4.8 Article

NIR-II Light Leveraged Dual Drug Synthesis for Orthotopic Combination Therapy

Journal

ACS NANO
Volume -, Issue -, Pages -

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsnano.2c06314

Keywords

bioorthogonal chemistry; second near-infrared; enhanced reaction efficiency; dual prodrug activation; orthotopic tumor

Funding

  1. National Key R&D Program of China [2019YFA0709202]
  2. Natural Science Foundation of China [21820102009, 91856205, 22237006]
  3. Key Program of Frontier of Sciences [CAS QYZDJ-SSW-SLH052]

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In this study, a NIR-II light promoted integrated catalyst is designed to accelerate the reaction efficiency and achieve a dual bioorthogonal reaction for combination therapy. The results show that this integrated catalyst exhibits significant anti-tumor activity in vivo.
Pd-catalyzed bioorthogonal bond cleavage reactions are widely used and frequently reported. It is circumscribed by low reaction efficiency, which may encumber the therapeutic outcome when applied to physiological environments. Herein, an NIR-II light promoted integrated catalyst (CuS@PDA/Pd) (PDA -polydopamine) is designed to accelerate the reaction efficiency and achieve a dual bioorthogonal reaction for combination therapy. As NIR-II light can penetrate deeply into tissue, the Pd-mediated cleavage reaction can be promoted both in vitro and in vivo by the photothermal properties of CuS, beneficial to orthotopic 4T1 tumor treatment. In addition, CuS also catalyzes the synthesis of active resveratrol analogs by the CuAAC reaction. These simultaneously produced anticancer agents result in enhanced antitumor cytotoxicity in comparison to the single treatments. This is a fascinating study to devise an integrated catalyst boosted by NIR-II light for dual bioorthogonal catalysis, which may provide the impetus for efficient bioorthogonal combination therapy in vivo.

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