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Targeted co-delivery of FOXM1 aptamer and DOX by nucleolin aptamer-functionalized pH-responsive biocompatible nanodelivery system to enhance therapeutic efficacy against breast cancer: in vitro and in vivo

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Abstract

Targeted nanodelivery systems offer a promising approach to cancer treatment, including the most common cancer in women, breast cancer. In this study, a targeted, pH-responsive, and biocompatible nanodelivery system based on nucleolin aptamer-functionalized biogenic titanium dioxide nanoparticles (TNP) was developed for targeted co-delivery of FOXM1 aptamer and doxorubicin (DOX) to improve breast cancer therapy. The developed targeted nanodelivery system exhibited almost spherical morphology with 124.89 ± 12.97 nm in diameter and zeta potential value of − 23.78 ± 3.66 mV. FOXM1 aptamer and DOX were loaded into the nanodelivery system with an efficiency of 100% and 97%, respectively. Moreover, the targeted nanodelivery system demonstrated excellent stability in serum and a pH-responsive sustained drug release profile over a period of 240 h following Higuchi kinetic and Fickian diffusion mechanism. The in vitro cytotoxicity experiments demonstrated that the targeted nanodelivery system provided selective internalization and strong growth inhibition effects of about 45 and 51% against nucleolin-positive 4T1 and MCF-7 breast cancer cell lines. It is noteworthy that these phenomena were not observed in nucleolin-negative cells (CHO). The preclinical studies revealed that a single-dose intravenous injection of the targeted nanodelivery system into 4T1-bearing mice inhibited tumor growth by 1.7- and 1.4-fold more efficiently than the free drug and the non-targeted nanodelivery system, respectively. Our results suggested that the developed innovative targeted pH-responsive biocompatible nanodelivery system could serve as a prospectively potential platform to improve breast cancer treatment.

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The datasets generated and/or analyzed during the current study are available from the corresponding authors on reasonable request.

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Funding

This work was supported by the Ferdowsi University of Mashhad (grant number: 56126).

Ferdowsi University of Mashhad,56126,Mina Masoudi

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Authors and Affiliations

  1. Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran

    Mina Masoudi & Gholamreza Hashemitabar

  2. Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Seyed Mohammad Taghdisi

  3. Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Seyed Mohammad Taghdisi

  4. Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Khalil Abnous

  5. Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Khalil Abnous

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  1. Mina Masoudi
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  2. Seyed Mohammad Taghdisi
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  3. Gholamreza Hashemitabar
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  4. Khalil Abnous
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Contributions

MM: conceptualization, visualization, validation, investigation, writing-original draft, and writing—review and editing; SMT: conceptualization, validation, and writing—review and editing; GH: supervision and writing—review and editing; and KA: supervision and writing—review and editing.

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Correspondence to Gholamreza Hashemitabar or Khalil Abnous.

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Masoudi, M., Taghdisi, S.M., Hashemitabar, G. et al. Targeted co-delivery of FOXM1 aptamer and DOX by nucleolin aptamer-functionalized pH-responsive biocompatible nanodelivery system to enhance therapeutic efficacy against breast cancer: in vitro and in vivo. Drug Deliv. and Transl. Res. 14, 1535–1550 (2024). https://doi.org/10.1007/s13346-023-01495-5

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