PEGylated Purpurin 18 with Improved Solubility: Potent Compounds for Photodynamic Therapy of Cancer

Abstract

Purpurin 18 derivatives with a polyethylene glycol (PEG) linker were synthesized as novel photosensitizers (PSs) with the goal of using them in photodynamic therapy (PDT) for cancer. These compounds, derived from a second-generation PS, exhibit absorption at long wavelengths; considerable singlet oxygen generation and, in contrast to purpurin 18, have higher hydrophilicity due to decreased logP. Together, these properties make them potentially ideal PSs. To verify this, we screened the developed compounds for cell uptake, intracellular localization, antitumor activity and induced cell death type. All of the tested compounds were taken up into cancer cells of various origin and localized in organelles known to be important PDT targets, specifically, mitochondria and the endoplasmic reticulum. The incorporation of a zinc ion and PEGylation significantly enhanced the photosensitizing efficacy, decreasing IC50 (half maximal inhibitory compound concentration) in HeLa cells by up to 170 times compared with the parental purpurin 18. At effective PDT concentrations, the predominant type of induced cell death was apoptosis. Overall, our results show that the PEGylated derivatives presented have significant potential as novel PSs with substantially augmented phototoxicity for application in the PDT of cervical, prostate, pancreatic and breast cancer.

Purpurin binding interacts with LHPP protein that inhibits PI3K/AKT phosphorylation and induces apoptosis in colon cancer cells HCT‐116

“…Preceding study stated that PEGylated purpurin at submicromolar concentrations, induces apoptosis with negligible necrosis. [ 57 ] Consequently, for the first time, we exhibited that purpurin‐enhanced LHPP could initiate apoptosis in HCT‐116 colon cancer cells, and also delay tumor development. Present results authenticate that HCT‐116 cells were categorized by two stainings, EtBr as well as AO, in a time‐dependent manner after purpurin treatment.…”

Purpurin: A natural anthraquinone with multifaceted pharmacological activities

“…The attachment of short PEG3 moieties does not hinder purpurin photodynamic efficiency; in fact, it enhanced it by an aspect of at least two. Besides, PEGylated derivatives of purpurin have enhanced hydrophilicity concerning the parental compound (Hoober, Sery, & Yamamoto, 1988; Pavlickova et al, 2019). Thus, purpurin in the non‐excited state shows significant potential in cancer chemoprevention, and excited states have prospective in killing tumors or cancer cells.…”

Viral Nanoparticle System: An Effective Platform for Photodynamic Therapy

“…Following the study of porphyrins, most studies have turned to a class of photodynamically active natural molecules, such as chlorophyll (CpD) and its derivatives [ 45 , 46 , 47 ], and some dyes that can be used as potential photosensitizers. Such molecules can be easily obtained from natural resources [ 48 ].…”

“…As an important degradation product of chlorophyll-a, purpurin 18 and its derivative (with a polyethylene glycol (PEG) linker) were synthesized as novel photosensitizers (PSs). PEGylated derivatives have higher hydrophilicity, can significantly enhance phototoxicity, and can be used in the PDT of cervical cancer, prostate cancer, pancreatic cancer, and breast cancer [ 47 ]. Similarly, the phototoxicity effect of NT–pheophorbide (NT–Pba), a conjugate composed of red luminescent pheophorbide-a and nandrolone (NT), is more pronounced than the original pheophorbide-a [ 49 ].…”