Targeted Nanoparticle Photodynamic Diagnosis and Therapy of Colorectal Cancer

被引:17
|
作者
Simelane, Nokuphila Winifred Nompumelelo [1 ]
Kruger, Cherie Ann [1 ]
Abrahamse, Heidi [1 ]
机构
[1] Univ Johannesburg, Laser Res Ctr, Fac Hlth Sci, POB 17011, ZA-2028 Doornfontein, South Africa
基金
新加坡国家研究基金会;
关键词
colorectal cancer; photodynamic diagnosis; photodynamic therapy; zinc phthalocyanine; nanoparticle; tumor targeting; PHOTOSENSITIZERS; CONJUGATION; PHTHALOCYANINE; ANTIBODIES;
D O I
10.3390/ijms22189779
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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, ZnPcS4-AuNP-S-PEG5000-NH2-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.
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页数:22
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