Hybrid Polyelectrolyte Nanocomplexes for Non-Viral Gene Delivery with Favorable Efficacy and Safety Profile.

The development of nanovectors for precise gene therapy is increasingly focusing on avoiding uncontrolled inflammation while still being able to effectively act on the target sites. Herein, we explore the use of non-viral hybrid polyelectrolyte nanocomplexes (hPECs) for gene delivery, which display good transfection efficacy coupled with non-inflammatory properties. Monodisperse hPECs were produced through a layer-by-layer self-assembling of biocompatible and biodegradable polymers. The resulting nanocomplexes had an inner core characterized by an EGFP-encoding plasmid DNA (pDNA) complexed with linear polyethyleneimine or protamine (PEI or PRM) stabilized with lecithin and poly(vinyl alcohol) (PVA) and an outer layer consisting of medium-molecular-weight chitosan (CH) combined with tripolyphosphate (TPP). PEI- and PRM-hPECs were able to efficiently protect the genetic cargo from nucleases and to perform a stimuli-responsive release of pDNA overtime, thus guaranteeing optimal transfection efficiency. Importantly, hPECs revealed a highly cytocompatible and a non-inflammatory profile in vitro. These results were further supported by evidence of the weak and unspecific interactions of serum proteins with both hPECs, thus confirming the antifouling properties of their outer shell. Therefore, these hPECs represent promising candidates for the development of effective, safe nanotools for gene delivery.

Nanoparticles for Diagnosis and Target Therapy in Pediatric Brain Cancers.

Pediatric brain tumors represent the most common types of childhood cancer and novel diagnostic and therapeutic solutions are urgently needed. The gold standard treatment option for brain cancers in children, as in adults, is tumor resection followed by radio- and chemotherapy, but with discouraging therapeutic results. In particular, the last two treatments are often associated to significant neurotoxicity in the developing brain of a child, with resulting disabilities such as cognitive problems, neuroendocrine, and neurosensory dysfunctions/deficits. Nanoparticles have been increasingly and thoroughly investigated as they show great promises as diagnostic tools and vectors for gene/drug therapy for pediatric brain cancer due to their ability to cross the blood-brain barrier. In this review we will discuss the developments of nanoparticle-based strategies as novel precision nanomedicine tools for diagnosis and therapy in pediatric brain cancers, with a particular focus on targeting strategies to overcome the main physiological obstacles that are represented by blood-brain barrier.

Biomimetic Nanocarriers for Cancer Target Therapy.

Nanotechnology offers innovative tools for the design of biomimetic nanocarriers for targeted cancer therapy. These nano-systems present several advantages such as cargo's protection and modulation of its release, inclusion of stimuli-responsive elements, and enhanced tumoral accumulation. All together, these nano-systems suffer low therapeutic efficacy in vivo because organisms can recognize and remove foreign nanomaterials. To overcome this important issue, different modifications on nanoparticle surfaces were exploited in order to reach the desired therapeutic efficacy eliciting, also, the response of immune system against cancer cells. For this reason, more recently, a new strategy involving cell membrane-covered nanoparticles for biomedical application has been attracting increasing attention. Membranes from red blood cells, platelets, leukocytes, tumor, and stem cells, have been exploited as biomimetic coatings of nanoparticles for evading clearance or stimulated immune system by maintaining in the same way their targeting capability. In this review, the use of different cell sources as coating of biomimetic nanocarriers for cancer therapy is discussed.