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  • [J Control Release.] Hydroxyapatite-binding albumin nanoclusters for enhancing bone tumor chemotherapy

    서울대, 충남대 / 강내원, 김대덕*, 이재영*

  • 출처
    J Control Release.
  • 등재일
    2022 Feb
  • 저널이슈번호
    342:111-121. doi: 10.1016/j.jconrel.2021.12.039. Epub 2022 Jan 3.
  • 내용

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    Abstract
    Hydroxyapatite-binding albumin nanoclusters (NCs) were developed for improving the anticancer agent accumulation in bone tumors. Human serum albumin (HSA) was decorated with alendronate (AD), and doxorubicin (DOX)-loaded NCs (HSA-AD/DOX) were fabricated via the ball-milling technology, an innovative nano-fabrication method by which more than 90% of the secondary structures of albumin can be preserved. The targeting ability of NCs was confirmed using a novel in vitro bone cancer model, wherein hydroxyapatite and collagen, the major components of the bone matrix representing the highly mineralized bone tumor microenvironment, were co-cultured with HOS/MNNG, a human osteosarcoma cell line. The binding affinity of HSA-AD/DOX to hydroxyapatite was evaluated based on the DOX binding efficiency. HSA-AD/DOX showed a 5.04-fold higher affinity than HSA/DOX. The enhanced distribution of HSA-AD/DOX to bone tumors was verified using a newly developed mouse model bearing HOS/MNNG tumors with hydroxyapatite beads. HSA-AD/DOX led to a 52.0% increase in tumor accumulation compared to that of the unmodified HSA/DOX. This is mainly due to the hydroxyapatite-binding affinity of the AD moiety, which is supported by histological analyses performed on the dissected tumors. Furthermore, HSA-AD/DOX changed the protein expression patterns of the tumors, implying the enhanced apoptotic process. Overall, the targeting ability of HSA-AD/DOX are effectively translated into improved therapeutic efficacy in bone tumor-xenografted mice, suggesting that the developed NCs are a promising delivery system for bone tumor treatment.

     

     

    Affiliations

    Nae-Won Kang  1 , Jae-Young Lee  2 , Dae-Duk Kim  3
    1 College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea.
    2 College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea. Electronic address: jaeyoung@cnu.ac.kr.
    3 College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea. Electronic address: ddkim@snu.ac.kr.

  • 키워드
    Alendronate; Bone tumors; Human serum albumin; Hydroxyapatite; Nanoclusters.
  • 편집위원

    본 논문은 골종양에서의 항암제 효과를 개선하기 위해 개발한Hydroxyapatite-binding albumin nanoclusters (NCs)에 대한 연구를 다루고 있다. 인혈청알부민(HSA)에 alendronate(AD)을 도입하여 골 종양 미세환경을 나타내는 골기질의 주요 성분인 hydroxyapatite에 HSA가 잘 결합하도록 하였고, 이에 doxorubicin(DOX) 항암제까지까지 도입한 NC(HSA-AD/DOX)를 개발하였다. 결과적으로 in vitro/in vivo 실험을 통해 NC(HSA-AD/DOX)의 골 종양 표적화 능력으로 개선된 치료 효과를 보였으며, 앞으로의 골 종양 치료 연구에 도움이 될 것으로 기대된다.

    2022-04-05 13:58:46

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