Drug Conjugation Services

Drug conjugation is an advanced drug delivery strategy, which is the process of covalently linking drugs or prodrugs to various natural or synthetic molecule carriers to form drug conjugates, thereby achieving targeted delivery and release of drugs. Drug conjugate technology has made important breakthroughs in the field of drug research and development and has shown great potential in clinical practice. As a professional biotech company, BOC Sciences offers comprehensive bioconjugation services for wide range of drug conjugates consisting of alternative carriers, payloads and linkers that can be designed and developed according to your specific project goals. We have extended drug conjugation to a variety of new modes, of which carriers include antibodies, peptides, aptamers, and small molecules; payloads include drug molecules, oligonucleotides, proteins, biopolymers, and more.

What are Drug Conjugates?

Drug conjugates, composed of a drug payload, a linker molecule, and a carrier molecule, represent a revolutionary class of therapeutics that precisely deliver drugs to their intended targets, minimizing collateral damage and side effects. The process of conjugation can regulate the ratio of drug molecules to carriers. The efficacy of drug conjugates depends on the ability of the carrier molecule, often an antibody, to bind selectively to target cells, followed by internalization and the controlled release of the drug payload, which can exert its therapeutic effect with remarkable precision. This precision makes drug conjugates invaluable in various medical fields, including oncology, infectious diseases, autoimmune disorders, and even neurology, promising improved treatment outcomes and reduced side effects.

Fig.1 Drug conjugates are composed of carrier, linker and payload. (Heh, E., 2023)

Classification of Drug Conjugates

1. Targeted Drug Conjugates (TDCs)

This type of drug conjugate achieves tumor killing of cell tumors by connecting drugs with molecules targeting specific cell surfaces. Common drug conjugates include pro-, pro-fragment, ligand, etc. TDCs can improve the therapeutic effect of drugs and reduce the toxicity to normal cells by presetting molecular specific structures.

2. Carrier Drug Conjugates (CDCs)

This type of drug conjugate connects drugs to carrier molecules, and uses the characteristics of the carrier molecules to achieve drug delivery and enhanced release. Common carrier molecules include carriers, nanoparticles, matrices, etc. CDCs can improve the solubility, stability and inhibition of drugs, thereby improving the therapeutic effect of drugs.

3. Dual Drug Conjugates (DDCs)

This type of drug conjugate connects two different drug molecules together to achieve a stronger therapeutic effect through combined action. Common tumor dual-drug conjugates include anti-drugs and immunomodulators, antiviral drugs and modulators. DDCs can improve the therapeutic effect and reduce the occurrence of inflammation through the good effects of different drugs.

Drug Conjugation Techniques

Conjugation techniques are a family of chemical processes that enable the coupling of two or more molecules to create a new entity with distinct properties and applications.

Chemical Conjugation: Chemical conjugation methods include the use of reactive functional groups like amines, thiols, and carboxyl groups to form covalent bonds between molecules. And non-covalent bonds such as hydrogen bonds, ionic interactions, and van der Waals forces. They are generally weaker and less stable than covalent bonds but allow for easier detachment of the drug.

The wide array of available chemical reactions makes this technique valuable in the synthesis of drugs, polymers, and bioconjugates.

Enzymatic Conjugation: Enzymatic reactions, driven by enzymes with high specificity and efficiency, offer a gentler and more selective approach to conjugation. This technique is frequently used in the bioconjugation of proteins, antibodies, and peptides, as well as in the modification of DNA and RNA.

Click Chemistry: Click chemistry is a subset of chemical conjugation known for its efficiency and bioorthogonality, meaning the reactions do not interfere with biological systems. This is a type of chemical reaction that joins small units together with high yield and without side products. It is often used to efficiently create drug conjugates.

Site-Specific Conjugation: Site-specific conjugation techniques are designed to attach molecules at precise locations on larger entities. For example, non-canonical amino acids, the synthetic or modified amino acids, can be incorporated into carrier molecules, offering highly targeted attachment points for drug molecules. A wide range of methods have been developed in the pursuit of homogeneity, comprising chemical or enzymatic methods or a combination thereof to afford precise modification of specific amino acid or sugar residues.

Advantages of Drug Conjugation

Targeted Therapy: Drug conjugation techniques allow the targeted delivery of drugs to specific cells, limiting the impact on healthy tissues and reducing side effects.

Improved Efficacy: By conjugating drugs with substances that enhance penetration through the cell membrane, the drug's efficacy can be significantly increased.

Enhanced Bioavailability: Drug conjugation can improve the bioavailability of drugs, as the conjugated molecules can facilitate the transport of drug molecules across biological barriers.

Controlled Drug Release: Some conjugation methods allow for controlled drug release, ensuring that the drug is delivered to the target site over an extended period.

Increased Solubility: Conjugating a drug with a water-soluble substance can increase the solubility of the drug, making it easier for the body to absorb.

Reduced Dosage Requirement: Due to the increased efficacy and bioavailability of conjugated drugs, the required dosage can often be reduced. This can lower the risk of overdose and decrease the incidence of side effects.

Improved Patient Compliance: The reduced frequency of dosing due to the controlled release characteristic of many conjugated drugs can lead to improved patient compliance.

Good Pharmacokinetic Properties: Drug conjugates are usually designed to release drugs under specific conditions. By controlling the release of drugs, they can reduce the decomposition and excretion of drugs in the body and prolong the action time of drugs.

Drug Stability: Conjugation can improve the stability of drugs, protecting them from degradation before they reach the targeted site.

Broad Applicability: Various types of drugs, ranging from small molecules to biologics, can be conjugated, this broadens the use of this technology to a wide range of therapeutic areas.

Linker Technology in Drug Conjugation

Linker technology, a crucial component of conjugation techniques, serves as the bridge connecting two or more molecules in a conjugate. Linkers are pivotal in controlling the release, stability, and spatial arrangement of the entities they connect.

Cleavable Linkers: Cleavable linkers are designed to break under specific conditions, releasing the connected molecules. The cleavable linkers can be further divided into pH-sensitive, enzyme-sensitive and redox-sensitive. For example, orthoester linkers are sensitive to acidic conditions and can be cleaved under low pH, such as within endosomes or lysosomes; peptide linkers are composed of amino acids and can be cleaved by proteolytic enzymes present within cells; disulfide linkers are susceptible to reduction by glutathione, a molecule abundant in the intracellular environment.

Fig.2 Cleavable linkers. (Heh, E., 2023)

Non-Cleavable Linkers: Non-cleavable linkers, in contrast, remain stable, ensuring that the molecules in a conjugate are connected throughout their journey. This type of linker is often used to create stable, long-lasting bioconjugates.

Spacer Linkers: Spacer linkers are designed to keep the connected molecules at a defined distance from each other. This distance can be critical in maintaining the binding affinity and function of molecules in a conjugate.

Drug Conjugation Service

With our expertise in organic synthesis, protein genetic engineering, and medicinal chemistry, BOC Sciences is well-equipped to contribute to various drug conjugates.

Competitive Advantages

Expertise and Experience: We have a deep expertise in drug conjugation and a proven track record in the industry. Our team comprises of highly qualified professionals with years of experience in drug conjugation.

Advanced Techniques: We leverage the latest and advanced drug conjugation techniques to provide our clients with the most effective solutions. Our advanced methods expand the therapeutic window and increase the efficacy of drugs.

Advanced Analysis Methods: HPLC, UPLC, LCMS, UV, FL, cSDS, cIEF, CZE, DSC, TGA, ELISA, DLS, HIA.

Customization: We understand that every drug is unique, and so are your requirements. We offer customized drug conjugation services tailored to specific client needs.

Quality Assurance: Our drug conjugation services adhere to the highest quality standards. We use thorough testing methods to ensure the safety and efficacy of the drugs we work on.

Regulatory Compliance: We stay up-to-date with the latest industry regulations and maintain compliance with all laws and guidelines.

Cost-effective Solutions: We provide cost-effective drug conjugation services without compromising on the quality of the work.

Time Efficiency: We understand the critical nature of drug development and hence ensure timely delivery of our services. Our efficient processes and dedicated team enable us to meet strict timelines.

Confidentiality: We strictly maintain the confidentiality of all client information and data, ensuring complete security and privacy.

Client-Centric Approach: Client satisfaction is our ultimate goal. We work closely with our clients, keeping them updated at every stage of the project, and addressing their queries promptly.

Global Reach: We have a global client base, which showcases our capability to manage diverse projects across different geographical locations.

Case Study

Case Study 1

Antibody-drug conjugates (ADCs) have developed rapidly, and 14 of them have received market approval since the first approval event by the Food and Drug Administration in 2000. However, there are some limitations in the use of antibodies as carriers. Other classes of drug conjugates are emerging, such as targeted drugs conjugated with peptides (peptide-drug conjugates, PDCs) and polymers (polymer-drug conjugates, PolyDCs) with the remaining constructs similar to those of ADCs. These novel drug conjugates are gaining attention because they overcome the limitations of ADCs. Bispecific ADCs (bsADCs) can increase tumor specificity and selectivity, and limited co-expression of bispecific antigens in normal tissues can potentially reduce off-target toxicity. Moreover cooperative binding leads to a higher internalization rate and increased payload disposition in tumor tissues. The connection between the two peptide components (TTP and CPP) can be achieved through a linker peptide that can be recognized and cleaved by cell surface enzymes to overcome the drawbacks of TTP- or CPP- drug conjugates. Drugconjugate-based nanocombination is an advanced strategy to enhance the stability of small molecules in the circulation system and minimize their off-target effects.

Fig.3 Categories of current advanced drug-conjugates. (Yang, Y.Q., 2023)

Case Study 2

A recent dual-functional approach demonstrates the use of nanoparticles to increase the stability of a prodrug PDC. The rationale behind the design was based around photothermal therapy (PTT), a non-invasive form of antitumour therapy that involves the use of near-infrared (NIR) light. The design used a hollow Cu sulphide nanoparticle (HCuS) to encapsulate the PDC (cRGD-SMCC-DM1). The PDC comprises of three components: the integrin RGD homing peptide, the SMCC non-cleavable thioether linker and the DM1 cytotoxic payload. HCuS nanoparticles present a fluorescently labelled amphiphilic copolymer fPEDC on the surface, termed P@HCuS. fPEDC copolymers promote several properties: they act as a chromophore for detection, aid stabilisation and are pH/redox-sensitive. Maximum distribution was observed after 24 hours from the injection of the PDC/P@HCuS complex in MDA-MB-231 tumour bearing mice. Laser irradiation localised the complex both intraand extracellularly. The fPEDC is redox/pH-sensitive and hence the linker was cleaved inside the tumour cells. The extracellular PDCs, through a process of receptor-mediated endocytosis, entered the cells and enzymatically degraded in the lysosome where DM1 was released. The nanosystem construct PDC/P@HCuS had excellent circulation times with up to 3 weeks of anti-tumour efficacy from initial NIR laser irradiation.

Fig.4 Schematic Illustration of the Design and Chemo-Photothermal Therapy of a Nanocombination (PDC/P@HCuS) Based on Imaging Associated with Peptide−Drug Conjugates. (Sun, Y., 2019)

FAQ

1. What types of drug conjugates do you produce?

We provide a wide range of drug conjugates, encompassing antibody-drug conjugates, peptide-drug conjugates, and protein-drug conjugates. We also offer customization to meet specific client requirements.

2. What is the role of drug conjugates in targeted therapy?

Drug conjugates play a crucial role in targeted therapy. They have the ability to selectively deliver drugs to specific cells, primarily cancer cells, reducing the impact on healthy tissues and thereby minimizing side effects.

3. What are the potential applications of drug conjugation?

Drug conjugations are used in various areas of research and therapeutics, including targeted therapy, drug delivery, imaging, immunoassays, and diagnostic tests. They can help improve drug specificity, stability, solubility, and efficacy.

4. How do you ensure the quality of your drug conjugation services?

We adhere to rigorous quality control and assurance protocols throughout the conjugation process, using advanced testing and analytical techniques to ensure purity, stability and bioactivity of the final product.

5. How long does the drug conjugation process typically take?

The timeline for drug conjugation varies based on project complexity, but typically ranges from a few weeks to several months. We provide detailed timelines and regular project updates to keep clients informed.

6. What are the costs associated with your drug conjugation services?

Pricing for our drug conjugation services varies based on several factors, including the type and quantity of the drug conjugate, the complexity of the project, and any additional services required. We strive to provide cost-effective solutions and can provide a detailed quote upon request.