Preferential uptake of antibody targeted calcium phosphosilicate nanoparticles by metastatic triple negative breast cancer cells in co-cultures of human metastatic breast cancer cells plus bone osteoblasts.

Calcium phosphosilicate nanoparticles (CPSNPs) are bioresorbable nanoparticles that can be bioconjugated with targeting molecules and encapsulate active agents and deliver them to tumor cells without causing damage to adjacent healthy tissue. Data obtained in this study demonstrated that an anti-CD71 antibody on CPSNPs targets these nanoparticles and enhances their internalization by triple negative breast cancer cells in-vitro. Caspase 3,7 activation, DNA damage, and fluorescent microscopy confirmed the apoptotic breast cancer response caused by targeted anti-CD71-CPSNPs encapsulated with gemcitabine monophosphate, the active metabolite of the chemotherapeutic gemcitabine used to treat cancers including breast and ovarian. Targeted anti-CD71-CPSNPs encapsulated with the fluorophore, Rhodamine WT, were preferentially internalized by breast cancer cells in co-cultures with osteoblasts. While osteoblasts partially internalized anti-CD71-GemMP-CPSNPs, their cell growth was not affected. These results suggest that CPSNPs may be used as imaging tools and selective drug delivery systems for breast cancer that has metastasized to bone.

Effective encapsulation and biological activity of phosphorylated chemotherapeutics in calcium phosphosilicate nanoparticles for the treatment of pancreatic cancer.

Drug resistant cancers like pancreatic ductal adenocarcinoma (PDAC) are difficult to treat, and nanoparticle drug delivery systems can overcome some of the limitations of conventional systemic chemotherapy. In this study, we demonstrate that FdUMP and dFdCMP, the bioactive, phosphorylated metabolites of the chemotherapy drugs 5-FU and gemcitabine, can be encapsulated into calcium phosphosilicate nanoparticles (CPSNPs). The non-phosphorylated drug analogs were not well encapsulated by CPSNPs, suggesting the phosphate modification is essential for effective encapsulation. In vitro proliferation assays, cell cycle analyses and/or thymidylate synthase inhibition assays verified that CPSNP-encapsulated phospho-drugs retained biological activity. Analysis of orthotopic tumors from mice treated systemically with tumor-targeted FdUMP-CPSNPs confirmed the in vivo up take of these particles by PDAC tumor cells and release of active drug cargos intracellularly. These findings demonstrate a novel methodology to efficiently encapsulate chemotherapeutic agents into the CPSNPs and to effectively deliver them to pancreatic tumor cells.

Synthesis of In2O3@SiO2 core-shell nanoparticles with enhanced deeper energy level emissions of In2O3.

In(2)O(3)@SiO(2) core-shell nanoparticles were prepared using an organic solution synthesis approach and reverse-microemulsion technique. In order to explore the availability of various silica encapsulations, a partial phase diagram for this ternary system consisting of hexane/cyclohexane (1:29 wt), surfactant (polyoxyethylene(5)nonylphenyl ether, i.e., Igepal CO-520), and aqueous solution containing ammonium hydroxide was also established. It is realized that the shell-thickness can be tuned by several parameters such as the concentration of In(2)O(3) nanocrystal suspension and the dose of the Si-precursor, tetraethyl orthosilicate. It was observed that the deeper energy level emissions of In(2)O(3) were apparently enhanced when In(2)O(3) was confined by the silica-shell in such core-shell nanoparticles. However, this enhancement could be degraded by increasing the shell-thickness.

The use of nanoparticulates to treat breast cancer.

Breast cancer is a major ongoing public health issue among women in both developing and developed countries. Significant progress has been made to improve the breast cancer treatment in the past decades. However, the current clinical approaches are invasive, of low specificity and can generate severe side effects. As a rapidly developing field, nanotechnology brings promising opportunities to human cancer diagnosis and treatment. The use of nanoparticulate-based platforms overcomes biological barriers and allows prolonged blood circulation time, simultaneous tumor targeting and enhanced accumulation of drugs in tumors. Currently available and clinically applicable innovative nanoparticulate-based systems for breast cancer nanotherapies are discussed in this review.

A Cholecystokinin B Receptor-Specific DNA Aptamer for Targeting Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinomas (PDACs) constitutively express the G-protein-coupled cholecystokinin B receptor (CCKBR). In this study, we identified DNA aptamers (APs) that bind to the CCKBR and describe their characterization and targeting efficacy. Using dual SELEX selection against "exposed" CCKBR peptides and CCKBR-expressing PDAC cells, a pool of DNA APs was identified. Further downselection was based on predicted structures and properties, and we selected eight APs for initial characterizations. The APs bound specifically to the CCKBR, and we showed not only that they did not stimulate proliferation of PDAC cell lines but rather inhibited their proliferation. We chose one AP, termed AP1153, for further binding and localization studies. We found that AP1153 did not activate CCKBR signaling pathways, and three-dimensional Confocal microscopy showed that AP1153 was internalized by PDAC cells in a receptor-mediated manner. AP1153 showed a binding affinity of 15 pM. Bioconjugation of AP1153 to the surface of fluorescent NPs greatly facilitated delivery of NPs to PDAC tumors in vivo. The selectivity of this AP-targeted NP delivery system holds promise for enhanced early detection of PDAC lesions as well as improved chemotherapeutic treatments for PDAC patients.

Incorporating Informatics for Integrating Biology and the Bedside (i2b2) into Predoctoral Trainee Curriculum to Evaluate Student-Generated Hypotheses.

As part of the Clinical and Translational Science Institute predoctoral TL1 training program at the Pennsylvania State University, a multidisciplinary team of predoctoral trainees representing the Chemistry, Neurosurgery, Nutritional Sciences, and Public Health Sciences departments were introduced to the NIH-sponsored Informatics for Integrating Biology and the Bedside (i2b2) database to test the following student-generated hypothesis: children with iron deficiency anemia (IDA) are at increased risk of attention deficit-hyperactivity disorder (ADHD). Children aged 4-12 and 4-17 years were categorized into IDA and control groups. De-identified medical records from the Penn State Milton S. Hershey Medical Center (HMC) and the Virginia Commonwealth University Medical Center (VCUMC) were used for the analysis. Overall, ADHD prevalence at each institution was lower than 2011 state estimates. There was a significant association between IDA and ADHD in the 4-17-year-old age group for all children (OR: 1.902 [95% CI: 1.363-2.656]), Caucasian children (OR: 1.802 [95% CI: 1.133-2.864]), and African American children (OR: 1.865 [95% CI: 1.152-3.021]). Clinical and Translational Science Award (CTSA) infrastructure is particularly useful for trainees to answer de novo scientific questions with minimal additional training and technical expertise. Moreover, projects can be expanded by collaborating within the CTSA network.

Novel strategies for managing pancreatic cancer.

With the incidence reports of pancreatic cancer increasing every year, research over the last several decades has been focused on the means to achieve early diagnosis in patients that are at a high risk of developing the malignancy. This review covers current strategies for managing pancreatic cancer and further discusses efforts in understanding the role of early onset symptoms leading to tumor progression. Recent investigations in this discussion include type 3c diabetes, selected biomarkers and pathways related to pancreatic intraepithelial neoplasia lesions, drug resistance, and advances in nanomedicine which may provide significant solutions for improving early detection and treatments in future medicine.