Photodynamic diagnosis and photodynamic therapy of colorectal cancer <i>in vitro</i> and <i>in vivo</i>

Simelane, Nokuphila Winifred Nompumelelo; Kruger, Cherie Ann; Abrahamse, Heidi

doi:10.1039/d0ra08617g

Cited by 35 publications

(34 citation statements)

References 97 publications

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Section: Introductionmentioning

confidence: 99%

“…Photodynamic diagnosis (PDD) and photodynamic therapy (PDT) are light-based modalities that can be utilized for the early diagnosis and treatment of CRC [4]. These modalities make use of a photosensitive compound, known as a photosensitizer (PS) [4]. PSs can passively localize in cancer cells and, upon the absorption of visible light at a specific wavelength, they can either exhibit fluorescence (for PDD) and/or convert surrounding cellular oxygen into reactive cytotoxic species, which, in turn, induce cell death [4].…”

Section: Introductionmentioning

confidence: 99%

“…These modalities make use of a photosensitive compound, known as a photosensitizer (PS) [4]. PSs can passively localize in cancer cells and, upon the absorption of visible light at a specific wavelength, they can either exhibit fluorescence (for PDD) and/or convert surrounding cellular oxygen into reactive cytotoxic species, which, in turn, induce cell death [4]. PDD is a non-damaging diagnostic modality that utilizes fluorescence, produced by blue light (340-540 nm) [3].…”

Section: Introductionmentioning

confidence: 99%

“…This is due to their characteristic intense Q-band of peak absorption, observed within the 583, 634, and 674 nm visible infra-red region [11]. Furthermore, the 674 nm wavelength of activation for ZnPcS 4 PSs can achieve deep-seated tissue penetration and offers more effective PDT treatment outcomes [11,12]. Furthermore, ZnPcS 4 PSs also possesses a Soret band peak around 330 to 350 nm (visible blue light) of excitation [10].…”

Section: Introductionmentioning

confidence: 99%

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Targeted Nanoparticle Photodynamic Diagnosis and Therapy of Colorectal Cancer

Simelane

Kruger

Abrahamse

2021

IJMS

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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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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Targeted Nanoparticle Photodynamic Diagnosis and Therapy of Colorectal Cancer

Simelane

Kruger

Abrahamse

2021

IJMS

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“…The method that meets these criteria and can be used in personalized therapy of CRC is PDT [15]. One of the most common agents used in PDT of colorectal with satisfactory results cancer is 5-aminolevulinic acid (ALA), a precursor of Protoporphyrin IX (PpIX) [14,16].…”

Section: Introductionmentioning

confidence: 99%

Biotin-Containing Third Generation Glucoheptoamidated Polyamidoamine Dendrimer for 5-Aminolevulinic Acid Delivery System

Kaczorowska

Malinga-Drozd

Kałas

et al. 2021

IJMS

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Polyamidoamine PAMAM dendrimer generation 3 (G3) was modified by attachment of biotin via amide bond and glucoheptoamidated by addition of α-D-glucoheptono-1,4-lacton to obtain a series of conjugates with a variable number of biotin residues. The composition of conjugates was determined by detailed 1-D and 2-D NMR spectroscopy to reveal the number of biotin residues, which were 1, 2, 4, 6, or 8, while the number of glucoheptoamide residues substituted most of the remaining primary amine groups of PAMAM G3. The conjugates were then used as host molecules to encapsulate the 5-aminolevulinic acid. The solubility of 5-aminolevulinic acid increased twice in the presence of the 5-mM guest in water. The interaction between host and guest was accompanied by deprotonation of the carboxylic group of 5-aminolevulinic acid and proton transfer into internal ternary nitrogen atoms of the guest as evidenced by a characteristic chemical shift of resonances in the 1H NMR spectrum of associates. The guest molecules were most likely encapsulated inside inner shell voids of the host. The number of guest molecules depended on the number of biotin residues of the host, which was 15 for non-biotin-containing glucoheptoamidated G3 down to 6 for glucoheptoamidated G3 with 8 biotin residues on the host surface. The encapsulates were not cytotoxic against Caco-2 cells up to 200-µM concentration in the dark. All encapsulates were able to deliver 5-aminolevulinic acid to cells but aqueous encapsulates were more active in this regard. Simultaneously, the reactive oxygen species were detected by staining with H2DCFDA in Caco-2 cells incubated with encapsulates. The amount of PpIX was sufficient for induction of reactive oxygen species upon 30-s illumination with a 655-nm laser beam.

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