Targeted Nanoparticle Photodynamic Diagnosis and Therapy of Colorectal Cancer

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.

Zinc Phthalocyanine Tetrasulfonate-Loaded Ag@mSiO2 Nanoparticles for Active Targeted Photodynamic Therapy of Colorectal Cancer

“…Whereas the cells received various concentrations of the active NC followed by irradiation resulting in cell viability inhibition with increasing doses of ZnPcS 4 . Additionally, under the IC 50 value of ZnPcS 4 (0.125 µM) with a light dose of 10 J/cm 2 , ZnPcS 4 /Ag@mSiO 2 -FA could reduce the cell viability to 38.0% ± 4.2*** relative to ZnPcS 4 /Ag@mSiO 2 with 67.0% ± 7.4* viability and the IC 50 for FA loaded NC was found to be 0.0625 µM which was 2-fold less than free ZnPcS 4 PS (0.125 µM) in the previous study (Simelane et al, 2021). The higher cell viability in passive ZnPcS 4 /Ag@mSiO 2 NC compared to free ZnPcS 4 might be attributed to the faster entry of free PS into the cells (Wang Y. et al, 2019).…”

“…The intracellular localization of the NCs was determined based on the described protocol (Montaseri et al, 2021;Simelane et al, 2021). Briefly, Caco-2 cells were seeded on sterilized coverslips at a density of 3.0×10 5 cells in 1 ml media and cultured for 24 hr.…”

“…replaced by fresh media containing NCs at different concentrations as previously established in our group (Simelane et al, 2021). The experimental groups were divided into two subgroups, with and without 674 nm laser irradiation with a semiconductor diode laser (10 J/cm 2 , 9.5 mW/cm 2 , 17 min).…”

Fluorescent Polymers Conspectus

“…As well as sensing materials [ 55 ], CPs have been intensively researched for biosensing and bioimaging applications due to their great light-harvesting capacity, outstanding photostability, and easily surface-modifiable features [ 122 , 123 , 124 ]. For instance, photodynamic therapy (PDT) [ 125 , 126 ] has become an important cancer treatment that uses reactive oxygen species (ROS) (such 1 O 2 and hydroxyl radicals) created by exposing photosensitizers (PS) to light irradiation in an oxygen-rich environment to destroy cancer cells. Zhang and coworkers [ 127 ] prepared a positively charged water-soluble polythiophene polymer (PT0, Figure 16 ).…”

Receptor Guanylyl Cyclase C and Cyclic GMP in Health and Disease: Perspectives and Therapeutic Opportunities

“…Other emerging GC-C-directed modalities for the early diagnosis and treatment of colorectal cancer include photodynamic diagnosis (PDD) and photodynamic therapy (PDT), which are light-based approaches that can be used for the early diagnosis and treatment of colorectal cancer ( 104 ). Recently, PDD and PDT approaches involving zinc phthalocyanine as a photosensitizer bound to a polyethylene glycol-gold nanoparticle that could be directly delivered to a colorectal cancer site using a specific antibody against GC-C were developed and tested in cell culture studies ( 105 , 106 ).…”