Open Access

Pharmacokinetic evaluation and antitumor potency of liposomal nanoparticle encapsulated cisplatin targeted to CD24‑positive cells in ovarian cancer

  • Authors:
    • Keisuke Ashihara
    • Yoshito Terai
    • Tomohito Tanaka
    • Yoshimichi Tanaka
    • Satoe Fujiwara
    • Kazuya Maeda
    • Satoshi Tunetoh
    • Hiroshi Sasaki
    • Masami Hayashi
    • Masahide Ohmichi
  • View Affiliations

  • Published online on: January 9, 2020     https://doi.org/10.3892/ol.2020.11279
  • Pages: 1872-1880
  • Copyright: © Ashihara et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

CD24, which is upregulated in several human malignancies, is related to Epithelial‑mesenchymal‑transition (EMT) and has characteristics of cancer stem‑like cells, especially in cisplatin‑resistant ovarian carcinoma cells. Drug delivery systems represent a promising therapeutic approach for diseases with treatment resistance, and the present study investigated a novel CD24‑targeted drug delivery system for advanced ovarian carcinoma. We produced liposomal cisplatin with a red fluorescent substance ‑ cyanine 5.5 (GL‑CDDP‑Cy5.5). In order to target CD24‑positive cells, an anti‑CD24 monoclonal antibody was modified to the above drug (CD24‑GL‑CDDP‑Cy5.5). Specific uptake of CD24‑GL‑CDDP‑Cy5.5 was confirmed using a therapeutically resistant ovarian cancer cell line, Caov‑3 cells. Antitumor effects of CD24‑GL‑CDDP‑Cy5.5 were then evaluated in Caov‑3 xenograft mice. CD24‑GL‑CDDP‑Cy5.5 showed more specific uptake by flow cytometry than GL‑CDDP‑Cy5.5. In xenograft mice, GL‑CDDP‑Cy5.5 and CD24‑GL‑CDDP‑Cy5.5 treatment had significantly higher platinum concentration in disseminated tumor cells than cisplatin (P<0.05). Moreover, CD24‑GL‑CDDP‑Cy5.5 suppressed tumor growth and prolonged survival time compared with other treatments. Median survival times of the control, cisplatin, GL‑CDDP‑Cy5.5 and CD24‑GL‑CDDP‑Cy5.5 groups were 37, 36, 46 and 54 days after inoculation, respectively. Immunohistochemical analysis showed that CD24‑GL‑CDDP‑Cy5.5 treatment, compared with GL‑CDDP‑Cy5.5, decreased the number of CD24‑positive cells and suppressed the EMT phenomenon significantly (P<0.05). The present study demonstrated that CD24‑GL‑CDDP‑Cy5.5, compared with other treatments, improved therapeutic efficacy. The present results suggested the potential for targeting anticancer therapeutics for CD24‑positive cells to prevent disease progression.

Related Articles

Journal Cover

March 2020
Volume 19 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
APA
Ashihara, K., Terai, Y., Tanaka, T., Tanaka, Y., Fujiwara, S., Maeda, K. ... Ohmichi, M. (2020). Pharmacokinetic evaluation and antitumor potency of liposomal nanoparticle encapsulated cisplatin targeted to CD24‑positive cells in ovarian cancer. Oncology Letters, 19, 1872-1880. https://doi.org/10.3892/ol.2020.11279
MLA
Ashihara, K., Terai, Y., Tanaka, T., Tanaka, Y., Fujiwara, S., Maeda, K., Tunetoh, S., Sasaki, H., Hayashi, M., Ohmichi, M."Pharmacokinetic evaluation and antitumor potency of liposomal nanoparticle encapsulated cisplatin targeted to CD24‑positive cells in ovarian cancer". Oncology Letters 19.3 (2020): 1872-1880.
Chicago
Ashihara, K., Terai, Y., Tanaka, T., Tanaka, Y., Fujiwara, S., Maeda, K., Tunetoh, S., Sasaki, H., Hayashi, M., Ohmichi, M."Pharmacokinetic evaluation and antitumor potency of liposomal nanoparticle encapsulated cisplatin targeted to CD24‑positive cells in ovarian cancer". Oncology Letters 19, no. 3 (2020): 1872-1880. https://doi.org/10.3892/ol.2020.11279