Hypoxia alleviating platinum(IV)/chlorin e6-based combination chemotherapeutic-photodynamic nanomedicine for oropharyngeal carcinoma

Hypoxia is an important pathological hallmark of the tumor microenvironment, associated with metabolic al-terations, cell proliferation, aggressiveness, metastasis, and therapy resistance in cancers. Hypoxia impedes the outcome of photodynamic therapy (PDT), which is largely dependent on molecular oxygen to generate cytotoxic 1O2. Here, a near-infrared light activatable, oxygen-generating nanomicellar PDT-chemotherapy system (mPPCPN Ms) constituted of amphiphilic mPEG-PLA, photosensitizer Ce6, and tetravalent platinum prodrug Pt (IV)-diazide was developed for oral squamous cell carcinoma. The polymer conjugate self-assemble to nanosize (115 +/- 2.35 nm) micelles, which, upon irradiation (660 nm laser), activated Ce6, and photodecomposed to produce cytotoxic Pt(II), azidyl radical, and molecular oxygen. The strategically fabricated PDT-chemotherapy produced a strong antitumor response in vitro using oral squamous cell carcinoma and in vivo in oral cancer-xenografted mouse models, revealing its significant potential in chemo-photodynamic combination therapy with the benefit of reversing hypoxia.

Automated summary

Hypoxia is a key characteristic of the tumor microenvironment and affects various aspects of cancer, including cell proliferation, metastasis, and therapy resistance. A nanomicellar system that generates oxygen through near-infrared light activation was developed for the treatment of oral squamous cell carcinoma. The system showed significant potential in chemo-photodynamic combination therapy, effectively reversing hypoxia in oral cancer models.