Hypoxia-responsive nanomedicine to overcome tumor microenvironment-mediated resistance to chemo-photodynamic therapy

H. Lee, D. K. Dey, K. Kim, S. Kim, E. Kim, S. C. Kang, V. K. Bajpai, Y. S. Huh

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


Hypoxia is a feature of solid tumors that greatly hinders cancer treatment. Here, we developed hypoxia-responsive nanoparticles (NPs) that selectively release chlorin e6 (Ce6) and paclitaxel (PTX) under hypoxic conditions. To prepare the hypoxia-responsive NPs, PTX-loaded HSA NPs (PHNPs) were functionalized with 4,4′-azodianiline (Azo) as a linker for the PHNPs and Ce6 (CA/PHNPs). The CA/PHNPs were then functionalized with RGD-conjugated poly(ethylene glycol) (RP/CA/PHNPs). The azo group (-N[dbnd]N-) present in Azo was reductively cleaved under hypoxic conditions to release Ce6 and PTX. The release of Ce6 due to azo cleavage under hypoxia resulted in a uniform distribution of Ce6 within HeLa cells and spheroids, enhancing antitumor activity even in a hypoxic environment. The RP/CA/PHNPs also showed excellent antitumor effects in a HeLa cell xenograft mouse model. Thus, this strategy for controlling the drug distribution within a hypoxic tumor microenvironment (TME) potentially represents a very effective strategy for the removal of solid tumors with a hypoxic TME by improving the efficiency of photodynamic therapy and chemotherapy.

Original languageEnglish
Article number100218
JournalMaterials Today Advances
Publication statusPublished - 2022 Jun
Externally publishedYes


  • Drug delivery system
  • Hypoxia
  • In vivo xenograft model
  • Photodynamic therapy
  • Spheroid
  • Tumor microenvironment (TME)

ASJC Scopus subject areas

  • Materials Science(all)
  • Mechanical Engineering


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