Bioconjugation

Bioconjugation refers to the process of chemically linking two molecules to form a single hybrid compound. Typically, it involves attaching a biomolecule (like a protein, antibody, peptide, or nucleic acid) to another functional molecule, such as a drug, fluorescent dye, or nanoparticle. This technique is essential in fields like drug delivery, diagnostics, imaging, and therapeutics.

Common bioconjugation strategies involve targeting specific functional groups (e.g., amines, thiols, carboxyls) to ensure controlled and site-specific coupling. The resulting conjugates retain the biological activity of the original molecules while gaining new functions, making bioconjugation a powerful tool in biotechnology and biomedical research.

In bioconjugation, the choice of linker chemistry is critical for achieving stable, specific, and efficient attachment between two molecules. Linkers can influence biological activity, pharmacokinetics, and release mechanisms of conjugated compounds, especially in applications like antibody-drug conjugates (ADCs), imaging agents, or nanoparticle functionalization.

🔗 Linker Chemistry

Linkers are chemical moieties that bridge two biomolecules or a biomolecule and a functional group. They can be:

• Cleavable (e.g., pH-sensitive, enzyme-sensitive, or redox-sensitive), allowing controlled release.
• Non-cleavable, offering permanent conjugation for stability.

Linkers are often tailored for:

• Site-specificity (to reduce off-target effects)
• Biocompatibility
• Reactivity with target functional groups (e.g., amines, thiols, carboxyls)

linker design is central to modern bioconjugation strategies. It enables the creation of highly functional, targeted biomolecular constructs with applications in drug delivery, biosensing, therapeutics, and bioimaging.

Dr. Daniel Liu has extensive experience in the field of bioconjugation, with a research focus on the design and development of protein-drug conjugates, lipid nanoparticle-based conjugates, and monoclonal antibody–lipid (mAb–lipid) conjugates. His work has explored innovative strategies for linking therapeutic agents to biomolecules, enabling targeted delivery and enhanced efficacy in drug delivery systems. By integrating expertise in linker chemistry and nanoparticle formulation, Dr. Liu has contributed to the advancement of next generation bioconjugate platforms for therapeutic and diagnostic applications and he could be able to provide best solutions for your bioconjugation needs. See below for some examples he performed.

Related Publications by Dr. Liu

1. A novel protein-drug conjugate, SSH20, demonstrates significant efficacy in caveolin-1-expressing tumors Scientists have developed a new cancer drug called SSH20, which combines the chemotherapy agent SN-38 (insoluble in aqueous phase) with human serum albumin (HSA) to help it target tumors more effectively. This drug works especially well in cancers that have high levels of a protein called Caveolin-1 (Cav-1), which helps cancer cells take in albumin. When Cav-1 levels were reduced in cells or tumors, the uptake and effectiveness of SSH20 dropped significantly. Compared to the standard chemotherapy drug irinotecan (a prodrug of SN-38), SSH20 was more powerful both in lab tests and in mice. These findings suggest that SSH20 could be a safer and more targeted treatment for cancers with high Cav-1 expression.
2. Folate receptor-targeted lipid-albumin nanoparticles (F-LAN) for therapeutic delivery of an Akt1 antisense oligonucleotide RX-0201 is an antisense drug targeting Akt1, a protein involved in cancer growth, and is currently in clinical trials for metastatic kidney cancer. This study aimed to improve RX-0201 delivery using folate receptor-targeted lipid-albumin nanoparticles (F-LAN). These nanoparticles were designed to better target cancer cells that overexpress folate receptors. In both lab and animal studies, F-LAN loaded with RX-0201 showed higher drug uptake, stronger inhibition of cancer cell growth, longer circulation time in the body, and greater tumor suppression compared to non-targeted formulations or the free drug. Overall, F-LAN-RX-0201 shows promise as an improved delivery system for treating folate receptor-positive tumors.
3. T7 peptide-conjugated lipid nanoparticles for dual modulation of Bcl-2 and Akt-1 in lung and cervical carcinomas Bcl-2 and Akt1 are proteins linked to cancer progression, and while antisense oligonucleotides (ASOs) like G3139 and RX-0201 target them, their clinical effectiveness has been limited. This study developed improved, chemically modified ASOs using a “Gapmer” design and delivered them via transferrin receptor-targeting lipid nanoparticles (LNPs). These LNPs, loaded with either single or combined ASOs (Co-ASOs), showed excellent stability, efficient cellular uptake, and strong gene-silencing effects in cancer cell models. In mouse models, the targeted Co-ASO LNPs significantly reduced tumor growth, enhanced survival, and effectively suppressed both Bcl-2 and Akt1, showing promise for combination gene-targeted cancer therapy.
4. Topical Lyophilized Targeted Lipid-Nanoparticles in the Restoration of Skin Barrier Function Following Burn Wound This study developed lyophilized keratinocyte-targeted lipid nanoparticles (TLNκ) to deliver locked nucleic acid (LNA)-modified anti-miR-107 for topical treatment of full-thickness burn injuries. TLNκ were engineered with a targeting peptide to selectively deliver the therapy to keratinocytes, while pH-responsive lipids enhanced cellular uptake and endosomal escape. The nanoparticles showed high encapsulation efficiency and stability, with over 90% keratinocyte uptake within 4 hours. In a burn wound model, topical application of TLNκ carrying anti-miR-107 significantly accelerated wound healing, enhanced skin barrier restoration, and promoted keratinocyte differentiation by depleting miR-107 and upregulating dicer and junctional proteins. These results support TLNκ as a promising topical therapy for burn wound healing.