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Dual Bioluminescence Imaging of Tumor Progression and Angiogenesis
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Redox Dual-Responsive and O2‑Evolving Theranostic Nanosystem for Highly Selective Chemotherapy against Hypoxic Tumors

Huachao Chen1, Fei Li2, Yongrong Yao1

  • 1State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China.

Theranostics
|January 22, 2019
PubMed

Insights

This study introduces a novel dual-activatable theranostic nanosystem for targeted chemotherapy in hypoxic tumors. The system enables precise drug delivery and real-time monitoring of treatment efficacy using near-infrared fluorescence.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Activatable theranostic agents offer improved tumor selectivity by combining fluorescent reporters with masked chemotherapeutics activated by tumor-specific stimuli.
  • Hypoxic tumors present a challenge for conventional chemotherapy, necessitating targeted delivery systems.
  • Developing systems for in situ monitoring of drug release and therapeutic response is crucial for optimizing cancer treatment.

Purpose of the Study:

  • To develop a reactive oxygen species (ROS)/glutathione (GSH) dual-activatable and oxygen (O2)-evolving theranostic nanosystem for selective chemotherapy in hypoxic tumors.
  • To enable in situ fluorescence tracking of cancer chemotherapy using near-infrared (NIR) imaging.
  • To investigate the therapeutic efficacy and drug release mechanisms of the developed nanosystem.

Main Methods:

  • A novel theranostic agent (RA-S-S-Cy) was synthesized, comprising a disulfide linker, an NIR fluorophore, and the active anti-cancer drug RA-V.
  • The RA-S-S-Cy agent was encapsulated into c(RGDfK)-targeted poly(lactic-co-glycolic acid) (PLGA) nanoparticles along with catalase to create RA-S-S-Cy@PLGA NPs, designed for dual redox responsiveness and O2 evolution.
  • In vitro and in vivo studies were conducted to evaluate drug release, fluorescence tracking, and therapeutic outcomes in hypoxic tumor models.

Main Results:

  • The RA-S-S-Cy@PLGA NPs demonstrated cell-specific and redox dual-activatable release of the RA-V drug, leading to enhanced therapeutic effects.
  • The nanosystem successfully enabled in situ monitoring of drug release and chemotherapeutic efficacy through 'turn-on' NIR fluorescence.
  • Significant improvements in therapeutic outcomes were observed in vivo and in vitro due to targeted drug delivery and activation.

Conclusions:

  • RA-S-S-Cy@PLGA NPs represent efficient theranostic nanosystems for precise therapy against hypoxic tumors.
  • The developed system provides a valuable tool for understanding drug release mechanisms in real-time.
  • This approach holds promise for advancing targeted cancer chemotherapy and improving treatment monitoring.
Keywords:
ROS/GSH dual-activatablecancercyclopeptide RA-Vfluorescence imaginghypoxic tumortheranostic system

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