Conjugated Polymer Nanogel Binding Anticancer Drug through Hydrogen Bonds for Sustainable Drug Delivery

Hydrogen-bonded drug conjugation is highly expected as the next-generation smart therapeutic agent that remains stable in biological medium. A carrier design strategy of hydrogen-bonded drug conjugates as pendants in conjugated polymer nanogel is developed. The H-bond acceptor uracil-functionalized poly(p-phenylenevinylene) and 2, 6-diamino pyridine (H-bond donor)-functionalized doxorubicin (Dox-Py) are synthesized. Further, chemically cross-linked PPV-nanogel with hydrogen-bonded drug complex (PPV-NG/Dox-Py) is fabricated. The presence of triple-point hydrogen bonding in polymer complex as well as in nanogel network is confirmed by ¹H NMR and FT-IR. The hydrophobic microenvironment offered by conjugated polymers backbone stabilizes the hydrogen bonding in the nanogel network. PPV-nanogel/Dox-Py hydrogen-bonded conjugation facilitates higher drug-loading efficiency (82%) and cancer-cell-killing efficiency than encapsulated drug, indicating the superiority of the present design. Sustainable release of Dox-Py is achieved for several days in response to the redox intracellular and acidic environment inside the cancer cells. The proposed hydrogen bond conjugation strategy could provide a broad platform for developing high-value nanotherapeutics.