Paolo Ferruti

University of Milan | UNIMI · Department of Chemistry

Linear amphoteric polyamidoamines (PAAs) are usually water-soluble, biodegradable and biocompatible. Crosslinked PAAs form in water hydrogels, retaining most of the favorable properties of their linear counterparts. The hydrogels prepared by the radical post-polymerization of the oligo-α,ω-bisacrylamido-terminated PAA called AGMA1, obtained by the...

Polyamidoamines (PAAs) are biocompatible and biodegradable polymers with a huge potential as biomaterials for pharmaceutical applications. They are obtained by the step-wise aza-Michael polyaddition of bifunctional or multifunctional amines with bisacrylamides in water. To the best of our knowledge, no synthetic protocols leading to hyperbranched P...

Hydrophilic cyclodextrin nanosponges were prepared by the oxo-Michael polyaddition in an aqueous solution at pH > 10 of α-, β-, and γ-cyclodextrin with 1,4-bisacryloylpiperazine or 2,2-bisacrylamidoacetic acid. These nanosponges and, for comparison purposes, their precursor cyclodextrins were tested as sorbents of o-toluidine, a carcinogenic wastew...

The aza-Michael polyaddition of L-arginine and N,N′-methylene-bis-acrylamide gives the biocompatible and easily cell-internalized polyamidoamine ARGO7. By controlled synthesis, two ARGO7 oligomers, namely a trimer and a pentamer, bearing acrylamide terminal units, were obtained as precursors of the β-cyclodextrin-end-terminated oligomers P3 and P5,...

The eco-compatibility of the glycine-derived polyamidoamine M-GLY, chosen as the benchmark for water-soluble polyamidoamines, was investigated by means of the seed germination test using watercress seeds. The percent germinated seeds and their root elongation were measured, and the corresponding germination index (GI) calculated for each set of dat...

A linear polyamidoamine (PAA) named BAC-EDDS, containing metal chelating repeat units composed of two tert-amines and four carboxylic groups, has been prepared by the aza-Michael polyaddition of ethylendiaminodisuccinic (EDDS) with 2,2-bis(acrylamido)acetic acid (BAC). It was characterized by size exclusion chromatography (SEC), FTIR, UV–Vis and NM...

Linear polyamidoamines (PAAs) derived from the polyaddition of natural α-amino acids and N,N′-methylene bis(acrylamide) are intumescent flame retardants for cotton. Among them, the glycine-derived M-GLY extinguished the flame in horizontal flame spread tests at 4% by weight add-on. This paper reports on an extensive study aimed at understanding the...

In this paper, bioinspired polyamidoamines (PAAs) were synthesized from N,N0 -methylene bisacrylamide and nine natural α-amino acids: L-alanine, L-valine, L-leucine (M-LEU), L-histidine, L-serine, L-asparagine, L-glutamine (M-GLN), L-aspartic acid and L-glutamic acid (M-GLU) and their performance as flame retardants (FRs) for cotton were determined...

The hitherto known polyamidoamines (PAAs) are not suitable as structural materials because they are usually water-soluble or swellable in water. This paper deals with the synthesis and characterization of semi-crystalline hydrophobic PAAs (H-PAAs) by combining different bis-sec-amines with bis-acrylamides obtained from C6–C12 bis-prim-amines. H-PAA...

Strategies for endosomal escape and access to the cell nucleus are highly sought for nano-carriers to deliver their load efficiently following endocytosis. In this work, we have studied the uptake and intracellular trafficking of a polycationic polyamidoamine endowed with a luminescent Ru complex, Ru-PhenAN, that shows unique trafficking to the cel...

This paper aims at elucidating the degradation mechanism of linear polyamidoamines (PAAs) in water. PAAs are synthesized by the aza-Michael polyaddition of prim-monoamines or bis-sec-amines with bisacrylamides. Many PAAs are water-soluble and have potential for biotechnological applications and as flame-retardants. PAAs have long been known to degr...

D-and L-arginine-based polyamidoamino acids, called D-and L-ARGO7, retain the chirality and acid/base properties of the parent amino acids and show pH-dependent self-structuring in water. The ability of the ARGO7 chiral isomers to selectively interact with chiral biomolecules and/or surfaces was studied by choosing sodium deoxycholate (NaDC) as a m...

This paper reports on synthesis, acid-base properties, and self-structuring in water of a chiral polyamidoamino acid, M-L-Gln, obtained from the polyaddition of N,N'-methylenebisacrylamide with L-glutamine, with the potential of establishing hydrogen bonds through its prim-amide pendants. The M-L-Gln showed pH-responsive circular dichroism spectra,...

Gold nanoparticles are elective candidate for cancer therapy. Current efforts are devoted to developing innovative methods for their synthesis. Besides, understanding their interaction with cells have become increasingly important for their clinical application. This work aims to describe a simple approach for the synthesis of extra-small gold nano...

The polyamidoamine derived from N,N′-methylenebisacrylamide (M) and glycine (G), M-G, has been shown to be an effective flame-retardant (FR) for cotton in horizontal flame spread tests (HFST), extinguishing the flame at 5% add-on. Its activity was attributed to its intrinsic intumescence. In vertical flame spread tests (VFST), M-G failed to extingu...

In this work, we report the synthesis of [Ru(phen)32+]-based complexes and their use as photosensitizers for photodynamic therapy (PDT), a treatment of pathological conditions based on the photoactivation of bioactive compounds, which are not harmful in the absence of light irradiation. Of these complexes, Ru-PhenISA and Ru-PhenAN are polymer conju...

Linear polyamidoamines containing disulphide groups (SS-PAAs) were prepared by polyaddition of L-cystine with 2,2-bisacrylamidoacetic acid (B-CYSS), N,N′-methylenebisacrylamide (M-CYSS) and 1,4-bisacryloylpiperazine (BP-CYSS). They were evaluated as flame retardants for cotton, alone or with cellulose-derived nano-graphene oxide (nGO) carbon dots,...

Polyamidoamino acids (PAACs) are synthetic polymers prepared by the polyaddition of bisacrylamides with natural α-amino acids, which in the process maintain both their chirality and their amphoteric nature. This polymerization process is slow, but has the merits of taking place in water and of neither involving protection/de-protection steps nor re...

We present multifunctional, biocompatible and biodegradable magnetic nanovectors based on different polyamidoamine (PAA) polymers tailored with different diagnostic and therapeutic properties. Using maghemite nanoparticles with average size 15.5 ± 2.8 nm prepared by thermal decomposition, superparamagnetic nanovectors were obtained by coating the n...

The fate of macromolecules of biological or pharmacological interest that enter the mucus barrier is a current field of investigation. Studies of the interaction between the main constituent of mucus, mucins, and molecules involved in topical transmucoidal drug or gene delivery is a prerequisite for nanomedicine design. We studied the interaction o...

Chiral polyamidoamino acids were obtained by polyaddition of N,N'-methylenebisacrylamide with D-, D,L-and L-tryptophan (M-D-Trp, M-D,L-Trp and M-L-Trp). L-tryptophan/glycine copolymers, M-G-L-Trp 5 , M-G-L-Trp 10 , M-G-L-Trp 20 and M-G-L-Trp 40, were prepared from L-tryptophan/glycine mixtures. These polymers were amphoteric, with acid-base propert...

This paper reports on synthesis, acid-base properties and self-structuring in water of chiral polyamidoamino acids (PAACs) obtained by polyaddition of N,N-methylenebisacrylamide with L-alanine, L-valine and L-leucine (M-L-Ala, M-L-Val, M-L-Leu) with potential for selective interactions with biomolecules. The polymers maintained the acid-base proper...

Current strategies for the mass administration of antimalarial drugs demand oral formulations to target the asexual Plasmodium stages in the peripheral bloodstream, whereas recommendations for future interventions stress the importance of also targeting the transmission stages of the parasite as it passes between humans and mosquitoes. Orally admin...

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Bioinspired polyamidoamines containing disulfide-groups in the main chain (SS-PAAs), prepared by Michael polyaddition of 2,2-bis(acrylamido)acetic acid with l-cystine (B-CYSS) and of N,N′-bis(acryloyl- l-cystine) with either glycine or 2-methylpiperazine (BACYSS-GLY and BACYSS-MP), were investigated as intumescent surface-confined flame retardants...

Purpose: This study aimed to further explore the mechanisms behind the ability of certain linear polyamidoamines (PAAs) to transfect cells with minimal cytotoxicity. Methods: The transfection efficiency of DNA complexed with a PAA of a molecular weight over 10 kDa or 25 kDa branched polyethyleneimine (BPEI) was compared in A549 cells using a luc...

Eight linear polyamidoamines (PAAs) prepared by polyaddition of amines to bisacrylamides are investigated as intumescent surface-confined flame retardants for cotton textiles. The structure of the amine-derived subunits governs their performances. In ignitability tests, aminoacid-deriving PAAs exposed to direct flame for 10 s do not burn, but produ...

Photosensitizers belonging to the boron-dipyrromethenes (BODIPYs) class were recently found endowed with good efficacy in the antibacterial photodynamic therapy (aPDT) against both Gram-positive and Gram-negative bacteria. In this paper, we report on the remarkable adjuvant effect exerted in this respect by linear polyamidoamines (PAAs), a family o...

AGMA1, a prevailingly cationic, guanidine-bearing, linear, amphoteric polyamidoamine is an effective siRNA condensing agent. Here two AGMA1 samples of different molecular weight, i.e. AGMA1-5 and AGMA1-10 were evaluated as siRNA condensing agents and transfection promoters. AGMA1-10 formed stable polyplexes with a size lower than 50 nm and positive...

Glucocorticoids are widely prescribed in treatment of rheumatoid arthritis, asthma, systemic lupus erythematosus, lymphoid neoplasia, skin and eye inflammations. However, well-documented adverse effects offset their therapeutic advantages. In this work, novel nano-hydrogels for the sustained delivery of dexamethasone were designed to increase both...

The initial steps of viral infections are mediated by interactions between viral proteins and cellular receptors. Blocking the latter with high-affinity ligands may inhibit infection. DC-SIGN, a C-type lectin receptor expressed by immature dendritic cells and macrophages, mediates human immunodeficiency virus (HIV) infection by recognizing mannose...

Electrospun poly-l-lactic acid (PLLA) nanofiber mats carrying surface amine groups, previously introduced by nitrogen atmospheric pressure nonequilibrium plasma, are embedded into aqueous solutions of oligomeric acrylamide-end capped AGMA1, a biocompatible polyamidoamine with arg-gly-asp (RGD)-reminiscent repeating units. The resultant mixture is f...

This paper reports on the development of montmorillonite (MMT) – reinforced hydrogels based on a peptidomimetic polyamidoamine carrying guanidine pendants (AGMA1), as substrates for the osteoinduction of osteoblast precursor cells. AGMA1 hydrogels of various crosslinking degrees responded favourably to MMT reinforcement, giving rise to composite hy...

The radical polymerization of 1-vinylpyrrolidin-2-one (NVP) in poly(lactic-co-glycolic acid) (PLGA) 50:50 at 100 °C leads to amphiphilic PLGA-g-PVP copolymers. Their composition is determined by FT-IR spectroscopy. Thermogravimetric analyses agree with FT-IR determinations. Saponification of the PLGA-g-PVP polyester portion allows isolating the PVP...

The development of topical microbicides is a valid approach to protect the genital mucosa from sexually transmitted infections that cannot be contained with effective vaccination, like HSV and HIV infections. A suitable target of microbicides is the interaction between viral proteins and cell surface heparan sulfate proteoglycans (HSPGs). AGMA1 is...

4-hydroxynonenal (HNE), a lipid peroxidation product, is a promising anti-neoplastic drug due to its remarkable anti-cancer activities. However, this possibility has not been explored, because the delivery of HNE is very challenging as a result of its low solubility and its poor stability. This study intentionally designed a new type of lipid nanoc...

The agmatine-containing poly(amidoamine) polymer AGMA1 was recently shown to inhibit the infectivity of several viruses, including human papillomavirus type 16 (HPV-16), that exploit cell surface heparan sulfate proteoglycans (HSPGs) as attachment receptors. The aim of this work was to assess the antiviral activity of AGMA1 and its spectrum of acti...

In the rapidly evolving field of tissue engineering, continuous advances are required to improve scaffold design and fabrication to obtain biomimetic supports for cell adhesion, proliferation, penetration and differentiation. Both electrospun fibrous scaffolds and hydrogels are widely used in this field since they well reproduce the structure of th...

A polymer complex (1P) was synthesized by binding bis(cyclometalated) Ir(ppy)2(+) fragments (ppy = 2-phenylpyridyl) to phenanthroline (phen) pendants of a poly(amidoamine) copolymer (PhenISA, in which the phen pendants involved ∼6% of the repeating units). The corresponding molecular complex [Ir(ppy)2(bap)](+) (1M, bap = 4-(butyl-4-amino)-1,10-phen...

This paper reports on a novel application of an amphoteric water-soluble polyamidoamine named AGMA1 bearing 4-butylguanidine pendants. AGMA1 is an amphoteric, prevailingly cationic polyelectrolyte with isoelectric point of about 10. At pH 7.4 it is zwitterionic with an average of 0.55 excess positive charges per unit, notwithstanding it is highly b...

Poly(amidoamine)s (PAAs) are multifunctional tert-amine polymers endowed with high structural versatility. Here we report on the screening of a minilibrary of PAAs against a panel of viruses. The PAA AGMA1 showed antiviral activity against herpes simplex virus, human cytomegalovirus, human papillomavirus 16, and respiratory syncytial virus but not...

A linear amphoteric poly(amidoamino acid), L-ARGO7, is prepared by Michael-type polyaddition of L-arginine with N,N'-methylenebisacrylamide. Chain-extension of acrylamide end-capped L-ARGO7 oligomers with piperazine leads to high-molecular-weight copolymers in which L-arginine maintains its absolute configuration. Acid/base properties of L-ARGO7 po...

Current malaria therapeutics demands strategies able to selectively deliver drugs to Plasmodium-infected red blood cells (pRBCs) in order to limit the appearance of parasite resistance. Here, the poly(amidoamines) AGMA1 and ISA23 have been explored for the delivery of antimalarial drugs to pRBCs. AGMA1 has antimalarial activity per se as shown by i...

Malaria transmission-blocking (T-B) interventions are essential for malaria elimination. Small molecules that inhibit the Plasmodium ookinete-to-oocyst transition in the midgut of Anopheles mosquitoes, thereby blocking sporogony, represent one approach to achieving this goal. Chondroitin sulfate glycosaminoglycans (CS-GAGs) on the Anopheles gambiae...

Three-component nanocomposites, constituted by a superparamagnetic iron oxide core coated with a polymeric surfactant bearing tightly bound Re(CO)3 moieties, were prepared and fully characterized. The water soluble and biocompatible surfactant was a linear poly(amidoamine) copolymer (PAA), containing cysteamine pendants in the minority part (ISA23S...

4-Hydroxynonenal (HNE) is the most studied end product of the lipoperoxidation process, by virtue of its relevant biological activity. The anti-proliferative and pro-apoptotic effects of HNE have been widely demonstrated in a great variety of tumour cells types in vitro. Thus, it might represent a promising new molecule on strategies in anticancer...

Poly(amidoamine)s (PAAs) are a family of synthetic polymers obtained by stepwise polyaddition of prim- or sec-amines to bisacrylamides. Nearly all conceivable bisacrylamides and prim- or sec-amines can be employed as monomers endowing PAAs of a structural versatility nearly unique among stepwise polyaddition polymers. PAAs are degradable in aqueous...

A series of nanoparticles is prepared via layer-by-layer assembly of oppositely charged, synthetic biocompatible polyamidoamine polymers as potential carriers. Particle size, surface charge and internal chain mobility are quantified as a function of the polymer type and number of layers. The effect of addition of surfactant is examined to simulate...

This paper reports on the synthesis and physico-chemical, mechanical, and biological characterization of two sets of poly(amidoamine) (PAA) hydrogels with potential as scaffolds for in vivo peripheral nerve regeneration. They are obtained by polyaddition of piperazine with N,N'-methylenebis(acrylamide) or 1,4-bis(acryloyl)piperazine with 1,2-diamin...

INTRODUCTION Polyamidoamines (PAA)-based resins have recently emerged as an advantageous tool for metal ion pollutant sorption in water treatments, complying with nearly all desirable requirements for this application, such as bio-and eco-compatibility, effectiveness in aqueous systems, low cost and easy scaling up of preparation, biodegradability,...

Hyperbranched, water-soluble polymers, obtainable by Michael polyaddition of α-, β-, or γ-cyclodextrins and amines to bisacrylamides.

Autologous nerve grafting is considered the gold standard for bridging nerve lesion, although in several cases the use of artificial tubular guides is needed. Nowadays, the research is addressed to identify the ideal treatment able to support complete nerve regeneration and functional recovery. Therefore, the use of artificial synthetic or natural...

The activity of antivirals can be enhanced by their incorporation in nanoparticulate delivery systems. Peculiar polymeric nanoparticles, based on a β-cyclodextrin-poly(4-acryloylmorpholine) monoconjugate (β-CD-PACM), are proposed as acyclovir carriers. The experimental procedure necessary to obtain the acyclovir-loaded nanoparticles using the solve...

Traditional precipitation methods for inorganic micropollutant removal from waters are increasingly being replaced by sorption methods based on both natural and synthetic materials. In this context, two novel effective heavy metal ions absorbers are presented. These resins, LYMA and LMT85, were crosslinked poly(amidoamine)s carrying amine and carbo...

This article reports on a simple and straightforward preparation method of poly(amidoamine)s (PAAs) with hetero-difunctional chain ends as well as of several up to now hardly obtainable PAA derivatives of biotechnological interest, such as for instance PAAs of controlled molecular weight and narrow polydispersity mono-functionalized at one end with...

A new amphoteric copolymer, PhenISA, has been obtained by copolymerization of 4-(4'-aminobutyl)-1,10-phenanthroline (BAP) with 2-methylpiperazine and bis(acrylamido)acetic acid (BAC) (6% of phenanthroline-containing repeating units). The copolymer showed excellent solubility in water, where it self-aggregated to give clear nanoparticle suspensions...

In this study, the gene delivery properties of new hyperbranched poly(amido amine)s (PAAs) with disulfide linkages in the main chain were investigated in comparison with their linear analogs. Eight different bioreducible PAAs were prepared by Michael addition of N,N'-bisacryloylpiperazine (BP) with cystamine (CYST) or N,N'-dimethylcystamine (DMC) a...

Structure and Preparation Polyamidoamines (PAAs) are synthetic polymers carrying amide-(a) and tert-amine (b) groups regularly arranged along the polymer chain according to the sequences …a…a…b…b… or …a…a…b…. They are prepared by Michael polyaddition of primary or secondary amines to bisacrylamides (Scheme 1) (Danusso and Ferruti, 1970; Ferruti, 19...

Polymer-drug and polymer-protein conjugates are emerging as a robust and well-characterized class of therapeutic entity. Although there are no low-molecular-weight soluble polymer conjugates in routine clinical use, there are many examples of routinely used high-molecular-weight drugs conjugated to soluble polymers (e.g., Oncospar). Advances in syn...

Polyamidoamines (PAAs) are a well-known family of synthetic biocompatible and biodegradable polymers, which can be prepared as soft hydrogels characterized by low interfacial tension and tunable elasticity. For the first time we report here on the in vivo performance of a PAA hydrogel implant as scaffold for tissue engineering. In particular, an am...

The “swelling–poling–deswelling” technique is a new procedure of poling crosslinked polymeric network carrying covalently attached NLO (nonlinear optical) chromophores. It is based upon a solvent-swollen crosslinked polymeric network before submission to poling. Under electrical poling, the matrix is deswelled without heating above the polymer Tg (...

Biodegradable and biocompatible poly(amidoamine)-(PAA-) based hydrogels have been considered for different tissue engineering applications. First-generation AGMA1 hydrogels, amphoteric but prevailing cationic hydrogels containing carboxylic and guanidine groups as side substituents, show satisfactory results in terms of adhesion and proliferation p...