Hypoxia-Responsive Tetrameric Supramolecular Polypeptide Nanoprodrugs for Combination Therapy.
Yue DingWei YuRongkai ShenXiangqin ZhengHui ZhengYong YaoYuehua ZhangChang DuHuan YiPublished in: Advanced healthcare materials (2023)
Despite the intense progress of photodynamic and chemotherapy, however they cannot prevent solid tumor invasion, metastasis and relapse, along with inferior efficacy and severe side effect. The hypoxia-responsive nanoprodrugs integrating photodynamic functions have been highly sought to address the above-mentioned problems and overcome the tumor hypoxia-reduced efficacy. Herein, a hypoxia-responsive tetrameric supramolecular polypeptide nanoprodrug (SPN-TAPP-PCB4) was constructed from the self-assembly of tetrameric porphyrin-central poly(L-lysine-azobenzene-chlorambucil) (TAPP-(PLL-Azo-CB)4) and an anionic water-soluble [2]biphenyl-extended-pillar[6]arene (AWBpP6) via the synergy of hydrophobic, π-π stacking, and host-guest interactions. Upon laser irradiation, the central TAPP could convert oxygen to generate single oxygen (1O2) to kill tumor cells. Furthermore, under the acidic and PDT-aggravated hypoxia tumor cell microenvironment, SPN-TAPP-PCB4 was rapidly disassembled, and then efficiently released activated CB through the hypoxic-responsive cleavage of azobenzene linkages. Both in vitro and in vivo biological studies showcased synergistic cancer-killing actions between photodynamic therapy (PDT) and chemotherapy (CT) with negligible toxicity. Consequently, this supramolecular polypeptide nanoprodrug offers an effective strategy to design a hypoxia-responsive nanoprodrug for potential combo PDT-CT transition. This article is protected by copyright. All rights reserved.
Keyphrases
- photodynamic therapy
- water soluble
- cancer therapy
- endothelial cells
- combination therapy
- drug delivery
- fluorescence imaging
- computed tomography
- mental health
- image quality
- magnetic resonance imaging
- energy transfer
- oxidative stress
- squamous cell carcinoma
- radiation therapy
- wastewater treatment
- early onset
- ionic liquid
- pet ct
- cell migration
- drug induced
- rectal cancer