Synthesis and in vitro biological evaluation of lipophilic cation conjugated photosensitizers for targeting mitochondria

Rajaputra, Pallavi; Nkepang, Gregory; Watley, Ryan; You, Youngjae

doi:10.1016/j.bmc.2012.11.032

Cited by 51 publications

(56 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both of them are increased in the case of BMPCP-4P 2 , but cellular uptake is smaller for TMPCP-4P than for TMPCP. These findings indicate that amphiphilic character is better for the cellular uptake (Ezzeddine et al 2013) but other factors like charge distribution (Rajaputra et al 2013) size and geometry of the compound could also influence the interactions with the cell.…”

Section: Discussionmentioning

confidence: 93%

See 1 more Smart Citation

Oligo- and polypeptide conjugates of cationic porphyrins: binding, cellular uptake, and cellular localization

et al. 2017

View full text Add to dashboard Cite

Recently we have characterized the DNA and nucleoprotein (NP) binding of bis(4-Nmethylpyridyl)-15,20-di(4-carboxyphenyl)porphyrin (BMPCP) and meso-tri(4-Nmethylpyridyl)-mono(4-carboxyphenyl)porphyrin (TMPCP) and their tetra-peptide conjugates (BMPCP-4P 2 and TMPCP-4P, respectively). In this work we investigated the interaction of TMPCP conjugated to the tetra-peptide branches of branched chain polymeric polypeptide with poly-L-lysine backbone (AK) with DNA or NP using spectroscopic methods.Analysis of absorption spectra revealed the external binding, but no intercalation of TMPCP-AK to DNA. There was no evidence for the interaction between TMPCP-AK and encapsidated DNA. Furthermore, we examined the cellular uptake of BMPCP and TMPCP and their tetra-or polypeptide conjugates by flow cytometry and analyzed how charge, size and structure of the compounds affect their incorporation. In comparison, liposomal association constants of these derivatives were determined. BMPCP-4P 2 accumulated the most, and porphyrins with two positive charges (BMPCP and BMPCP-4P 2 ) showed better accumulation than the tri-cationic TMPCP or TMPCP-4P.Cellular uptake of polycationic TMPCP-AK was significantly lower than that of the free or tetra-peptide conjugated derivatives. The sub-cellular localization of all the five compounds was investigated in co-localization studies by confocal microscopy with special attention to their nuclear localization. Neither free nor conjugated BMPCP or TMPCP were co-localized with nuclear marker. Instead, these derivatives showed co-localization with lysosomal and mitochondrial fluorescent probes. TMPCP-AK conjugate had different localization pattern appearing mainly in mitochondria and cytoplasmic vesicles.Our results may contribute to the further design of DNA targeting porphyrin based constructs.

show abstract

Section: Discussionmentioning

confidence: 93%

“…Several authors showed before that the cellular uptake of cationic porphyrins varies with the number and distribution of positive charges, the size and the hydrophilic/lipophilic character of the compounds Rajaputra et al 2013;Ezzeddine 2013). …”

Section: Discussionmentioning

confidence: 99%

Oligo- and polypeptide conjugates of cationic porphyrins: binding, cellular uptake, and cellular localization

et al. 2017

View full text Add to dashboard Cite

show abstract

“…All three cationic conjugates were significantly more PDT-efficient in mouse colon cancer cells (Colon 26), because of improved cellular uptake in comparison to unconjugated CMP-OH, but, b a s e d o n f l u o r e s c e n c e m i c r o s c o p y, s e l e c t i v e mitochondria-targeting in human breast cancer cells (MCF-7) has been suggested only for CMP-Rh. A conjugate with two tPP groups was somewhat less efficient in targeting mitochondria, and the conjugate with only one tPP group was not evident in mitochondria, but both conjugates were more phototoxic than CMP-Rh, especially CMP-(tPP) which showed the highest cellular uptake (Rajaputra et al 2012). Surprisingly, mitochondrial localisation could not be proven for a series of derivatives of 5,10,15,20-tetrakis-(4-N-methylpyridyl)-porphine (TMPyP4), with alkyl chains of various lengths instead of a methyl group, despite bearing positive charges.…”

Section: Mitochondrial Targetingmentioning

confidence: 96%

Porphyrin-based cationic amphiphilic photosensitisers as potential anticancer, antimicrobial and immunosuppressive agents

2017

View full text Add to dashboard Cite

Photodynamic therapy (PDT) combines a photosensitiser, light and molecular oxygen to induce oxidative stress that can be used to kill pathogens, cancer cells and other highly proliferative cells. There is a growing number of clinically approved photosensitisers and applications of PDT, whose main advantages include the possibility of selective targeting, localised action and stimulation of the immune responses. Further improvements and broader use of PDT could be accomplished by designing new photosensitisers with increased selectivity and bioavailability. Porphyrin-based photosensitisers with amphiphilic properties, bearing one or more positive charges, are an effective tool in PDT against cancers, microbial infections and, most recently, autoimmune skin disorders. The aim of the review is to present some of the recent examples of the applications and research that employ this specific group of photosensitisers. Furthermore, we will highlight the link between their structural characteristics and PDT efficiency, which will be helpful as guidelines for rational design and evaluation of new PSs.

show abstract

“…[39][40][41][42] As the therapeutic effect only occurs at sites with the presence of both PSs and light irradiation, the side effects toward surrounding health tissues are minimized. However, due to the short lifetime (<0.04 µs) and limited radius of action (<0.02 µm) of singlet oxygen, [ 12,[43][44][45] the therapeutic effect of PDT is largely affected by the localization of PSs inside cells. Selective targeting toward the most critical subcellular organelles is therefore highly desirable to achieve high anticancer response.…”

Section: Introductionmentioning

confidence: 99%

“…[51][52][53][54] For example, porphyrin derivatives have been widely reported in mitochondria-targeted PDT. [ 12,52,55,56 ] However, due to the large hydrophobicity of most PSs, they naturally aggregate in aqueous media or when they are accumulated in mitochondria with limited spaces. The aggregation-caused quenching (ACQ) effect of traditional PSs often leads to quenched fl uorescence as well as reduced ROS generation, [57][58][59] which largely compromised the effi ciencies of PDT.…”

Section: Introductionmentioning

confidence: 99%

Cellular and Mitochondrial Dual‐Targeted Organic Dots with Aggregation‐Induced Emission Characteristics for Image‐Guided Photodynamic Therapy

Feng

Qin

et al. 2015

Adv Healthcare Materials

View full text Add to dashboard Cite

Targeted delivery of drugs toward mitochondria of specific cancer cells dramatically improves therapy efficiencies especially for photodynamic therapy (PDT), as reactive oxygen species (ROS) are short in lifetime and small in radius of action. Different from chemical modification, nanotechnology has been serving as a simple and nonchemical approach to deliver drugs to cells of interest or specific organelles, such as mitochondria, but there have been limited examples of dual-targeted delivery for both cells and mitochondria. Here, cellular and mitochondrial dual-targeted organic dots for image-guided PDT are reported based on a fluorogen with aggregation-induced emission (AIEgen) characteristics. The AIEgen possesses enhanced red fluorescence and efficient ROS production in aggregated states. The AIE dot surfaces are functionalized with folate and triphenylphosphine, which can selectively internalize into folate-receptor (FR) positive cancer cells, and subsequently accumulate at mitochondria. The direct ROS generation at mitochondria sites is found to depolarize mitochondrial membrane, affect cell migration, and lead to cell apoptosis and death with enhanced PDT effects as compared to ROS generated randomly in cytoplasm. This report demonstrates a simple and general nanocarrier approach for cellular and mitochondrial dual-targeted PDT, which opens new opportunities for dual-targeted delivery and therapy.

show abstract

Synthesis and in vitro biological evaluation of lipophilic cation conjugated photosensitizers for targeting mitochondria

Cited by 51 publications

References 42 publications

Oligo- and polypeptide conjugates of cationic porphyrins: binding, cellular uptake, and cellular localization

Oligo- and polypeptide conjugates of cationic porphyrins: binding, cellular uptake, and cellular localization

Porphyrin-based cationic amphiphilic photosensitisers as potential anticancer, antimicrobial and immunosuppressive agents

Cellular and Mitochondrial Dual‐Targeted Organic Dots with Aggregation‐Induced Emission Characteristics for Image‐Guided Photodynamic Therapy

Contact Info

Product

Resources

About