Abstract

The hook and claw assembly is the core moving part of the control rod drive mechanism. The various actions of the control...

Highlights

  • Extracellular and Intracellular Barriers in Systemic small interfering RNAs (siRNAs) Delivery to Solid TumorsVarious delivery vehicles have been developed for systemic delivery of therapeutic siRNA into solid tumors [1]

  • Several multimolecular delivery vehicles are under clinical trial for RNAi-based cancer therapy but the dose amounts of siRNA (0.1-1.5mg/kg) are comparatively higher than levels observed in diseases of other organs (e.g. 0.15-0.3mg/kg in the liver)

  • This may indicate that the highest expected RNAi efficacy in tumor is similar with that in the liver

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Summary

Introduction

Extracellular and Intracellular Barriers in Systemic siRNA Delivery to Solid Tumors. Various delivery vehicles have been developed for systemic delivery of therapeutic siRNA into solid tumors [1]. Naked siRNAs with a size of approximately 7nm in length and 2 nm in diameter [3], as well as their degraded products, can be readily filtered within 10 min through GBM and passed into urine [4,5]. These facts generate the lower size limitation of approximately 10 nm for design of delivery vehicles. Only 30nmsized nanoparticles accomplished significant antitumor activity in the pancreatic tumor model [13] These facts have encouraged researchers to engineer smaller delivery vehicles with a size of less than 50nm for enhanced accumulation in heterogeneous tumor tissues. The EPR effect observed in animal models needs to be carefully interpreted for the translation to clinical settings as described in other reviews [22,23,24]

Design Criteria to Overcome Extracellular Barriers
Design Criteria to Overcome Intracellular Barriers
Design of siRNA Delivery Vehicles
Methods in Monomer Components
Delivery vehicle contains acidic pH responsiveness for faster dissociation
Conclusion

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