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A class of linear and four-arm mannosylated brush copolymers based on poly(ethylene glycol) and poly(ε-caprolactone) is presented here. The synthesis through ring-opening and atom transfer radical polymerizations provided high control over molecular weight and functionality. A post-polymerization azide–alkyne cycloaddition allowed for the formation of glycopolymers with different mannose valencies (1, 2, 4, and 8). In aqueous media, these macromolecules formed nanoparticles that were able to bind lectins, as investigated by concanavalin A binding assay. The results indicate that carbohydrate–lectin interactions can be tuned by the macromolecular architecture and functionality, hence the importance of these macromolecular properties in the design of targeted anti-pathogenic nanomaterials.

Well-defined amphiphilic PCL-PEG copolymers with complex molecular architectures were synthesized through a combination of Ring Opening Polymerization (ROP) and Atom Transfer Radical Polymerization (ATRP) and used to produce self-assembled nanoparticles for drug nanoencapsulation. By varying the functionality of the initiator used for the ATRP (i.e. linear, 4-armed or multifunctional brush macroinitiators), a library of comb-like and brush block copolymers were obtained with different structure, molecular weight, and number of PEG and PCL blocks. We investigated how these parameters influenced nanoparticle self-assembly in aqueous environment, as well as the ability to encapsulate and release hydrophobic therapeutic molecules. In particular, the hydrophobic corticosteroid dexamethasone, known as a therapeutic drug with anti-inflammatory and immunosuppressive effects, was chosen as a model. The results indicate that self-assembly, final particle size and drug loading can be tuned by designing a specific macromolecular architecture, which therefore represents a key feature for the design of efficient polymer nanocarriers for drug delivery.

In the continuous search for multimodal systems with combined diagnostic and therapeutic functions, several efforts have been made to develop multifunctional drug delivery systems. In this work, through a covalent approach, a new class of fluorinated poly(lactic-co-glycolic acid) co-polymers (F-PLGA) were designed that contain an increasing number of magnetically equivalent fluorine atoms. In particular, two novel compounds, F

Free radical polymerization (FRP) is widely used in industrial processes as an efficient and versatile method to engineer polymeric nanoparticles (PNPs) of controlled size, narrowly distributed, and of well-defined surface properties. Functional Poly(e-caprolactone) (PCL) and poly(lactic acid) (PLA) can be utilized as macromonomers in FRP in combination with a co-polymerizable poly(ethylene glycol) (PEG), to achieve aqueous dispersions of PNPs composed of a hydrophobic polyester core and a hydrophilic PEG shell of tuneable size. For several industrial and biological applications, PNPs also need surface functionalization to provide specific physicochemical characteristics, including stimuli-responsiveness, and bioactivity. In this work, a flexible “grafting through” strategy based on Ring opening polymerization (ROP) and FRP was proposed to obtain engineered polyester-PEG nanoparticles functionalized with acrylate groups on the hydrophilic shell. The presence of acrylates allows a versatile surface functionalization through Michael-type addition with a thiolated ligand (peptide), in aqueous solution under physiological pH, with the advantage of high conversion and absence of reaction side products. A cysteine-containing cyclic RGD was used as model peptide for conjugation, due to its potential application as ligand for endothelial cells. Results indicated that active cell targeting can be achieved by using this surface functionalization approach.

Fluorinated hyperbranched polyether copolymers of tuneable composition and architecture were designed and synthesized to develop drug nanocarriers as well as 19F MRI contrast agents. The performance of these nanomaterials in terms of nanoparticle formation and drug (dexamethasone) loading, as well as 19F-MRI detectability, was evaluated. These polymers were obtained through controlled ring opening multibranching polymerisation, and the presence of pendant fluorinated groups was obtained by copolymerisation of glycidol and the fluorinated glycidyl ether 2-[(2,2,2-trifluoroethoxy)methyl]oxirane. By varying polymer composition and architecture during the synthesis, we controlled the key properties of the nanomaterials, including the fluorine content, drug loading, nanoparticle size, and MRI signal. The macromolecules were cytocompatible, with the ability to deliver dexamethasone on damaged kidney glomerular cells in vitro; therefore they hold promise as new generation 19F MRI nanotheranostics.

In the continuous search for multimodal systems with combined diagnostic and therapeutic functions, several efforts have been made to develop multifunctional drug delivery systems. In this work, through a covalent approach, a new class of fluorinated poly(lactic-co-glycolic acid) co-polymers (F-PLGA) were designed that contain an increasing number of magnetically equivalent fluorine atoms. In particular, two novel compounds, F3 -PLGA and F9 -PLGA, were synthesized and their chemical structure and thermal stability were analyzed by solution NMR, DSC, and TGA. The obtained F-PLGA compounds were proven to form in aqueous solution colloidal stable nanoparticles (NPs) displaying a strong 19 F NMR signal. The fluorinated NPs also showed an enhanced ability to load hydrophobic drugs containing fluorine atoms compared to analogous pristine PLGA NPs. Preliminary in vitro studies showed high cell viability and the NP ability to intracellularly deliver and release a functioning drug.