pH-Responsive polymer boosts cytosolic siRNA release for retinal neovascularization therapy

Small interfering RNA(siRNA)has a promising future in the treatment of ocular diseases due to its high efficiency,specificity,and low toxicity in inhibiting the expression of target genes and proteins.However,due to the unique anatomical structure of the eye and various barriers,delivering nucleic acids to the retina remains a significant challenge.In this study,we rationally design PACD,an A-B-C type non-viral vector copolymer composed of a hydrophilic PEG block(A),a siRNA binding block(B)and a pH-responsive block(C).PACDs can self-assemble into nanosized polymeric micelles that compact siRNAs into polyplexes through simple mixing.By evaluating its pH-responsive activity,gene silencing efficiency in retinal cells,intraocular distribution,and anti-angiogenesis therapy in a mouse model of hypoxia-induced angiogenesis,we demonstrate the efficiency and safety of PACD in delivering siRNA in the retina.We are surprised to discover that,the PACD/siRNA polyplexes exhibit remarkable intracellular endosomal escape efficiency,excellent gene silencing,and inhibit retinal angiogenesis.Our study provides design guidance for developing efficient nonviral ocular nucleic acid delivery systems.

Joint Communication and Computation Optimization for Wireless Powered Mobile Edge Computing with D2D Offloading

This paper studies a wireless powered mobile edge computing(MEC)system with device-to-device(D2D)-enabled task offloading.In this system,a set of distributed multi-antenna energy transmitters(ETs)use collaborative energy beamforming to wirelessly charge multiple users.By using the harvested energy,the actively computing user nodes can offload their computation tasks to nearby idle users(as helper nodes)via D2D communication links for self-sustainable remote computing.We consider the frequency division multiple access(FDMA)protocol,such that the D2D communications of different user-helper pairs are implemented over orthogonal frequency bands.Furthermore,we focus on a particular time block for task execution,which is divided into three slots for computation task offloading,remote computing,and result downloading,respectively,at different user-helper pairs.Under this setup,we jointly optimize the collaborative energy beamforming at ETs,the communication and computation resource allocation at users and helpers,and the user-helper pairing,so as to maximize the sum computation rate(i.e.,the number of task input-bits executed over this block)of the users,subject to individual energy neutrality constraints at both users and helpers.First,we consider the computation rate maximization problem under any given user-helper pairs,for which an efficient solution is proposed by using the techniques of alternating optimization and convex optimization.Next,we develop the optimal user-helper pairing scheme based on exhaustive search and a low-complexity scheme based on greedy selection.Numerical results show that the proposed design significantly improves the sum computation rate at users,as compared to benchmark schemes without such joint optimization.