Search Results (113)

Background: Hydrogels are 3D networks of hydrophilic polymers with various biomedical applications, including tissue regeneration, wound healing, and localized drug delivery. Hydrogel conjugation links therapeutic agents to a hydrogel network, creating a delivery system with adjustable and flexible hydrogel properties and drug activity, allowing for controlled release and enhanced drug stability. Conjugating therapeutic agents to hydrogels provides innovative delivery formats, including injectable and sprayable dosage forms, which facilitate localized and long-lasting delivery. This approach enables non-viral therapeutic methods, such as insertional mutagenesis, and minimally invasive drug administration. Scope and Objectives: While numerous reviews have analyzed advancements in hydrogel synthesis, characterization, properties, and hydrogels as a drug delivery vehicle, this review focuses on hydrogel conjugation, which enables the precise functionalization of hydrogels with small molecules and macromolecules. Subsequently, a description and discussion of several bio-conjugated hydrogel systems, as well as binding motifs (e.g., “click” chemistry, functional group coupling, enzymatic ligation, etc.) and their potential for clinical translation, are provided. In addition, the integration of therapeutic agents with nucleic acid-based hydrogels can be leveraged for sequence-specific binding, representing a leap forward in biomaterials. Key findings: Special attention was given to the latest conjugation approaches and binding motifs that are useful for designing hydrogel-based drug delivery systems. The review systematically categorizes hydrogel conjugates for drug delivery, focusing on conjugating hydrogels with major classes of therapeutic agents, including small-molecule drugs, nucleic acids, proteins, etc., each with distinct conjugation challenges. The design principles were discussed along with their properties and drug release profiles. Finally, future opportunities and current limitations of conjugated hydrogel systems are addressed. Full article

Partially substituting other proteins in soy-protein-based products is an effective method to meet nutritional and application requirements. However, the emulsifying properties of soybean protein isolates (SPI) when partially substituted with zein hydrolysates (ZH) remain unknown. In the present work, protein blend (0 h-SPI/ZH) from SPI and ZH with a ratio of 3.5: 1 (w/w) was treated by transglutaminase (TGase) for 0, 0.5, 1.0, and 1.5 h, respectively. SDS-PAGE analysis results indicate protein polymers were generated in SPI/ZH conjugates. Emulsifying activity of the conjugates (1.5 h-SPI/ZH) was significantly increased from 23.69 to 28.13 m² g⁻¹ in comparison with SPI, and there was no statistically significant difference (p < 0.05) in emulsion stability. The apparent viscosity, surface hydrophobicity of the SPI/ZH conjugates were significantly increased. Emulsion droplet size and zeta potential stabilized by 1.5 h-SPI/ZH were also increased; the values were 64.73 to 80.79 r.nm and −21.8 to −29.9 mV, respectively. CLSM results indicate that 1.5 h-SPI/ZH conjugates stabilized the emulsion and had a thicker adsorption layer. Overall, high values of negative zeta potential and suitable molecular weight distribution of the SPI/ZH conjugates might be responsible for the improved emulsifying property. This study provides insights for the preparation of soy-protein-based products as a promising food emulsifier. Full article

Background: Ulcerative colitis (UC), a subtype of chronic inflammatory bowel disease (IBD), is primarily treated with oral medications to reduce inflammation and alleviate symptoms. Celecoxib (CXB) is an attractive candidate for UC; however, its limited solubility and low bioavailability pose significant challenges to its clinical application. Methods: We reported a novel chondroitin sulfate A–Celecoxib (CSA-CXB) polymeric nanoprodrug to address the limited solubility and low bioavailability of CXB. CXB was conjugated to chondroitin sulfate A (CSA) via succinic anhydride (SA) and ethylenediamine to prepare CSA-CXB polymers, which can self-assemble into nanoparticle structural prodrugs in aqueous condition. We investigated the stability, blood compatibility, and responsiveness of the nanoparticles. The ability of the nanoparticles to treat UC in vitro and in vivo was then evaluated. Results: The CSA-CXB nanoprodrug was spherical with a mean particle size of 188.4 ± 2.2 nm, a zeta potential of −22.9 ± 0.1 mV, and sustained drug release behavior. Furthermore, CSA-CXB exhibited remarkable antioxidant and anti-inflammatory effects, as it can significantly increase the free radical scavenging rate and reduce the expression level of ROS, TNF-α, IL-6, nitric oxide (NO), and COX-2 protein in vitro. In vivo results demonstrated that CSA-CXB targeted the mice’s colon efficiently mitigate UC symptoms by inhibiting the expression of inflammatory cytokine. Conclusions: The CSA-CXB nanoprodrug can improve the therapeutic impact of CXB, and has potential as a new preparation for a clinical UC treatment nanoprodrug. Full article

Background/Objectives: Paclitaxel (PTX) is a potent anticancer drug that is poorly soluble in water. To enhance its delivery efficiency in aqueous environments, amphiphilic polymer micelles are often used as nanocarriers for PTX in clinical settings. However, the hydrophilic polymer segments on the surface of these micelles may possess potential immunogenicity, posing risks in clinical applications. To address this issue, nanomicelles based on human serum albumin (HSA)–hydrophobic polymer conjugates constructed via site-specific in situ polymerization-induced self-assembly (SI-PISA) are considered a promising alternative. The HSA shell not only ensures good biocompatibility but also enhances cellular uptake because of endogenous albumin trafficking pathways. Moreover, compared to traditional methods of creating protein–hydrophobic polymer conjugates, SI-PISA demonstrates higher reaction efficiency and better preservation of protein functionality. Methods: We synthesized HSA-PMEMA nanomicelles via SI-PISA using HSA and methoxyethyl methacrylate (MEMA)—a novel hydrophobic monomer with a well-defined and stable chemical structure. The protein activity and the PTX intracellular delivery efficiency of HSA-PMEMA nanomicelles were evaluated. Results: The CD spectra of HSA and HSA-PMEMA exhibited similar shapes, and the relative esterase-like activity of HSA-PMEMA was 94% that of unmodified HSA. Flow cytometry results showed that Cy7 fluorescence intensity in cells treated with HSA-PMEMA-Cy7 was approximately 1.35 times that in cells treated with HSA-Cy7; meanwhile, HPLC results indicated that, under the same conditions, the PTX loading per unit protein mass on HSA-PMEMA was approximately 1.43 times that of HSA. These collectively contributed to a 1.78-fold overall PTX intracellular delivery efficiency of HSA-PMEMA compared to that of HSA. Conclusions: In comparison with HSA, HSA-PMEMA nanomicelles exhibit improved cellular uptake and higher loading efficiency for PTX, effectively promoting the intracellular delivery of PTX. Tremendous potential lies in these micelles for developing safer and more efficient next-generation PTX formulations for tumor treatment. Full article

Despite wide applications of CRISPR/Cas9 technology, effective approaches for CRISPR delivery with functional control are limited. In an attempt to develop a nanoscale CRSIPR/Cas9 delivery platform, we discovered that several biocompatible polymers, including polymalic acid (PMLA), polyglutamic acid (PGA), and polyaspartic acid (PLD), when conjugated with a trileucine (LLL) moiety, can effectively inhibit Cas9 nuclease function. The Cas9 inhibition by those polymers is dose-dependent, with varying efficiency to achieve 100% inhibition. Further biophysical studies revealed that PMLA-LLL directly binds the Cas9 protein, resulting in a substantial decrease in Cas9/sgRNA binding affinity. Transmission electron microscopy and molecular docking were performed to provide a possible binding mechanism for PMLA-LLL to interact with Cas9. This work identified a new class of Cas9 inhibitor in nano-polymer form. These biodegradable polymers may serve as novel Cas9 delivery vehicles with a potential to enhance the precision of Cas9-mediated gene editing. Full article

Hybrid hydrogels from protein–polymer conjugates are biomaterials formed via the chemical bonding of a protein molecule with a polymer molecule. Protein–polymer conjugates offer a variety of biological properties by combining the mechanical strength of polymers and the bioactive functionality of proteins. These properties allow these conjugates to be used as biocompatible components in biomedical applications. Protein–polymer conjugation is a vital bioengineering strategy in many fields, such as drug delivery, tissue engineering, and cancer therapy. Protein–polymer conjugations aim to create materials with new and unique properties by combining the properties of different molecular components. There are various ways of creating protein–polymer conjugates. PEGylation is one of the most common conjugation techniques where a protein is conjugated with Polyethylene Glycol. However, some limitations of PEGylation (like polydispersity and low biodegradability) have prompted researchers to devise novel synthesis techniques like PEGylation, where synthetic polypeptides are used as the polymer component. This review will illustrate the properties of protein–polymer conjugates, their synthesis methods, and their various biomedical applications. Full article

Fibroin, a protein extracted from silk, offers advantageous properties such as non-immunogenicity, biocompatibility, and ease of surface modification, which have been widely utilized for a variety of biomedical applications. However, in vivo studies have revealed critical challenges, including rapid enzymatic degradation and limited stability. To widen the scope of this natural biomacromolecule, the grafting of polymers onto the protein surface has been advanced as a platform to enhance protein stability and develop smart conjugates. This review article brings into focus applications of fibroin-hybrid systems prepared using chemical modification of the protein with polymers and inorganic compounds. A selection of recent preclinical evaluations of these hybrids is included to highlight the significance of this approach. Full article

Since its conceptualization, click chemistry in all its variants has proven to be a superior synthesis protocol, compared to conventional methods, for forming new covalent bonds under mild conditions, orthogonally, and with high yields. If a term like reactive resilience could be established, click reactions would be good examples, as they perform better under increasingly challenging conditions. Particularly, highly hindered couplings that perform poorly with conventional chemistry protocols—such as those used to conjugate biomacromolecules (e.g., proteins and aptamers) or multiple drugs onto macromolecular platforms—can be more easily achieved using click chemistry principles, while also promoting high stereoselectivity in the products. In this review, three molecular platforms relevant in the field of nanomedicine are considered: polymers/copolymers, cyclodextrins, and fullerenes, whose functionalization poses a challenge due to steric hindrance, either from the intrinsic bulk behavior (as in polymers) or from the proximity of confined reactive sites, as seen in cyclodextrins and fullerenes. Their functionalization with biologically active groups (drugs or biomolecules), primarily through copper-catalyzed azide–alkyne cycloaddition (CuAAC), strain-promoted azide–alkyne cycloaddition (SPAAC), inverse electron-demand Diels–Alder (IEDDA) and thiol–ene click reactions, has led to the development of increasingly sophisticated systems with enhanced specificity, multifunctionality, bioavailability, delayed clearance, multi-targeting, selective cytotoxicity, and tracking capabilities—all essential in the field of nanomedicine. Full article

Background: Acrylamide polymers with zwitterionic carboxybetaine (CB) side groups have attracted attention as stealth polymers that do not induce antibodies when conjugated to proteins. However, they induce antibodies when modified onto liposomes. We hypothesized that antibodies are produced against polymer backbones rather than CB side groups. Objectives: In this study, we designed and synthesized a polymer employing CB in its main chain, poly(N-acetic acid-N-methyl-propyleneimine) (PAMPI), and evaluated the blood retention of PAMPI-modified liposomes in mice. Results: The non-fouling nature of PAMPI-modified liposomes estimated from serum protein adsorption was found to be not inferior to PCB- and PEG-modified liposomes. However, to our surprise, the PAMPI-modified liposomes showed an instantaneous clearance less than 1 h post-injection, comparable to the naked liposomes. Conclusions: The extent of the blood retention of polymer-modified liposomes cannot be predicted by their susceptibility to serum protein adsorption and semi-flexible conformation. Full article

Gold nanoparticles (AuNPs) play a vital role in biotechnology, medicine, and diagnostics due to their unique optical properties. Their conjugation with antibodies, antigens, proteins, or nucleic acids enables precise targeting and enhances biosensing capabilities. Functionalized AuNPs, however, may experience reduced stability, leading to aggregation or loss of functionality, especially in complex biological environments. Additionally, they can show non-specific binding to unintended targets, impairing assay specificity. Within this work, citrate-stabilized and silica-coated AuNPs (GNPs and SiGNPs, respectively) have been coated using N,N-dimethylacrylamide-based copolymers to increase their stability and enable their functionalization with biomolecules. AuNP stability after modification has been assessed by a combination of techniques including spectrophotometric characterization, nanoparticle tracking analysis, transmission electron microscopy and functional microarray tests. Two different copolymers were identified to provide a stable coating of AuNPs while enabling further modification through click chemistry reactions, due to the presence of azide groups in the polymers. Following this experimental design, AuNPs decorated with ssDNA and streptavidin were synthesized and successfully used in a biological assay. In conclusion, a functionalization scheme for AuNPs has been developed that offers ease of modification, often requiring single steps and short incubation time. The obtained functionalized AuNPs offer considerable flexibility, as the functionalization protocol can be personalized to match requirements of multiple assays. Full article

Block copolymer (BCP) surfaces permit an exquisite level of nanoscale control in biomolecular assemblies solely based on self-assembly. Owing to this, BCP-based biomolecular assembly represents a much-needed, new paradigm for creating nanobiosensors and nanobiomaterials without the need for costly and time-consuming fabrication steps. Research endeavors in the BCP nanobiotechnology field have led to stimulating results that can promote our current understanding of biomolecular interactions at a solid interface to the never-explored size regimes comparable to individual biomolecules. Encouraging research outcomes have also been reported for the stability and activity of biomolecules bound on BCP thin film surfaces. A wide range of single and multicomponent biomolecules and BCP systems has been assessed to substantiate the potential utility in practical applications as next-generation nanobiosensors, nanobiodevices, and biomaterials. To this end, this Review highlights pioneering research efforts made in the BCP nanobiotechnology area. The discussions will be focused on those works particularly pertaining to nanoscale surface assembly of functional biomolecules, biomolecular interaction properties unique to nanoscale polymer interfaces, functionality of nanoscale surface-bound biomolecules, and specific examples in biosensing. Systems involving the incorporation of biomolecules as one of the blocks in BCPs, i.e., DNA–BCP hybrids, protein–BCP conjugates, and isolated BCP micelles of bioligand carriers used in drug delivery, are outside of the scope of this Review. Looking ahead, there awaits plenty of exciting research opportunities to advance the research field of BCP nanobiotechnology by capitalizing on the fundamental groundwork laid so far for the biomolecular interactions on BCP surfaces. In order to better guide the path forward, key fundamental questions yet to be addressed by the field are identified. In addition, future research directions of BCP nanobiotechnology are contemplated in the concluding section of this Review. Full article

The repair of critical-sized calvarial defects is a challenging problem for orthopedic surgery. One of the promising strategies of bone bioengineering to enhance the efficacy of large bone defect regeneration is the combined delivery of stem cells with osteoinductive factors within polymer carriers. The purpose of the research was to study the regenerative effects of heparin-conjugated fibrin (HCF) hydrogel containing bone morphogenetic protein 2 (BMP-2) and adipose-derived pericytes (ADPs) in a rat critical-sized calvarial defect model. In vitro analysis revealed that the HCF hydrogel was able to control the BMP-2 release and induce alkaline phosphatase (ALP) activity in neonatal rat osteoblasts. In addition, it was found that eluted BMP-2 significantly induced the osteogenic differentiation of ADPs. It was characterized by the increased ALP activity, osteocalcin expression and calcium deposits in ADPs. In vivo studies have shown that both HCF hydrogel with BMP-2 and HCF hydrogel with pericytes are able to significantly increase the regeneration of critical-sized calvarial defects in comparison with the control group. Nevertheless, the greatest regenerative effect was found after the co-delivery of ADPs and BMP-2 into a critical-sized calvarial defect. Thus, our findings suggest that the combined delivery of ADPs and BMP-2 in HCF hydrogel holds promise to be applied as an alternative biopolymer for the critical-sized bone defect restoration. Full article

Lycorine is a kind of natural active ingredient with a strong antitumor effect. In this study, folate ligand-conjugated polyethylene glycol-block-poly(l-lactide) (PEG-PLLA) nanoparticles (FA-PEG-PLLA NPs) were designed to deliver lycorine to enhance its anti-glioma activity. The successful preparation of the FA-PEG-PLLA polymer was confirmed by ¹H-NMR, FT-IR, XRD, TGA, and DSC. The optimal formulation for LYC@FA-PEG-PLLA NPs was determined by response surface analysis as follows: sodium dodecyl sulfate (SDS) of 1%, carrier material of 0.03 g, organic phase volume of 3 mL, and ultrasonic power of 20%. The LYC@FA-PEG-PLLA NPs exhibited an encapsulation efficiency of 83.58% and a particle size of 49.71 nm, demonstrating good stability. Hemolysis experiments, MTT assays, and cell scratch assays revealed excellent biocompatibility of FA-PEG-PLLA and superior anti-glioma activity of LYC@FA-PEG-PLLA NPs compared to the raw drug. Additionally, cell apoptosis assays, ROS experiments, and western blot analysis demonstrated that LYC@FA-PEG-PLLA NPs contributed to cell apoptosis by inducing ROS generation and increasing the expression of NF-κB inhibitory protein IκBα. These results suggested that LYC@FA-PEG-PLLA NPs hold promise for glioma treatment. Full article

The development of convective technologies for antibody purification is of interest to the bioprocessing industries. This study developed a Protein A membrane using a combination of graft polymerization and copper(I)-catalyzed alkyne–azide click chemistry. Regenerated cellulose supports were functionalized via surface-initiated copolymerization of propargyl methacrylate (PgMA) and poly(ethylene glycol) methyl ether methacrylate (PEGMEMA₃₀₀), followed by a reaction with azide-functionalized Protein A ligand. The polymer-modified membranes were characterized using attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR), gravimetric analysis, and permeability measurements. Copolymer composition was determined using the Mayo–Lewis equation. Membranes clicked with azide-conjugated Protein A were evaluated by measuring static and dynamic binding (DBC₁₀) capacities for human immunoglobulin G (hIgG). Copolymer composition and degree of grafting were found to affect maximum static binding capacities, with values ranging from 5 to 16 mg/mL. DBC₁₀ values did not vary with flow rate, as expected of membrane adsorbers. Full article

Degradable polymers (both biomacromolecules and several synthetic polymers) for biomedical applications have been promising very much in the recent past due to their low cost, biocompatibility, flexibility, and minimal side effects. Here, we present an overview with updated information on natural and synthetic degradable polymers where a brief account on different polysaccharides, proteins, and synthetic polymers viz. polyesters/polyamino acids/polyanhydrides/polyphosphazenes/polyurethanes relevant to biomedical applications has been provided. The various approaches for the transformation of these polymers by physical/chemical means viz. cross-linking, as polyblends, nanocomposites/hybrid composites, interpenetrating complexes, interpolymer/polyion complexes, functionalization, polymer conjugates, and block and graft copolymers, are described. The degradation mechanism, drug loading profiles, and toxicological aspects of polymeric nanoparticles formed are also defined. Biomedical applications of these degradable polymer-based biomaterials in and as wound dressing/healing, biosensors, drug delivery systems, tissue engineering, and regenerative medicine, etc., are highlighted. In addition, the use of such nano systems to solve current drug delivery problems is briefly reviewed. Full article