Photoactivated HPPH-Liposomal therapy for the treatment of HPV-Negative head and neck cancer. Oral Oncol 2023 Sep;144:106487
Date
07/10/2023Pubmed ID
37423200Pubmed Central ID
PMC10413333DOI
10.1016/j.oraloncology.2023.106487Scopus ID
2-s2.0-85164978149 (requires institutional sign-in at Scopus site) 2 CitationsAbstract
OBJECTIVES: Human Papillomavirus (HPV)-negative head and neck cancer (HNC) is an aggressive malignancy with a poor prognosis. To improve outcomes, we developed a novel liposomal targeting system embedded with 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH), a chlorin-based photosensitizer. Upon exposure to 660 nm light, HPPH phototriggering generates reactive oxygen species. The objective of this study was to evaluate biodistribution and test efficacy of HPPH-liposomal therapy in a patient-derived xenograft (PDX) model of chemoradioresistant HNC.
MATERIALS AND METHODS: PDX models were developed from two surgically resected HNCs (P033 and P038) recurrent after chemoradiation. HPPH-liposomes were created including trace amounts of DiR (Ex/Em 785/830 nm), a near infrared lipid probe. Liposomes were injected via tail vein into PDX models. Biodistribution was assessed at serial timepoints in tumor and end-organs through in vivo DiR fluorescence. To evaluate efficacy, tumors were treated with a cw-diode 660 nm laser (90 mW/cm2, 5 min). This experimental arm was compared to appropriate controls, including HPPH-liposomes without laser or vehicle with laser alone.
RESULTS: HPPH-liposomes delivered via tail vein exhibited selective tumor penetration, with a peak concentration at 4 h. No systemic toxicity was observed. Treatment with combined HPPH-liposomes and laser resulted in improved tumor control relative to either vehicle or laser alone. Histologically, this manifested as both increased cellular necrosis and decreased Ki-67 staining in the tumors treated with combined therapy.
CONCLUSIONS: These data demonstrate tumor-specific anti-neoplastic efficacy of HPPH-liposomal treatment for HNC. Importantly, this platform can be leveraged in future studies for targeted delivery of immunotherapies which can be packaged within HPPH-liposomes.
Author List
Zenga J, Awan M, Hadi Razeghi Kondelaji M, Hansen C, Shafiee S, Frei A, Foeckler J, Kuehn R, Bruening J, Massey B, Wong S, Joshi A, Himburg HAAuthors
Musaddiq J. Awan MD Assistant Professor in the Radiation Oncology department at Medical College of WisconsinJennifer D. Bruening MD Assistant Professor in the Otolaryngology department at Medical College of Wisconsin
Heather A. Himburg PhD Associate Professor in the Radiation Oncology department at Medical College of Wisconsin
Amit Joshi PhD Professor in the Biomedical Engineering department at Medical College of Wisconsin
Joseph Zenga MD Assistant Professor in the Otolaryngology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Head and Neck NeoplasmsHumans
Liposomes
Papillomavirus Infections
Photochemotherapy
Photosensitizing Agents
Tissue Distribution
