Paragraph: this work presents a simple one-pot protocol to achieve core-doped shell nanohybrids comprising silver nanoparticles, curcumin and thermoresponsive polymeric shell taking advantage of the reducing properties of phenolic curcumin substance and its ability to decorate metallic surfaces. Silver nanoparticles were synthesized, via sodium citrate and silver nitrate addition into a boiling aqueous solution of curcumin, monomers and surfactant. curcumin and sodium citrate promoted silver nucleation, acting as reducing and stabilizing agents. these curcumin-capped Agnps enabled, after adding the radical polymerization initiator, the assembling of the growing polymer chains around the hydrophobic Agnp surface. the resultant core-doped shell nanohybrids exhibit plasmonic, luminescent and volume thermoresponsive properties, with improved possibilities to be used as successful therapeutic platforms. In fact, the possibility to nanoconfine the synergistic antioxidant, antiviral, antibacterial features of silver and curcumin in one bioavailable hybrid paves the way to promising applications in the biomedical field. The exciting electronic, optical, catalytic and antimicrobial properties of metal NPs can be stymied by their tendency to aggregate. To overcome this issue and provide metallic nanoparticles with additional features, the hybridization with polymeric materials is a successful strategy. In this regard, polymer micro/nanogels exhibit high colloidal stability, great versatility in their chemical and topological composition, drug loading and functionalization capabilities 1 that make them unique vehicles and reservoirs for metal nanoparticles 2,3 . Additionally, the permeability of the gel-system coating allows a controlled loading and release of bioactive molecules and drugs. Furthermore, polymer microgels are frequently used as nanoreactors for the in situ synthesis of metallic NPs 4 , and small particles decorating the microgel are successfully formed 5 . However, the control over the metallic NP structure and distribution is rather difficult. Core-shell hybrid nanogels usually face metal@polymer nanohybrid synthesis from a different point of view; and the most reported protocols are based on the polymer self-assembling around a preformed metal NP. The ligand exchange using polymers with functional groups able to attach the metal NP is a successful approach to attain thin polymer shells 6 . However to achieve polymer coating with tunable thickness, polymerization in heterogeneous media, as free radical precipitation polymerization (FRPP) is the most widely choice 7,8 . Since this technique relies on the precipitation of water insoluble growing polymer chain, a previous surface preparation of metal NP is required. Note that the organic polymer is not compatible with the anionic citrate ligand, commonly used to synthesize metal NPs, in aqueous medium 9,10 . Therefore a variety of strategies can be found in the literature, mainly for gold 7, 8, [11] [12] [13] [14] [15] , whereas works focused on achieving silver@polymer core-shell nanogels are scarce; despite the reliable properties of silver NPs in applications as ultrasensitive analysis of molecules through Surface Enhanced Raman Spectroscopy (SERS) 2,16 , catalysis 17 , cancer cell imaging 16,18 and other applications related to their antimicrobial properties 19 . Recently, we developed one-step protocol supporting core-shell hybrid nanogel synthesis, regardless of the monomer polarity. The strategy was based on the use of hydrophobic thiolated methacrylate monomer as compatible bridge between the as-synthesized Au@citrate surface and the growing polymer chains 14 . The modification of the metal surface with the hydrophobic compound led to effective polymer self-assembling around the inorganic core. Thus, we envisioned, in this work, that hydrophobic molecules as curcumin (Fig. 1A) , having a two-fold function, as reducing agent in silver NP synthesis as well as diminishing the interfacial energy between the growing polymer chain and the metallic surface, might trigger the core-shell hybrid NP assembly. Previous backgrounds evidenced the curcumin ability to reduce Ag + and Au 3+ ions to silver 20-22 and gold 23 nanoparticles, without any other additional reductant or in the presence of citrate and CTBA to modulate NP shape 24 . Thus, Kundu and Nithiyanantham 20 , in a pioneer work, were able to synthesize different shapes of AgNP (spheres, nanowires and anisotropic nanoflakes) by tuning the molar ratio of curcumin to AgNO 3 . Nevertheless, even though the reductant ability of curcumin has been already reported, it should be noted that, as far as we know, none has postulated that hydrophobic curcumin presence nearby metal surface may facilitate polymer self-assembling during post-crosslinking polymerization. In addition, by considering the antioxidant properties of this natural phenolic compound, our curcumin-promoted Ag@nanogel hybrid system will state a double benefit arising from the biomedical properties of curcumin itself, as antibacterial, self-healing 25,26 , antiviral 27 and anti-inflammatory 28 ; and from the antibacterial 19 synergistic effect and remarkable antiviral 29 activity of particles comprising silver nanoparticles and curcumin in one hybrid. Moreover, encapsulation of curcumin in the hydrophobic polymer shell will increase curcumin bioavailability protecting curcumin from hydrolytic degradation 30 , since this is the main limitation for its therapeutic applications. experimental Materials. The monomer 2-(2-methoxyethoxy)ethyl methacrylate (MEO 2 MA) (Aldrich 95%) was purified by passing through a neutral alumina column. Tetraethylene glycol dimethacrylate (TEGDMA) (≥90%), trisodium citrate dihydrate (≥98%) and silver nitrate (AgNO 3 ) (99.99%) were purchased from Aldrich. Sodium dodecyl sulfate (SDS) (≥97%) and ammonium persulfate (APS) (>98%), were purchased from Fluka. Curcumin (≥98%) was obtained from Acros Organics. All chemical reagents were employed as received. The solvents used, ethanol and water, were analytical and Milli-Q grade, respectively. 
 Title: curcumin to promote the Synthesis of Silver nps and their Self- Assembly with a thermoresponsive polymer in core-Shell nanohybrids
Output: True