Protein-Nanoparticles Conjugates Services


Protein-nanoparticles bioconjugates have shown great potential for applications in biomedicine and life sciences, including drug delivery and diagnostics. As a leading producer and supplier of nanoparticles products, CD Bioparticles specializes in the preparation of protein-nanoparticles conjugates using polymerization techniques, to meet your research and production needs. We have a team of experienced R&D scientists and advanced equipment platforms that can support the functionalization of cysteine (Cys), lysine (Lys), tyrosine (Tyr), glutamine (Gln) and unnatural amino acids side chain and terminal proteins are functionalized. We have experience in conjugating different proteins and nanoparticles, and provide in vitro and in vivo characterization services according to our clients' project needs.

Introduction to Protein-Nanoparticles Conjugates

Proteins play central roles in most biological processes, including functions such as structure shaping, catalyzing reactions, and transport of substances. These unique properties stem from their distinct monomer sequences and complex three-dimensional structures. The specificity of proteins makes them suitable for many fields, and synthetic nanoparticles further enhance their application value. Protein-nanoparticles conjugates play an important role as key materials in the fields of biotechnology, nanotechnology, and medicine. Protein-nanoparticles conjugates exhibit superior properties compared to native proteins, including enhanced stability and solubility.

Figure 1. Protein-nanoparticle interactions.Figure 1. Protein–nanoparticle interactions: main factors that can affect proteins resulting in their denaturation. (Di Marco M, et al.; 2010)

Protein-nanoparticles conjugates are products that incorporate features of biomacromolecules, aiming to exhibit the versatility and structural features of their synthetic and biological components. Certain natural proteins have decreased stability under non-physiological conditions, are susceptible to enzymatic degradation, trigger adverse immune reactions, and cannot cross most biological barriers, even below the threshold of renal filtration. The development of protein-nanoparticles conjugates is mainly to overcome these limitations, improve the stability, solubility, biodistribution, circulation half-life and reduce antigenicity of these proteins. Furthermore, the chemical diversity of nanoparticles endows natural biomacromolecules with the potential to enhance performance.

The specific features of protein-nanoparticles conjugates include:

  • Retention of biological activity: One of the main goals of protein-nanoparticles conjugation is to retain the biological activity of the protein component.
  • Enhanced stability: Nanoparticles can provide stability to proteins, protecting them from degradation, denaturation, and other environmental factors that can lead to loss of activity. This enhanced stability is especially beneficial for proteins that are sensitive to changes in temperature, pH, or other conditions.
  • Tunable Solubility: Nanoparticles can affect the solubility of proteins, which is especially useful for proteins that are poorly soluble in aqueous solutions. By conjugation with nanoparticles, the solubility of these proteins can be increased, making them easier to handle and formulate.
  • Prolonged circulation time: In the case of drug delivery, protein-nanoparticles conjugates can exhibit prolonged blood circulation time. This is due to the "stealth" effect imparted by the nanoparticle, which reduces recognition by the immune system and helps avoid rapid clearance.
  • Controlled Release: Nanoparticles can be designed to provide controlled release of protein payloads over time. This property is crucial in drug delivery applications, where sustained and controlled release of therapeutic proteins can improve therapeutic efficacy and reduce side effects.
  • Targeting and specificity: Nanoparticles can be functionalized with targeting ligands or antibodies to direct protein-nanoparticles conjugates to specific cells, tissues or organs. This enhances the specificity of the conjugate, reduces off-target effects and improves therapeutic outcomes.
  • Size and shape tuning: The size and shape of protein-nanoparticles conjugates can be controlled by the choice of nanoparticles and conjugation method. This affects the biodistribution, cellular uptake and overall performance of the conjugate.
  • Versatility: Nanoparticles can be engineered to perform multiple functions, such as binding imaging agents, contrast agents, or other payloads. This enables the protein-nanoparticles conjugates to be used as both therapeutic and diagnostic tools.
  • Biocompatibility: Many nanoparticles used for protein conjugation are biocompatible, meaning they do not cause strong immune responses or toxicity in the body. This is crucial for applications in medicine and biotechnology.

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  • Preparation Method of Side Chain Protein Nanoparticles

Various controllable radical polymerization techniques can be used to synthesize side-chain functional nanoparticles. In this approach, monomers with side groups susceptible to chemoselective reactions are polymerized in protected or unprotected form and then reacted with the appropriate functional protein. CD Bioparticles can provide comprehensive custom synthesis services of side chain functional nanoparticles, including active esters with side groups, protected or free ketones and aldehydes, protected maleimides, protected alkynes, azides and p-aryl halide monomer.

  • Synthesis of End Group Protein Nanoparticles

End-group protein-reactive nanoparticles can be prepared by a variety of controlled or living polymerization techniques with appropriate functional initiators. These initiators are designed to be inactive for polymerization in their native or protected state and can be activated after polymerization. In addition, functional terminators are capable of terminating the polymerization process, thereby imparting functionality to the end of the nanoparticles. CD Bioparticles utilizes suitable functional initiators to prepare end-group protein nanoparticles, such as α-functionalized nanoparticles and omega-functionalized nanoparticles.

  • Synthesis of Protein-Templated Nanoparticles

Denatured protein-based peptide-PEG conjugates can be used in a variety of biomedical applications, or as substrates for precise nanomaterial synthesis. This method has been widely used to synthesize linear nanoparticles with defined chain lengths and functional groups at specific positions within the chains by acylation of denatured proteins. Currently, denatured protein-PEG conjugates are widely used in the industry. CD Bioparticles is able to design PEG chains of different molecular weights and attach them to denatured proteins via covalent linkages such as thiol-maleimide or amine-NHS ester. In addition, we also provide custom protein cage-based nanoparticles conjugation services.

  • Self-assembly of Protein-Nanoparticles Conjugates

In recent years, self-assembled nanoparticles based on protein-nanoparticles conjugates have been extensively studied as carriers for carrying anticancer drugs. These self-assembled nanostructures have special intrinsic biological activities due to the presence of proteins. CD Bioparticles can self-assemble protein-nanoparticles conjugates into fibers, vesicles, and ring structures.

  • Surface Deposition of Protein-Nanoparticles Conjugates

Due to their strength, versatility, and good processability, synthetic nanoparticles are widely used to immobilize biomolecules, including peptides and enzymes, on various surfaces, offering potential applications in areas such as biosensors, biotechnology, and biomedical devices. CD Bioparticles can be used to construct attractive functional surfaces with biological activity, such as antibacterial and cell adhesion properties, by direct deposition of nanoparticles bioconjugates or stepwise immobilization of nanoparticles and biomolecules on the surface.

The applications of protein-nanoparticles conjugates include:

Protein therapy: Protein-nanoparticles conjugates have been studied and widely used in clinical research. The applicability of protein therapeutics has been greatly expanded since nanoparticles conjugation can often enhance the stability, functional activity, and prolong blood circulation time of therapeutic proteins. It is worth noting that structural factors during protein-nanoparticles conjugation, including the conjugation site, graft density, and nanoparticles length, may affect the bioactivity and therapeutic efficacy of the conjugate.

Drug delivery vehicles or coatings: Protein-nanoparticles conjugates and their assemblies have also been used as vehicles or coatings for drug delivery. In addition to their use in protein and drug delivery in cancer therapy, structurally defined protein-nanoparticles conjugates have also been applied in the construction of biomaterials, such as fluorescent nanoprobes and cell matrices.

Biomedical materials: Protein-nanoparticles bioconjugates also provide biomedical fields with materials with rich biological functions, such as cell targeting and antibacterial properties, and expand their applications in multiple fields.

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References

  1. Weil, T. et al.; Polymer bioconjugates: Modern design concepts toward precision hybrid materials. Progress in Polymer Science. 2020, 105: 101241.
  2. Klok, H.A. et al.; Peptide/protein-polymer conjugates: synthetic strategies and design concepts. Chem. Commun. 2008, 2591-2611.
  3. Di Marco M, et al.; Overview of the main methods used to combine proteins with nanosystems: absorption, bioconjugation, and encapsulation. Int J Nanomedicine. 2010, 5:37-49.
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