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  • [Biomaterials.] Beyond hydrophilic polymers in amphiphilic polymer-based self-assembled NanoCarriers: Small hydrophilic carboxylate-capped disulfide drug delivery system and its multifunctionality and multispatial targetability

    가톨릭대 / 최연수, 조하나, 강한창*, 이혜숙*

  • 출처
    Biomaterials.
  • 등재일
    2022 Jan
  • 저널이슈번호
    280:121307. doi: 10.1016/j.biomaterials.2021.121307. Epub 2021 Dec 6.
  • 내용

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    Abstract
    Due to increasing safety and intracellular delivery concerns about hydrophilic polymers in amphiphilic polymer-based nanoparticles (NPs), this study investigates small hydrophilic molecule-stabilized NPs for effective intracellular delivery with multiorganelle targetability and dual responsiveness to acidic pH/glutathione (GSH). In the construction of small hydrophilic molecule-stabilized NP (MSPCL-NP), the A-B-A-type amphiphilic polymer (MSPCL-P) is composed of two short hydrophilic carboxylate-capped disulfide derivatives (A) that replace hydrophilic polymers and assist in providing colloidal stability and preventing antibody (e.g., at least anti-PEG antibody)-mediated specific interactions and complement activation in the plasma and a hydrophobic multiple disulfide-containing poly(ε-caprolactone) block (B) that carries hydrophobic drugs. The carboxylates on the surface of MSPCL-NP target the acidic extratumoral/endolysosomal milieu by sensing and buffering acidic pH values, and the hydrophobic carboxylic acids improve adsorptive endocytosis and effective endosomal escape. Multiple disulfide linkages selectively target cytosolic GSH, resulting in rapid drug release from the destroyed MSPCL-NP via the cleavage of disulfide bonds in MSPCL-P. Doxorubicin (DOX)-loaded NP (DOX@MSPCL-NP) exerts strong effects on killing cells in vitro and inhibits tumor growth in HCT116 xenograft tumor-bearing mice. In conclusion, the multifunctionality and multispatial targetability of MSPCL-NP might effectively overcome various sequential drug delivery hurdles, ranging from blood circulation to drug release. Furthermore, the introduction of small hydrophilic molecules represents a potential strategy to make self-assembled NPs without the use of hydrophilic polymers.

     

     

    Affiliations

    Yeon Su Choi  1 , Hana Cho  1 , Won-Gu Choi  1 , Sung Su Lee  1 , Kang Moo Huh  2 , Min Suk Shim  3 , In Suh Park  4 , Yong-Yeon Cho  1 , Joo Young Lee  1 , Hye Suk Lee  5 , Han Chang Kang  6
    1 Department of Pharmacy, College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 14662, Republic of Korea.
    2 Department of Polymer Science and Engineering, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Republic of Korea.
    3 Division of Bioengineering, Incheon National University, 119 Academy-ro, Yeonsu-gu, Incheon, 22012, Republic of Korea.
    4 Department of Pathology, Inha University Hospital, 27 Inhang-ro, Jung-gu, Incheon, 22332, Republic of Korea.
    5 Department of Pharmacy, College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 14662, Republic of Korea. Electronic address: sianalee@catholic.ac.kr.
    6 Department of Pharmacy, College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 14662, Republic of Korea. Electronic address: hckang@catholic.ac.kr.

  • 키워드
    Amphiphilic; Antibody-mediated adverse effect; Carboxylate-capped disulfide; Colloidal stability; Cytosolic targeting; pH targeting.
  • 편집위원

    기존의 양친매성 고분자 기반 나노입자는 친수성 고분자에 대한 안전성 및 세포내 전달에 대한 우려가 있어왔다. 이 논문은 기존 나노입자에 비해 더 효과적인 세포내 전달을 위해, 친수성 고분자를 사용하지 않고 작은 친수성 분자를 도입한 small hydrophilic molecule-stabilized NP (MSPCL-NP)의 개발을 보여주고 있다. 결과적으로, 세포 및 마우스 실험을 통하여 보다 나은 항암효과를 보여주며, MSPCL-NP의 더 효과적인 약물 전달 가능성을 제시하고 있다.

    2022-03-07 17:55:12

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