Biodegradable nano-architectures containing gold nanoparticles arrays
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Biodegradable nano-architectures containing gold nanoparticles arrays Domenico Cassano,1,2 Diego Rota Martir,2 Giovanni Signore,2 Cinzia Avigo,3 Luca Menichetti,3 Vincenzo Piazza,2 and Valerio Voliani*,2 1 NEST-Scuola Normale Superiore, P.zza San Silvestro, 12 - 56126, Pisa (PI), Italy 2 Center for Nanotechnology Innovation @NEST, Istituto Italiano di Tecnologia, P.zza San Silvestro, 12 - 56126, Pisa (PI), Italy 3 Istituto di fisiologia clinica, CNR-IFC, Pisa (PI), Italy *Corresponding Author: Valerio Voliani ([email protected]) ABSTRACT One of the major concerns regarding the clinical translation of metal nanoparticles is related to the question of their persistence in organisms that can increase the likelihood of toxicity and the interaction/interference with common medical diagnoses. In order to overcome these issues we have recently introduced a versatile 90 nm nanoarchitecture composed by: i) arrays of 3 nm gold nanoparticles, ii) functionalizable commercial polymers surrounding the gold nanoparticles, and iii) biodegradable and derivatizable silica shell embedding the polymer-nanoparticle assembly. These robust nanocapsules maintain the intriguing features of gold nanospheres but are biodegraded in physiological media to their potentially renal clearable building blocks. INTRODUCTION One of the unique aspects of nanoparticles stems from the possibility to engineer their geometry and surface coating to achieve peculiar chemical, physical and physiological features, allowing simultaneous targeting, diagnostic, and therapeutic functionality which can be chemically tailored for a specific patient or disease.[1–3] It is worth noticing that the average diameter of most of the metal inorganic nanoparticles proposed for in vivo cancer therapy and multimodal applications is usually over 20 nm.[4,5] The most efficient clearance pathway is through renal excretion, which is controlled by glomerular filtration and shows a threshold of maximum 6 nm.[1] Excretion routes for larger objects can be through liver and spleen into bile and feces but, unfortunately, the excretion of intact metal nanoparticles from these pathways is an extremely slow and inefficient process, leading to unwanted accumulation which in turns causes increased toxicity and interference with common medical diagnoses.[6,7] It is important to notice that US Food and Drug Administration requires that agents injected into the human body should be cleared completely in a reasonable amount of time, avoiding persistence in the organism.[7] This requisite is currently not fulfilled by any metal based nanoparticle.[4] On the other hand, nanoparticles with a diameter of few nanometers would show ideallyfast clearance kinetics through renal excretion,[7,8] but it should be noted that excessively fast clearance hampers their therapeutic and diagnostic applications.[1] Moreover, the physical and chemical properties of metal nanoparticles strongly depend on their size.[9] Thus, the behavior shown by nanostructures above 20 nm size range is usually lost or altered
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