Abstract
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.
Highlights
Colorectal cancer (CRC) was identified as the fourth deadliest cause of cancer-associated fatalities at the global level [1]
The optimal concentration dose (ICD50) for ZnPcS4 PS photodynamic therapy (PDT) dose response were performed in order to determine the required concentration of ZnPcS4 PS that was needed within the final Bioactive Nanoconjugate (BNC) for effective Photodynamic diagnosis (PDD) or PDT outcomes
This study successfully fabricated a bioactive nanoconjugate, ZnPcS4AuNP-S-PEG5000-NH2-Anti-guanylyl cyclase C (GCC) monoclonal antibodies (mAbs) (BNC), based upon a PEGylated AuNPs, which was multi-functionalized with a fluorescent PDT metalated ZnPcS4 PS, and specific antiGCC targeting mAbs, to overcome in vitro CRC PDD and PDT challenges
Summary
Colorectal cancer (CRC) was identified as the fourth deadliest cause of cancer-associated fatalities at the global level [1]. Despite the tremendous advancements in currently used diagnostic and treatment options, the overall impact on survival rate is limited, especially when CRC is diagnosed at late advanced stages [1]. Colonoscopy and flexible sigmoidoscopies, some of the definitive diagnostic methods currently utilized, can yield a five year survival rate of around 90% within early localized stages of CRC [2]. These conventional diagnostic methods are invasive, nonspecific, and often too inaccurate to diagnose early stage CRC [2]. Some of the traditional first-line treatment strategies for CRC, such as surgery, radiotherapy, and chemotherapy, are invasive and induce severe unwanted side effects [2]. There is a strong need to investigate novel, highly-selective therapeutic modalities that are less invasive, can promote early diagnosis, and enhance treatment efficacy, while causing minimal systemic toxicity and side effects in healthy tissues as compared to conventional treatments [3]
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