Supramolecular grafting of stimuli-responsive, carrier-free, self-deliverable nanoparticles of camptothecin and antisense DNA for combination cancer therapy

Carrier-free delivery of therapeutically relevant small molecules and functional oligonucleotides is extremely challenging and is one of the major hurdles in cancer therapy. Herein, we report a non-covalent approach for the design of self-deliverable nanoparticles of camptothecin and antisense DNA....

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Bibliographic Details
Published in:New journal of chemistry 2022-09, Vol.46 (35), p.16813-1682
Main Authors: Perumal, Devanathan, Kalathil, Jemshiya, Krishna, Jithu, Raj, Gowtham, Harikrishnan, Kaloor S, Uthpala, M. L, Gupta, Ria, Varghese, Reji
Format: Article
Language:English
Subjects:
Anticancer properties
Cancer therapies
Drugs
Nanoparticles
Oligonucleotides
Self-assembly
Stimuli
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Summary:Carrier-free delivery of therapeutically relevant small molecules and functional oligonucleotides is extremely challenging and is one of the major hurdles in cancer therapy. Herein, we report a non-covalent approach for the design of self-deliverable nanoparticles of camptothecin and antisense DNA. Our strategy relies on the electrostatic attraction between the cationic ammonium group of the camptothecin prodrug and the negatively charged backbone of antisense DNA as the key interaction. Self-assembly between the camptothecin prodrug and antisense DNA results in the formation of a supramolecular amphiphile, wherein the hydrophobic camptothecin is electrostatically tethered along the phosphate backbone of DNA. The subsequent amphiphilicity-driven self-assembly of the supramolecular amphiphile leads to the formation of stimuli-responsive prodrug nanoparticles. The most notable structural feature of prodrug nanoparticles is the presence of redox-responsive disulfide bonds, which permits thiol-triggered disassembly of the nanoparticles and the release of active drugs. By exploring the high concentration of GSH inside the cancerous cells, we in vitro demonstrate the carrier-free self-delivery of two anticancer drugs simultaneously. Excellent anticancer activity is observed due to the combined therapeutic effect of camptothecin and antisense DNA. A supramolecular approach for the crafting of self-deliverable nanoparticles of antisense DNA and camptothecin for combination cancer therapy is reported.
ISSN:1144-0546
1369-9261
DOI:10.1039/d2nj01952c