Redox responsive Pluronic micelle mediated delivery of functional siRNA: a modular nano-assembly for targeted delivery

There is an unmet need to develop strategies that allow site-specific delivery of short interfering RNA (siRNA) without any associated toxicity. To address this challenge, we have developed a novel siRNA delivery platform using chemically modified pluronic F108 as an amphiphilic polymer with a releasable bioactive disulfide functionality. The micelles exhibited thermoresponsive properties and showed a hydrodynamic size of similar to 291 nm in DLS and similar to 200-250 nm in SEM at 37 degrees C. The grafting of free disulfide pyridyl groups enhanced the transfection efficiency and was successfully demonstrated in human colon carcinoma (HCT116; 88%) and glioma cell lines (U87; 90%), non-cancerous human dermal fibroblast (HDF; 90%) cells as well as in mouse embryonic stem (mES; 54%) cells. To demonstrate the versatility of our modular nanocarrier design, we conjugated the MDGI receptor targeting COOP peptide on the particle surface that allowed the targeted delivery of the cargo molecules to human patent-derived primary BT-13 gliospheres. Transfection experiments with this design resulted in similar to 65% silencing of STAT3 mRNA in BT-13 gliospheres, while only similar to 20% of gene silencing was observed in the absence of the peptide. We believe that our delivery method solves current problems related to the targeted delivery of RNAi drugs for potential in vivo applications.Peer reviewe

Unusual presentation of rare congenital anomaly: Isolated unilateral absence of a pulmonary artery

Unilateral absence of a pulmonary artery (UAPA) is a rare defect. It may be associated with other congenital cardiovascular malformations which present at an early age. Isolated UAPA (IUAPA), i.e., without any other cardiovascular malformations, usually is asymptomatic and presents in adulthood. In infancy, IUAPA may be suspected by the presence of recurrent respiratory infections and pulmonary hypertension (PHT). Here, we present a child with IUAPA who presented with intermittent cyanosis which is unusual. Echocardiography done showed the presence of severe PHT with a patent foramen ovale (PFO) with a right to left shunt. Detailed echo revealed the absence of right pulmonary artery which was confirmed by a multislice detector computed tomography (MDCT). Infants with unexplained PHT should be screened for the possibility of IUAPA. MDCT scan and magnetic resonance imaging (MRI) can confirm the echocardiographic diagnosis. The treatment plan depends on the presence of symptoms, size of pulmonary artery, and collaterals. Early surgical or hybrid intervention may improve survival. Medical management includes treatment for congestive cardiac failure and pulmonary vasodilators for PHT. Infants with severe PHT are difficult to treat and have poor prognosis