Applied Chemistry for Engineering (공업화학)

The Korean Society of Industrial and Engineering Chemistry (한국공업화학회)
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Reactive Oxygen Species-degradable Hydrogel System for Effective Localized Photodynamic Therapy of Cancer

효과적인 종양 국소 부위 광역학 치료를 위한 활성 산소 분해성 하이드로겔

  • Ji In Lee (Graduate School of Energy Science and Technology, Chungnam National University) ;
  • Jongseon Choi (Graduate School of Energy Science and Technology, Chungnam National University) ;
  • So Yeon Kim (Graduate School of Energy Science and Technology, Chungnam National University)
  • 이지인 (충남대학교 에너지과학기술대학원) ;
  • 최종선 (충남대학교 에너지과학기술대학원) ;
  • 김소연 (충남대학교 에너지과학기술대학원)
  • Received : 2024.10.02
  • Accepted : 2024.10.25
  • Published : 2024.12.10
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Abstract

Recently, photodynamic therapy (PDT), one of the phototherapy methods, requires various therapeutic strategies to overcome the limitations of photosensitizer (PS) with hydrophobicity and non-selectivity. In this study, we designed a reactive oxygen species (ROS)-degradable hydrogel based on a thermo-sensitive polymer (poly(N-isopropylacrylamide)) containing PS (PNIPAM-C/PS) for effective localized PDT of cancer. We successfully synthesized a crosslinker with a thioketal bond degradable by ROS, and a thermo-sensitive injectable hydrogel was fabricated using the ROS-responsive crosslinker. PNIPAM-based injectable hydrogel was able to be injected through syringe needles at room temperature, but it was converted to gel phase through phase transition at 37 ℃ above lower critical solution temperature (LCST). PNIPAM-C/PS injectable hydrogel prepared using ROS-degradable crosslinker was selectively degraded in ROS environment and showed good biocompatibility before and after degradation. When irradiated with a 670 nm laser, PNIPAM-C/PS injectable hydrogel showed high phototoxicity by ROS generation. The PNIPAM-C/PS injectable hydrogel with selective degradation properties and excellent phototoxicity by ROS could be promising materials for effective localized PDT of cancer.

광 치료 요법 중 하나인 광역학 치료(photodynamic therapy)는 소수성 및 낮은 선택성을 갖는 광증감제의 한계를 극복하기 위한 다양한 치료 전략이 요구되고 있다. 본 연구에서는 효과적인 종양 국소 부위의 광역학 치료를 위해 광증감제가 담지된 온도 감응성 고분자 poly(N-isopropylacrylamide) 기반의 주입형 하이드로겔(injectable hydrogel) (PNIPAM-C/PS)을 개발하였다. 반응성 산소종(reactive oxygen species, ROS)에 의한 분해성을 갖는 티오케탈 결합을 포함한 가교제를 성공적으로 합성하였고, 이를 사용하여 제조된 하이드로겔은 실온에서 주사기를 통해 주입이 가능한 반면 37 ℃ 이상의 온도에서는 상전이를 통해 gel phase로 전환될 수 있었다. PNIPAM-C/PS 주입형 하이드로겔은 ROS 환경에서 선택적 분해성 및 분해 전/후 높은 생체 안전성을 보였다. 또한, 670 nm 파장의 광원을 조사하였을 때, 생성된 ROS에 의해 높은 세포 독성을 나타내었다. ROS에 의한 선택적 분해성 및 우수한 광독성을 갖는 PNIPAM-C/PS 주입형 하이드로겔은 효과적인 종양 국소 부위의 광역학 치료 분야에 다양하게 응용 가능할 것이라 여겨진다.

Keywords

Acknowledgement

이 논문은 정부(교육부)의 재원으로 한국연구재단의 지원을 받아 수행된 연구임 (No. 2021R1I1A2059144).

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