Targeted Nanoparticle Photodynamic Diagnosis and Therapy of Colorectal Cancer

• Published in: International journal of molecular sciences Vol. 22; no. 18; p. 9779
• Main Authors: Simelane, Nokuphila Winifred Nompumelelo, Kruger, Cherie Ann, Abrahamse, Heidi
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10.09.2021; MDPI
• Subjects: Accumulation; Antineoplastic Agents - pharmacology; Apoptosis; Biological activity; Biomarkers; Cancer; Cancer therapies; Cell death; Cell Line, Tumor; Cell Proliferation - drug effects; Chemotherapy; Clinical outcomes; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - immunology; Colorectal Neoplasms - pathology; Colorectal Neoplasms - therapy; Cytotoxicity; Diagnosis; Drug dosages; Fatalities; Fluorescence; Gold; Gold - chemistry; Humans; Immunoconjugates - chemistry; Immunoconjugates - immunology; Immunoconjugates - pharmacology; Immunotherapy; Indoles - chemistry; Indoles - pharmacology; Light irradiation; Localization; Medical research; Metal Nanoparticles - chemistry; Metal Nanoparticles - therapeutic use; Monoclonal antibodies; nanoparticle; Nanoparticles; Organometallic Compounds - chemistry; Organometallic Compounds - pharmacology; Photochemotherapy; photodynamic diagnosis; Photodynamic therapy; Polyethylene glycol; Reactive Oxygen Species - metabolism; Spectrum analysis; tumor targeting; Tumors; zinc phthalocyanine; zinc phthalocyanine; nanoparticle; tumor targeting; colorectal cancer; photodynamic diagnosis; photodynamic therapy
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22189779

Colorectal cancer (CRC) is an aggressive cancer that remains a challenge to diagnose and treat. Photodynamic diagnosis (PDD) and therapy (PDT) are novel alternative techniques, which can enhance early diagnosis, as well as elicit tumor cell death. This is accomplished through photosensitizer (PS) mediated fluorescence and cytotoxic reactive oxygen species activation upon laser light irradiation excitation at specific low and high range wavelengths, respectively. However, the lack of PS target tumor tissue specificity often hampers these techniques. This study successfully fabricated a bioactive nanoconjugate, ZnPcS -AuNP-S-PEG5000-NH -Anti-GCC mAb (BNC), based upon a polyethylene glycol-gold nanoparticle, which was multi-functionalized with a fluorescent PDT metalated zinc phthalocyanine PS, and specific anti-GCC targeting antibodies, to overcome CRC PDD and PDT challenges. The BNC was found to be stable and showed selectively improved subcellular accumulation within targeted CRC for improved PDD and PDT outcomes in comparison to healthy in vitro cultured cells. Additionally, the BNC reported significantly higher late apoptotic PDT-induced CRC cell death rates (34% ***) when compared to PDT PS administration alone (15% *). These results indicated that the improved PDD and PDT outcomes were due to the specific PS accumulation in CRC cells through nanoparticle carriage and bioactive anti-GCC targeting.