Biocompatible Preparation of Beta-Lactoglobulin/Chondroitin Sulfate Carrier Nanoparticles and Modification of Their Colloidal and Hydropathic Properties by Tween 80.

The electrostatic complexation of the protein beta-lactoglobulin (ß-LG) with the anionic polysaccharide chondroitin sulfate (CS) and the subsequent stabilization by thermal treatment were studied to achieve the well-defined nanoparticles (NPs). The formation of the well-defined NPs was obtained at pH 4 with a hydrodynamic radius from 60 to 80 nm. NP aggregation was observed at pH 1.5 because of the loss of the anionic charge of chondroitin sulfate on the surface of the NPs. After thermal treatment, the NPs exhibited stability against a pH increase to pH 7 while a stronger aggregation at pH 1.5 was observed. Core-shell structures were found at pH 7 after thermal treatment, indicating a possible mechanism of partial disintegration. The addition of Tween 80 (T80) before thermal treatment led to the formation of T80 self-assemblies inside the NPs. This caused an increase in the hydrophobicity of the inner and outer surfaces of the NPs as it was observed by fluorescence spectroscopy. The ζ-potential of the complexes and NPs was about -20 mV while the presence of T80 did not affect it. FTIR spectra verified changes of the secondary structure of ß-LG in its complexes with CS and T80. The thermally treated NPs exhibited high surface and overall hydrophobicity and stability in high salinity and biocompatible solutions. The thermally treated NPs showed colloidal and physicochemical stability for 1 month, which were enhanced by the addition of T80. Due to the nature of the precursors and their colloidal properties, the NPs are highly promising for applications as biocompatible drug delivery nanocarriers while T80 acts as an agent to modify their properties.

An investigation of a strengthening polysaccharide interfacial membrane strategy utilizing an anionic polysaccharide-alkaline ligand interfacial assembly for all-liquid printing.

The applications of polysaccharides as emulsifiers are limited due to the lack of hydrophobicity. However, traditional hydrophobic modification methods used for polysaccharides are complicated and involve significant mechanical and thermal losses. In this study, soy hull polysaccharide (SHP) and terminally aminopropylated polydimethylsiloxane (NPN) were selected to investigate the feasibility of a simple and green interfacial membrane strengthening strategy based on the interfacial polymerization of anionic polysaccharides and fat-soluble alkaline ligands. Our results show that deprotonated SHP and protonated NPN can be complexed at the water/oil (W/O) interface, reduce interfacial tension, and form a strong membrane structure. Moreover, they can quickly form a membrane at the W/O interface upon the moment of contact to produce stable all-liquid printing products with complex patterns. However, the molecular weight of NPN affects the complexation reaction. Consequently, this study has long-term implications to expanding the areas of application for anionic polysaccharides.

Lactoferrin thermal stabilization and iron(II) fortification through ternary complex fabrication with succinylated sodium caseinate.

A thermally stable co-delivery system for lactoferrin (LF) and iron(II) was developed to address iron deficiency anemia. Complexes were formed between LF, succinylated sodium caseinate (S.NaCas) and FeSO4 with high yield (∼85%). LF-S.NaCas-Fe complexes achieved loading capacities for iron(II) between 2.5 and 12 mg g-1and LF loading capacities between 250 and 690 mg g-1, depending upon initial Fe2+ concentrations and LF ratios. The LF-S.NaCas complex mixtures appeared as smooth cubic particles in SEM, and gradually aggregated to amorphous particles as th iron(II) concentration increased due to iron-facilitated cross-linking. The complexation significantly improved LF thermal stability and addressed the poor solubility of iron(II) under neutral pH. After thermal treatment (95 °C, 5 min), the rehydrated complexes retained 68%-90% LF, with <10% iron(II) release. Circular dichroism spectra showed the secondary structure of the complexed LF was well retained during thermal treatment. This thermally stable system showed great potential in LF thermal protection and iron(II) fortification.

Combining and concentrating nanocelluloses for cryogels with remarkable strength and wet resilience.

Cellulose cryogels are promising eco-friendly materials that exhibit low density, high porosity, and renewability. However, the applications of these materials are limited by their lower mechanical and water resistance compared to petrochemical-based lightweight materials. In this work, nanocelluloses were functionalized with cationic and anionic groups, and these nanomaterials were combined to obtain strong and water-resilient cryogels. To prepare the cryogels, anionic and cationic micro- and nanofibrils (CNFs) were produced at three different sizes and combined in various weight ratios, forming electrostatic complexes. The complex phase was concentrated by centrifugation and freeze-dried. Porous and open cellular structures were assembled in all compositions tested (porosity >90 %). Compressive testing revealed that the most resistant cryogels (1.7 MPa) were obtained with equivalent amounts of negatively and positively charged CNFs with lengths between 100 and 1200 nm. The strength at this condition was achieved as CNF electrostatic complexes assembled in thick cells, as observed by synchrotron X-ray tomography. In addition to mechanical strength, electrostatic complexation provided remarkable structural stability in water for the CNF cryogels, without compromising their biodegradability. This route by electrostatic complexation is a practical strategy to combine and concentrate nanocelluloses to tailor biodegradable lightweight materials with high strength and wet stability.

New approaches for modulation of alginate-chitosan delivery properties.

Alginate is a biopolymer widely used on delivery systems when bioactive protection at acidic pH is required, while chitosan can enhance mucoadhesion and controlled release at alkaline pHs. In this work, alginate ionotropic gelation and electrostatic complexation to chitosan were evaluated concomitantly or in a two-step approach to improve the delivery properties of systems in different pHs. The effect of pH on alginate gelation and chitosan interactions were also evaluated. Alginate microspheres were prepared by ionotropic gelation in CaCl2 at different pH values (2.5 and 6.0) by extrusion. Complexation with chitosan was carried out during alginate ionotropic gelation (one-step approach) or after alginate gel formation (two-step approach). Alginate microparticles without chitosan showed larger pores and lower mechanical strength. Extruded microspheres at pH 6.0 were more stable to pH and showed smaller pores than the formed at pH 2.5. One-step production retained a large amount of bioactive at pH 7.0 and resulted in lower release at the pH of intestinal digestion. The two-step approach retained less amount of bioactive but confer more protection to the pH of the stomach phase and higher release in pH of the intestinal phase than one-step samples. These results indicate that the formation of alginate gels by ionotropic gelation followed by the complexation with chitosan (in two-step) is promising for the transport and delivery of bioactives into intestinal conditions, whereas the ionotropic gelation concomitantly to electrostatic complexation (one-step approach) is indicated to the delivery of bioactives into lower pH environments.

Thermally stabilized chondroitin sulfate-hemoglobin nanoparticles and their interaction with bioactive compounds.

The preparation of nanoparticles (NPs) based on hemoglobin (Hb) with a fully biocompatible methodology is presented. The spontaneous formation of electrostatic complexes of Hb with chondroitin sulfate (CS) at pH 4 in the polysaccharide/protein mass ratio regime where charge neutrality is met leads to spherical nanostructures with monomodal hydrodynamic radii distribution in the range of 50-100 nm. The integrity of the electrostatic complexes is disturbed at pH 7 as the net electric charge of Hb is very low. Treating the NPs at mildly elevated temperature stabilizes them against the pH increase taking advantage of Hb's ability of unfolding and self-associating upon thermal treatment. The NPs surface charge is pH-tunable and changes from positive to strongly negative upon pH increase to 7 proving the presence of negative surface patches of Hb and CS segments in their exterior. The α-helix content of Hb does not change significantly by thermal treatment. The NPs are found to bind the bioactive compounds curcumin and ß-carotene and are stable in solutions with high salt content. This investigation introduces a straightforward method to formulate Hb in NPs with possibilities in the nanodelivery of nutrients and drugs.

Adsorption of Preformed Microgel-Enzyme Complexes as a Novel Strategy toward Engineering Microgel-Based Enzymatic Biosensors.

A novel approach to surface modification, which consists of the adsorption of microgel-enzyme complexes preformed in solution, is highlighted. Accordingly, the microgel-enzyme complexes were formed due to the electrostatic interaction of the oppositely charged interacting components, that is, a cationic poly(N-isopropylacrylamide)-based microgel and glucose oxidase taken as a model enzyme. The spontaneous adsorption of the prepared microgel-enzyme complexes, examined by means of quartz crystal microbalance with dissipation monitoring and atomic force microscopy, was observed, resulting in the formation of well-adhered microgel-enzyme coatings. Further, the preformed microgel-enzyme complexes were adsorbed onto the modified graphite-based screen-printed electrodes, and their enzymatic responses were determined by means of amperometry, demonstrating a remarkable analytical performance toward the quantification of ß-D-glucose in terms of high sensitivity (0.0162 A × M-1 × cm-2), a low limit of detection (1 µM), and an expanded linear range (1-2000 µM). The fabricated microgel-enzyme biosensor constructs were found to be very stable against manifold-repeated measurements. Finally, the pH- or salt-induced release of glucose oxidase from the adsorbed preformed microgel-enzyme complexes was demonstrated. The findings obtained for the microgel-enzyme coatings prepared via adsorption of the preformed microgel-enzyme complexes were compared to those found for the microgel-enzyme coatings fabricated via a previously exploited two-stage sequential adsorption, which includes the adsorption of the microgel first, followed by the electrostatic binding of glucose oxidase by the adsorbed microgel.

Self-assembled chitosan-insulin oral nanoparticles - A critical perspective review.

Chitosan is an abundant natural cationic polysaccharide with excellent biodegradability, bioadhesion, and biocompatibility. Chitosan is extensively researched for various particulate oral insulin drug delivery systems. Oral insulin is economically efficient and more convenient than injections, with greater patient compliance. Electrostatic ionic interaction between cationic chitosan and anionic polymer or insulin leads to the formation of spontaneously self-assembled nanoparticles. This simple technique attracted many researchers as it can be carried out quickly in mild conditions without harmful solvents, such as surfactants or chemical cross-linkers that might degrade the insulin structure. The formulated chitosan nanoparticles help to protect the core insulin from enzymatic degradation in the digestive system and improve paracellular intestinal uptake from the enterocytes due to mucoadhesion and reversible tight junction opening. Moreover, functionalized chitosan nanoparticles create newer avenues for targeted and prolonged delivery. This review focuses on modified chitosan-insulin nanoparticles and their implications on oral insulin delivery. Dependent variables and their optimal concentration ranges used in self-assembly techniques for chitosan-insulin nanoparticular synthesis are summarized. This review provides a comprehensive guide to fine-tune the essential factors to formulate stable insulin-chitosan nanoparticles using mild ionic interactions.

N,N,N-Trimethyl chitosan as a permeation enhancer for inhalation drug delivery: Interaction with a model pulmonary surfactant.

N,N,N-Trimethyl chitosan (TMC), a biocompatible and biodegradable derivative of chitosan, is currently used as a permeation enhancer to increase the translocation of drugs to the bloodstream in the lungs. This article discusses the effect of TMC on a mimetic pulmonary surfactant, Curosurf®, a low-viscosity lipid formulation administered to preterm infants with acute respiratory distress syndrome. Curosurf® exhibits a strong interaction with TMC, resulting in the formation of aggregates at electrostatic charge stoichiometry. At nanoscale, Curosurf® undergoes a profound reorganization of its lipid vesicles in terms of size and lamellarity. The initial micron-sized vesicles (average size 4.8 µm) give way to a froth-like network of unilamellar vesicles about 300 nm in size. Under such conditions, neutralization of the cationic charges by pulmonary surfactant may inhibit TMC permeation enhancer capacity, especially as electrostatic charge complexation is found at low TMC content. The permeation properties of pulmonary surfactant-neutralized TMC should then be evaluated for its applicability as a permeation enhancer for inhalation in the alveolar region.

Conformation changes and emulsifying properties of myofibrillar proteins in water: Effects of electrostatic interaction with chitosan.

Great interests have been attracted toward muscle protein in a water-soluble state with improved functionality for further designing meat protein fortified low-salt functional foods. In the present study, electrostatic interaction of chitosan (CH) with myofibrillar proteins (MP) in water aqueous solution was investigated, and the linked structure changes and emulsion stabilization of MP were studied. Results showed that the electrostatic interaction inhibited MP aggregation, and smaller particle size complexes were formed at pH 6.0, leading to the loss of ß-sheet contents and recovery of α-helix contents with decreasing MP/CH mixing ratio (5:1 and 1:1). The tertiary structure confirmed the conformation changes of MP in which more hydrophobic groups and active sulfhydryl groups were exposed (P < 0.05), and the fluorescence was also quenched. With decreasing mixing ratio, the droplet size of emulsion decreased (P < 0.05), while the absorbed protein content increased (P < 0.05). After 7 d of storage, complex at a ratio of 1:1 displayed desirable emulsion stability, which could be due to the improved emulsifying capacity, enhanced electrostatic repulsion and steric effects. These findings provide a better understanding of conformation changes of MP in water aqueous solution induced by electrostatic interactions at mild acidic pH and help to fabricate stable protein/polysaccharide emulsification systems for further developing meat protein-based functional food to deliver health.

Hydrogen Peroxide-Activated Nitric Oxide-Releasing Vancomycin-Loaded Electrostatic Complexation for Efficient Elimination of Methicillin-Resistant Staphylococcus aureus Abscesses.

The treatment of subcutaneous abscesses has been greatly hindered due to the spread of drug-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA). Thus, alternative strategies are highly desired to complement conventional antibiotic therapies and surgical intervention. As one of such strategies, applications of nitric oxide (NO) have shown great potential in the treatment of bacteria-induced subcutaneous abscesses by improving the efficacy of many therapeutic methods. However, it is extremely challenging to achieve precise delivery and controlled release because of its gaseous nature. In the present study, an effective strategy was reported in which on demand hydrogen peroxide (H2O2)-activated nitric oxide-releasing vancomycin (Van)-loaded electrostatic complexation (Lipo/Van@Arg) was fabricated. In this system, Van was encapsulated into a negative-charged DSPG/Chol liposome (Lipo/Van) and electrostatically bound with the positive-charged l-arginine (l-Arg). As expected, Lipo/Van@Arg exhibited superior bacterial binding and biofilm penetration abilities. After being in the interior of the biofilms, Lipo/Van@Arg could be triggered by the endogenous H2O2 and effectively release NO. The released NO could exhibit combined antibacterial and biofilm eradication effects with Van. Moreover, an in vivo evaluation using a BALB/c mouse model of subcutaneous abscesses indicated that the combination treatment of NO and Van based on Lipo/Van@Arg could effectively eliminate MRSA from the abscesses, thereby preventing abscess recurrence. In summary, the Lipo/Van@Arg system developed in this study realized controlled delivery and precise release of NO, which had significant clinical implications in the efficient treatment of abscesses.

Protein-polysaccharide interactions for the fabrication of bioactive-loaded nanocarriers: Chemical conjugates and physical complexes.

As unique biopolymeric architectures, covalently and electrostatically protein-polysaccharide (PRO-POL) systems can be utilized for bioactive delivery by virtue of their featured structures and unique physicochemical attributes. PRO-POL systems (i. e, microscopic /nano-dimensional multipolymer particles, molecularly conjugated vehicles, hydrogels/nanogels/oleogels/emulgels, biofunctional films, multilayer emulsion-based delivery systems, particles for Pickering emulsions, and multilayer coated liposomal nanocarriers) possess a number of outstanding attributes, like biocompatibility, biodegradability, and bioavailability with low toxicity that qualify them as powerful agents for the delivery of different bioactive ingredients. To take benefits from these systems, an in-depth understanding of the chemical conjugates and physical complexes of the PRO-POL systems is crucial. In this review, we offer a comprehensive study concerning the unique properties of covalently/electrostatically PRO-POL systems and introduce emerging platforms to fabricate relevant nanocarriers for encapsulation of bioactive components along with a subsequent sustained/controlled release.

On-Demand Multifunctional Electrostatic Complexation for Synergistic Eradication of MRSA Biofilms.

Recently, methicillin-resistant Staphylococcus aureus (MRSA) severely threatened the public health, especially when the biofilms developed. Although the biofilm eradication capability of nanoparticles (NPs) has been proposed and confirmed, efficient biofilm penetration and retention are still a big challenge. To solve this problem, a multifunctional electrostatic complexation (denoted as TDZ-G4@CA) was constructed for biofilm combination therapy. TDZ-G4@CA was composed of a TDZ-grafted amino-ended poly(amidoamine) dendrimer (TDZ-PAMAM) as the inner core and cis-aconitic anhydride-modified d-tyrosine (CA-Tyr) wrapped outside via electrostatic interaction. In our design, TDZ-G4@CA could simultaneously reduce the particle size and reverse the surface charge under an acidic microenvironment, which was designed for efficient biofilm penetration and retention. Meanwhile, the on-demand two-step sequential delivery of biofilm dispersal and antibacterial agents was also obtained. The acid responsiveness of TDZ-G4@CA triggered the immediate release of d-Tyr to damage the matrix of the biofilm. Subsequently, TDZ-G4 could penetrate over the depth of the biofilm and bind tightly to MRSA, which could enhance the permeability of the bacterial membrane for TDZ internalization. Additionally, TDZ exhibited a sustained-release pattern as a response to lipase to maintain an effective bactericidal concentration for a long time. As expected, in vitro experiments demonstrated that surface charge/particle size-adaptive TDZ-G4@CA with a sequential delivery strategy exhibited intensive infiltration in the biofilm matrix and excellent biofilm eradication capabilities. Afterward, in vivo experimental results also confirmed the prolonged circulation time and comprehensive therapeutic efficacy of TDZ-G4@CA against MRSA-induced subcutaneous abscess without any systemic side effects. Based on the comprehensive evaluation of the therapeutic outcome, the electrostatic complexation (TDZ-G4@CA) can serve as a promising strategy for enhanced antibiotic therapy for combating biofilm-associated infections.

Preparation and characterization of octenyl succinic anhydride modified waxy maize starch hydrolyzate/chitosan complexes with enhanced interfacial properties.

The preparation and characterization of colloidal complexes based on octenyl succinic anhydride starch hydrolyzate (OSAS) and chitosan (CS) were conducted. Results showed that OSA-S/CS ratio (r) and pH significantly affected complex turbidities and yields. The highest turbidity and yield were obtained at r = 6:1 when pH was fixed, and at pH 6.5 when r was fixed. All complexes remained liquid-like except that formed at pH 6.5, which exhibited a gel structure due to the strongest complexation. OSA-S/CS complexes had intertwined core-shell microstructure and exhibited electrostatic interactions between COO- and NH3+ groups of OSA-S and CS, respectively. The complexes prepared at r = 6:1 and pH 6.0 exhibited the most suitable wettability (θow = 91.97°) and interfacial adsorption dynamics. The compact lamellar network and intact cores of these complexes were also shown. This work provides profound and comprehensive information about the formation and physicochemical properties of OSA-S/CS complexes.

Gelatin-loaded cubosomes stabilized with hydrophobically modified quaternized cellulose nanofiber and their pH-dependent release property.

Monoolein cubic phase immobilizing hydrophobically modified gelatin (HmGel) in its water channel was prepared by a melt-hydration method. The cubic phase was micronized into cubosomes by using hydrophobically modified quaternized cellulose nanofiber (HmQCNF) as a stabilizer. The phase transition temperature of the cubic phase was about 68-70 °C. Small angle X-ray diffraction revealed that HmGel-loaded cubosome stabilized with HmCNF was a diamond type of cubic phase. HmGel-loaded cubosomes stailized with HmQCNF were dependent on the pH value in terms of the release of their payload (i.e, methylene blue) much more strongly than HmGel-loaded cubosomes stabilized with Pluronic F127.

Tailoring strength of nanocellulose foams by electrostatic complexation.

Supramolecular assembly of biobased components in water is a promising strategy to construct advanced materials. Herein, electrostatic complexation was used to prepare wet-resilient foams with improved mechanical property. Small-angle X-ray scattering and cryo-transmission electron microscopy experiments showed that suspensions with oppositely charged cellulose nanofibers are a mixture of clusters and networks of entangled fibers. The balance between these structures governs the colloidal stability and the rheological behavior of CNFs in water. Foams prepared from suspensions exhibited maximum compressive modulus at the mass composition of 1:1 (ca 0.12 MPa), suggesting that meaningful attractive interactions happen at this point and act as stiffening structure in the material. Besides the electrostatic attraction, hydrogen bonds and hydrophobic contacts may also occur within the clustering, improving the water stability of cationic foams. These results may provide a basis for the development of robust all- cellulose materials prepared in water, with nontoxic chemicals.

Nanocellulose-lysozyme colloidal gels via electrostatic complexation.

Biohybrid colloids were fabricated based on electrostatic complexation between anionic TEMPO-oxidized cellulose nanofibrils (TO-CNF) and cationic hen egg white lysozyme (HEWL). By altering the loading of HEWL, physical colloidal complexes can be obtained at a relatively low concentration of TO-CNF (0.1 wt%). At neutral pH, increasing the HEWL loading induces an increase in charge screening, as probed by zeta-potential, resulting in enhanced TO-CNF aggregation and colloidal gel formation. Systematic rheological testing shows that mechanical reinforcement of the prepared biohybrid gels is easily achieved by increasing the loading of HEWL. However, due to the relatively weak nature of electrostatic complexation, the formed colloidal gels exhibit partial destruction when subjected to cyclic shear stresses. Still, they resist thermo-cycling up to 90 °C. Finally, the pH responsiveness of the colloidal complex gels was demonstrated by adjusting pH to above and below the isoelectric point of HEWL, representing a facile mechanism to tune the gelation of TO-CNF/HEWL complexes. This work highlights the potential of using electrostatic complexation between HEWL and TO-CNF to form hybrid colloids, and demonstrates the tunability of the colloidal morphology and rheology by adjusting the ratio between the two components and the pH.

Field pea protein isolate/chitosan complex coacervates: Formation and characterization.

Influence of chitosan (Ch) with low, medium, and high molecular weight (LMW, MMW, and HMW) on the formation of field pea protein isolate (FPPI)/Ch complex coacervates was investigated. An increase in maximum turbidity and a gradual shift of critical pH values towards the isoelectronic point of FPPI were observed as the FPPI/Ch ratio increased. Formation of FPPI/Ch complex coacervates was dominated by the electrostatic and hydrophobic interactions. FPPI/Ch complex coacervates exhibited a porous network microstructure and relatively uniform-sized and even-distributed pores were found in FPPI/Ch-HMW coacervates. Different thermodynamic profiles were observed during complex coacervation between FPPI and Ch with varying MWs and the largest binding stoichiometry was observed in the Ch-MMW at pH 6.6. In summary, the Ch-HMW was demonstrated to be most suitable for the formation of FPPI/Ch complex coacervates with homogenous microstructure but caused less changes in the tertiary conformation of FPPI compared to the Ch-LWM and Ch-MMW.

Electrostatic complexation of ß-lactoglobulin aggregates with κ-carrageenan and the resulting emulsifying and foaming properties.

The electrostatic complexation of protein and polysaccharide and the functional properties of the complexes are significantly affected by the structure of protein aggregates and are important in the development of new food ingredients. In this work, natural globular ß-lactoglobulin (NGBLG), ß-lactoglobulin nanoparticles (BLGNP), and ß-lactoglobulin fibrils (BLGF) were prepared and complexed with κ-carrageenan (κ-car). Phase diagrams of the NGBLG-, BLGNP-, and BLGF-κ-car systems were established and divided into 4 regions: mixed soluble polymers (I), intramolecular soluble complex (II), intermolecular soluble complex (III), and intermolecular insoluble complex (IV). Aggregation shifted the boundaries of regions III and IV of BLGF- or BLGNP-κ-car to lower pH and higher protein aggregates/κ-car weight ratio (r), especially for BLGF-κ-car. The emulsifying and foaming properties of the 3 mixed systems were investigated in regions I and II. Complexes in region II had significantly better emulsifying properties than the corresponding mixtures in region I and the pure protein aggregates. Interestingly, phase separation resulted in different effects on the foaming properties of the 3 BLG-κ-car complexes, in which BLGF-κ-car complexation in region II decreased the foaming properties in region I but the complexation of NGBLG-κ-car and BLGNP-κ-car in region II increased the foaming properties. The BLGF-κ-car complex in regions I and II provided the best emulsifying and foaming properties. Interfacial data both on oil-water and air-water interfaces overall explained the emulsifying and foaming properties of the complexes.

Auto-degradable and biocompatible superparamagnetic iron oxide nanoparticles/polypeptides colloidal polyion complexes with high density of magnetic material.

HYPOTHESIS: Superparamagnetic iron oxide nanoparticles (SPIONs) are extensively used as building block of colloidal nanocomposites for biomedical applications. Strategies employed to embed them in a biodegradable and biocompatible polymer matrix often fail to achieve a high density of loading which would greatly benefit to applications such as imaging and hyperthermia. In this study, poly(acrylic acid) coated SPION (γ-Fe2O3-PAA) are self-assembled with hydrolysable poly(serine ester) by electrostatic complexation, leading to perfectly defined spherical particles with ultra-high density of magnetic material and an ability to auto-degrade into individual SPION and biocompatible byproducts. EXPERIMENTS: Self-assembly and auto-degradation of γ-Fe2O3-PAA/poly(serine ester) and γ-Fe2O3-PAA/poly(serine ester)-b-PEG colloidal particles are studied by light scattering and microscopy. Colloidal stability in bio-fluids, hyperthermia under alternating magnetic field, cellular uptake, cytotoxicity and degradation of γ-Fe2O3-PAA/poly(serine ester)-b-PEG in living cells are investigated. FINDINGS: A remarkably slow electrostatic complexation leads to dense superparamagnetic γ-Fe2O3-PAA/poly(serine ester)-b-PEG polyion complexes (PICs) with controlled sizes (150-500 nm) and times of degradation in aqueous solvents (700-5000 h). The material shows good sustainability during hyperthermia, is well taken up by MC3T3 cells and non-cytotoxic. TEM images reveal a mechanism of degradation by "peeling" and fragmentation. In cells, PICs are reduced into individual SPIONs within 72 h.