Surface-Coated Cerium Nanoparticles to Improve Chemotherapeutic Delivery to Tumor Cells.

The antioxidant property of cerium oxide nanoparticles has increased their demand as a nanocarrier to improve the delivery and therapeutic efficacy of anticancer drugs. Here, we report the synthesis of alginate-coated ceria nanoformulations (ceria NPs) and characterization using FTIR spectroscopy, Raman microscopy, and X-ray diffraction. The synthesized ceria NPs show negligible inherent in vitro toxicity when tested on a MDA-MB-231 breast cancer cell line at higher particle concentrations. Upon loading these particles with doxorubicin (Dox) and paclitaxel (PTX) drugs, we observe a potential synergistic cytotoxic effect mediated by the drug and the ceria NPs, resulting in the better killing capacity as well as suppression of cell migration against the MDA-MB-231 cell line. Further, to verify the immune-escaping capacity before targeting cancer cells, we coated the drug-loaded ceria NPs with the membrane of MDA-MB-231 cells using an extrusion method. The resultant delivery system exhibited in vitro preferential uptake by the MDA-MB-231 cell line and showed reduced uptake by the murine macrophage cell line (RAW 264.7), assigning its potential application as non-immunogenic personalized therapy in targeting and killing of cancer cells.

Magnetic nanofibers based bandage for skin cancer treatment: a non-invasive hyperthermia therapy.

BACKGROUND: The treatment of non-melanoma skin cancer and deadliest malignant melanoma skin cancer are the fifth and ninth most expensive treatments in Medicare, respectively. Moreover, the recurrence of cancer after currently available therapies, that is, surgery or radiotherapy, reduces the patient's life expectancy. AIMS: In view of this, we fabricated magnetic nanofibrous mat-based bandage to treat skin cancer non-invasively using an external alternating current (AC) magnetic field induced hyperthermia. METHODS: The Fe3 O4 nanoparticles incorporated polycaprolactone (PCL) fibers based bandages were fabricated using the electrospinning technique. The efficacy of the bandage was investigated in vitro using parental/doxorubicin hydrochloride (Dox)-resistant HeLa cells and in vivo using BALB/c mouse model in the presence of an external AC magnetic field (AMF). RESULTS: The PCL-Fe3 O4 fibrous mat-based bandages dissipate heat energy locally on the application of an external AMF and increase the surrounding temperature in a controlled way up to 45°C in a few mins. The in vitro study confirms the elevated temperature could kill parental and Dox-resistant HeLa cells significantly. As the activity of Dox enhanced at a higher temperatures, more than 85% of parental HeLa cells were dead when cells incubated with Dox contained fibrous mat in the presence of AMF for 10 minutes. Further, we confirm the full recovery of chemically induced skin tumors on BALB/c mice within a month after five hyperthermic doses for 15 minutes. Also, there was no sign of inflammation and recurrence of cancer post-therapy. CONCLUSION: The present study confirms the PCL-Fe3 O4 nanofibrous based bandages are unique and compelling to treat skin cancer.

A Novel Ex Vivo System Using 3D Polymer Scaffold to Culture Circulating Tumor Cells from Breast Cancer Patients Exhibits Dynamic E-M Phenotypes.

The majority of the cancer-associated deaths is due to metastasis-the spread of tumors to other organs. Circulating tumor cells (CTCs), which are shed from the primary tumor into the circulation, serve as precursors of metastasis. CTCs have now gained much attention as a new prognostic and diagnostic marker, as well as a screening tool for patients with metastatic disease. However, very little is known about the biology of CTCs in cancer metastasis. An increased understanding of CTC biology, their heterogeneity, and interaction with other cells can help towards a better understanding of the metastatic process, as well as identify novel drug targets. Here we present a novel ex vivo 3D system for culturing CTCs from breast cancer patient blood samples using porous poly(ε-caprolactone) (PCL) scaffolds. As a proof of principle study, we show that ex vivo culture of 12/16 (75%) advanced stage breast cancer patient blood samples were enriched for CTCs identified as CK+ (cytokeratin positive) and CD45- (CD45 negative) cells. The deposition of extracellular matrix proteins on the PCL scaffolds permitted cellular attachment to these scaffolds. Detection of Ki-67 and bromodeoxyuridine (BrdU) positive cells revealed proliferating cell population in the 3D scaffolds. The CTCs cultured without prior enrichment exhibited dynamic differences in epithelial (E) and mesenchymal (M) composition. Thus, our 3D PCL scaffold system offers a physiologically relevant model to be used for studying CTC biology as well as for individualized testing of drug susceptibility. Further studies are warranted for longitudinal monitoring of epithelial-mesenchymal transition (EMT) in CTCs for clinical association.