Nanocarriers are potential payloads in the strategy of ADC development. Nanocarriers have the capacity to deliver a significant amount of therapeutic agents at the disease site for the treatment of various diseases.
Figure: Synthetic schemes for conjugating antibodies to the nanocarriers using periodate oxidation (Antibody-Drug Conjugates, 2013)
Nanoparticles have a characteristic size, generally 1-1000nm and preferably 5-200nm, which is suitable for drug delivery. As a novel strategy, nanoparticles have received much attention in recent years. The designed nanocarriers often have unique physicochemical properties to improve the pharmacokinetic and biodistribution of drugs. In comparison with free drugs, nanocarriers have many advantages. Firstly, they protect the drug from premature degradation and interacting with the biological environment. Secondly, they enhance the absorption of drugs into a selected tissue. Finally, they improve intracellular penetration. Generally, therapeutic nanocarriers include lipid-based particles (e.g. liposomes), polymeric nanocarriers, etc. Liposomes are self-assembled colloidal spherical vesicle possessing a lipid bilayer membrane. The bilayer consists of amphiphilic phospholipids, which allows hydrophilic anticancer drugs or siRNA with aqueous core to be encapsulated and host hydrophobic agents in the hydrophobic membrane. Polymeric nanocarriers are a family of polymer-based nanocarriers mainly including polymeric micelles, dendrimers and polymeric nanoparticles. Polymeric micelles have amphiphilic core/shell to facilitate the delivery of poorly soluble agents. Dendrimers are hyperbranched macromolecules (10-100nm) with adjustable biocompability and pharmacokinetics. Polymeric nanoparticles are capsules/particles and considered as one of the most effective carriers to control and prolong drug delivery. Nanocarriers with different structures are promising agents in cancer therapy. In preclinical studies, they have been loaded with several antitumor drugs such as cisplatin, doxorubicin, paclitaxel, etc. For drug delivery systems including nanocarriers, an active and passive targeting should be included. Moreover, the most commonly used targeting ligands include antibodies, peptides, small molecules and aptamer. Among which, antibodies are one of the best choices for nanocarriers, which have high binding affinity and specificity. There are many approaches used for conjugating antibodies to therapeutic nanocarriers, such as periodate oxidation, carbodiimide, maleimide, and heterofunctional linkers, etc. Antibody-nanocarrier conjugate is a promising strategy for targeted therapies in various diseases.
References
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