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

• Published in: Materials today advances 2022-06, Vol.14, p.100218, Article 100218
• Main Authors: Lee, H., Dey, D.K., Kim, K., Kim, S., Kim, E., Kang, S.C., Bajpai, V.K., Huh, Y.S.
• Format: Article
• Language: English
• Subjects: Drug delivery system; Hypoxia; In vivo xenograft model; Photodynamic therapy; Spheroid; Tumor microenvironment (TME)
• ISSN: 2590-0498; 2590-0498
• DOI: 10.1016/j.mtadv.2022.100218

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 (-NN-) 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.