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Formulation and Delivery - Chemical

(M1230-01-02) Redox-Responsive Fattigated Nanoparticles Potentiate Lipid Accumulation and Controlled Doxorubicin Release for Boosting the Anti-Cancer Activity

Monday, October 21, 2024
12:30 PM – 1:30 PM MT

    Presenting Author(s)

  • HN

    Hai Van Ngo, PhD

    Postdoc Research Fellow
    Ajou University
    Suwon-si, Kyonggi-do, Republic of Korea

    • Main Author(s)

  • HN

    Hai Van Ngo, PhD

    Postdoc Research Fellow
    Ajou University
    Suwon-si, Kyonggi-do, Republic of Korea

    • Co-Author(s)

  • HN

    Hy Dinh Nguyen, MS

    Graduate student
    Ajou University
    Suwon-si, Kyonggi-do, Republic of Korea

  • SL

    Sang Min Lee, BS

    Graduate student
    Ajou University
    Suwon-si, Kyonggi-do, Republic of Korea

  • BK

    Bo Mi Kim, BS

    Graduate student
    Ajou University
    Suwon-si, Kyonggi-do, Republic of Korea

  • JP

    Ji-Min Park, BS

    Graduate student
    Ajou University
    Suwon-si, Kyonggi-do, Republic of Korea

  • EB

    Eun Jin Baek, BS

    Graduate student
    Ajou University
    Suwon-si, Kyonggi-do, Republic of Korea

  • BL

    Beom-Jin Lee, Ph.D.

    Professor
    Ajou University
    Suwon-si, Kyonggi-do, Republic of Korea

Purpose: To investigate a new carbohydrate-cystamine-oleic acid conjugate that could self-assemble into nanoparticles for encapsulating doxorubicin and imparting a redox-sensitive behavior for improved anti-cancer activity.

Methods: Cystamine (CYS) as a diamine linker was used to bridge the carboxylic groups of oleic acid (OA) and carbohydrate (HA) to form HA-CYS-OA conjugate (HOC) via a two-step reaction employing EDC/NHS coupling agents. Doxorubicin (DOX) was chosen to load into self-assembled HOC nanoparticles (DOX-HON) using sonoprecipitation method. The redox-responsive properties of blank HON and DOX-HON were evaluated, focusing on the disassembly of nanoparticles and drug release upon the presence of glutathione (GSH) as mimicking the reductive environment. Human normal fibroblasts (HFF-1) and human breast cancer cells (MCF-7)  were used to assess the selectivity indices (SI) of the anti-cancer activity of HOC and three DOX formulations (free DOX, DOX-HON, and Caelyx®).

Results: HOC demonstrated the ability to induce lipid accumulation and exhibit an anti-cancer effect with good selectivity index (SI = 1.7). The spherical morphology of HON remained stable in PBS (200-300 nm), but upon the treatment of 10 mM GSH, they increased in size and disassembled into irregular shapes due to the cleavage of disulfide bonds of HOC. Subsequently, DOX release from DOX-HON was significantly accelerated with approximately 45% and 90% of drug release after 6 h in response to 1 mM and 10 mM GSH media, respectively. Finally, the DOX-HON showed the superior selectivity (SI = 14.5) compared to free DOX and Caelyx®.

Conclusion: The redox-sensitivity of DOX-HON facilitated increased OA and DOX release in the reductive environment of cancer cells. A dual release of OA induced lipid accumulation, synergistically enhancing the anti-cancer activity. Collectively, HON appears to be a promising nanocarrier for improving the selective activity of chemotherapeutics.

Acknowledgements: This work was supported by a grant from the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (RS-2023-00208240), Republic of Korea.