Nanocarrier-mediated siRNA delivery:a new approach for the treatment of traumatic brain injury-related Alzheimer's disease

Traumatic brain injury and Alzheimer's disease share pathological similarities,including neuronal loss,amyloid-βdeposition,tau hyperphosphorylation,blood-brain barrier dysfunction,neuroinflammation,and cognitive deficits.Furthermore,traumatic brain injury can exacerbate Alzheimer's disease-like pathologies,potentially leading to the development of Alzheimer's disease.Nanocarriers offer a potential solution by facilitating the delive ry of small interfering RNAs across the blood-brain barrier for the targeted silencing of key pathological genes implicated in traumatic brain injury and Alzheimer's disease.U nlike traditional approaches to neuro regeneration,this is a molecula r-targeted strategy,thus avoiding non-specific drug actions.This review focuses on the use of nanocarrier systems for the efficient and precise delive ry of siRNAs,discussing the advantages,challenges,and future directions.In principle,siRNAs have the potential to target all genes and non-targetable protein s,holding significant promise for treating various diseases.Among the various therapeutic approaches currently available for neurological diseases,siRNA gene silencing can precisely"turn off"the expression of any gene at the genetic level,thus radically inhibiting disease progression;however,a significant challenge lies in delivering siRNAs across the blood-brain barrier.Nanoparticles have received increasing attention as an innovative drug delive ry tool fo r the treatment of brain diseases.They are considered a potential therapeutic strategy with the advantages of being able to cross the blood-brain barrier,targeted drug delivery,enhanced drug stability,and multifunctional therapy.The use of nanoparticles to deliver specific modified siRNAs to the injured brain is gradually being recognized as a feasible and effective approach.Although this strategy is still in the preclinical exploration stage,it is expected to achieve clinical translation in the future,creating a new field of molecular targeted therapy and precision medicine for the treatment of Alzheimer's disease associated with traumatic brain injury.

Nanoparticles carrying neurotrophin-3-modified Schwann cells promote repair of sciatic nerve defects

Schwann ceils and neurotrophin-3 play an important role in neural regeneration, but the secretion of neurotrophin-3 from Schwann cells is limited, and exogenous neurotrophin-3 is inactived easily in vivo. In this study, we have transfected neurotrophin-3 into Schwann cells cultured in vitro using nanoparticle liposomes. Results showed that neurotrophin-3 was successfully transfected into Schwann cells, where it was expressed effectively and steadily. A composite of Schwann cells transfected with neurotrophin-3 and poly（lactic-co-glycolic acid） biodegradable conduits was transplanted into rats to repair 10-mm sciatic nerve defects. Transplantation of the composite scaffold could restore the myoelectricity and wave amplitude of the sciatic nerve by electrophysiological examination, promote nerve axonal and myelin regeneration, and delay apoptosis of spinal motor neurons. Experimental findings indicate that neurotrophin-3 transfected Schwann cells combined with bridge grafting can promote neural regeneration and functional recovery after nerve injury.

Rational design of a nonclassical liposomal nanoscale drug delivery system for innovative cancer therapy

Advanced drug delivery systems are widely considered to be powerful approaches for treating cancer and many other diseases because of their superior ability to improve pharmacokinetics,promote lesion-targeted delivery efficacy,and/or reduce the toxic effects of diverse therapeutics.Owing to the unique biomimetic structure of lipid bilayers surrounding aqueous cavities,liposomes have been found to encapsulate various therapeutics,ranging from small molecules with different hydrophobicities to biomacromolecules.With the advent of surface PEGylation,stealth liposomes with excellent in vivo long-circulating behaviors have been generated,thus these liposomes have been extensively explored for the development of liposomal drugs with greatly improved in vivo pharmacokinetic behaviors by functioning as delivery vehicles.Inspired by their successes in clinical practice,stealth liposomes have recently been utilized as the main building scaffold or surface coating layers of other nanoparticulate formulations,which are coined as nonclassical liposomal nanoscale drug delivery systems(NDDSs)in this review,to enable the rational design of nextgeneration liposomal nanomedicine.Therefore,after overviewing the latest progress in the development of conventional liposome-based nanomedicine,we will introduce the development of these nonclassical liposomal NDDSs as well as their innovative cancer treatment strategies.We will subsequently provide a critical perspective on the future development of new cancer nanomedicines based on these rationally designed nonclassical liposomal NDDSs.