E were significantly higher than those in groups A and B (both P < 0.01). The AI value of the axillary lymph nodes was 21.73%, significantly than those in groups A, C, and E (all P < 0.01). The average AI values of the metastatic foci were 16.52%, 15.77%, and 14.50%, all significantly higher than that in group B (all P < 0.01), and that of group B was significantly higher than that in group A (P = 0.039). CONCLUSION: NLADR, especially intravenous administration combined with subcutaneous administration, is effective in treatment of advanced breast carcinoma with lymphatic and distant metastases.