Automated Modular Synthesis of Aptamer–Drug Conjugates for Targeted Drug Delivery

Abstract

Aptamer–drug conjugates (ApDCs) are promising targeted drug delivery systems for reducing toxicity while increasing the efficacy of chemotherapy. However, current ApDC technologies suffer from problems caused by the complicated preparation and low controllability of drug–aptamer conjugation. To solve such problems, we have designed and synthesized a therapeutic module for solid phase synthesis, which is a phosphoramdite containing an anticancer drug moiety and a photocleavable linker. Using this module, we have realized automated and modular synthesis of ApDCs, and multiple drugs were efficiently incorporated into ApDCs at predesigned positions. The ApDCs not only recognize target cancer cells specifically, but also release drugs in a photocontrollable manner. We demonstrated the potential of automated and modular ApDC technology for applications in targeted cancer therapy.

Smart Cu(II)-aptamer complexes based gold nanoplatform for tumor micro-environment triggered programmable intracellular prodrug release, photodynamic treatment and aggregation induced photothermal therapy of hepatocellular carcinoma

“…It is a promising targeting element for drug delivery applications due to its small size, synthetic accessibility, thermal stability, specific binding and easy with chemical modifications 23, 24. Meanwhile, it not only could serve as a targeting element for nano-carrier design, but also could serve as drug carrier itself for controlled drug release (e.g.…”

Nuclease-resistant synthetic drug-DNA adducts: programmable drug-DNA conjugation for targeted anticancer drug delivery

“…30,31 However, noncovalent conjugation typically requires specific DNA sequences or modification with additional sequences for drug conjugation; yet current solid-phase DNA synthesis technology can only synthesize DNA of limited lengths. Likewise, covalent drug-DNA conjugation typically relies on DNA modification with reactive groups, and complicated organic synthesis with low yield.…”

“…Likewise, covalent drug-DNA conjugation typically relies on DNA modification with reactive groups, and complicated organic synthesis with low yield. 30,31 Moreover, when systemically administered in a physiological environment, DNA complexes could be degraded or dissociated by ubiquitous nucleases, dilution to low concentrations by blood and strong shear forces. 32 To prevent nuclease degradation, current strategies again rely on either chemical modification (for example, phosphorothioate linkages and 2'-O-methyl) 32 or the use of other nanomaterials.…”

Photoactivation of Butyric Acid from 6‐Aminobenzocoumarin Cages

“…upon irradiation, [4] ii) photoactive polymers for encapsulation of guest molecules and as drug delivery systems, [5,6] iii) photoactive nanoparticle carriers for therapeutic agent release, iv) targeted cancer therapies, in nanomedicine and diagnostics, [7][8][9][10] v) photoactive hydrogels with tunable mechanical properties as scaffolds for cell culture and tissue regeneration, [11,12] vi) light controlled antibacterial agents for selecting specific bacterial strains from microbial mixtures for healthcare and microbiology research, [13] vii) agents enabling photocontrolled synthesis of aptamer-drug conjugates for selective tissue recognition in targeted cancer therapy, [14] viii) photolabile linkers for solid phase synthesis of peptides and heterocycles, [15,16] and ix) agents to enable the uncaging of bioactive molecules such as antibiotics, oligonucleotides and neurotransmitters from photolabile precursors.…”