Photochemical Internalization of Tamoxifens Transported by a “Trojan‐Horse” Nanoconjugate into Breast‐Cancer Cell Lines

Theodossiou, Theodossis A.; Gonçalves, A. Ricardo; Yannakopoulou, Konstantina; Skarpen, Ellen; Berg, Kristian

doi:10.1002/anie.201500183

Cited by 59 publications

(44 citation statements)

References 29 publications

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“…Another approach consists the photochemical delivery of drugs through photochemical internalization (PCI), a modified form of PDT. PCI is actually a light-controlled drug-delivery alternative in which light activation enables spatiotemporal specificity and control of the intracellular drug release [131][132][133] . Moreover the potential of PCI to circumvent the resistance and increase the efficacy of a variety of anticancer agents, have been demonstrated in several tumor models including approaches to overcome PDTresistance in breast cancer cells [133,134] .…”

Section: Perspectivesmentioning

confidence: 99%

Photodynamic therapy in cancer treatment - an update review

Santos¹,

Almeida²,

Terra³

et al. 2019

JCMT

320

327

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Cancer remains a worldwide health problem, being the disease with the highest impact on global health. Even with all the recent technological improvements, recurrence and metastasis still are the main cause of death. Since photodynamic therapy (PDT) does not compromise other treatment options and presents reduced long-term morbidity when compared with chemotherapy or radiotherapy, it appears as a promising alternative treatment for controlling malignant diseases. In this review, we set out to perform a broad up-date on PDT in cancer research and treatment, discussing how this approach has been applied and what it could add to breast cancer therapy. We covered topics going from the photochemical mechanisms involved, the different cell death mechanisms being triggered by a myriad of photosensitizers up to the more recent-on-going clinical trials.Metastatic lesions are usually multiple and resistant to conventional therapies, jeopardizing successful surgical resection, chemo and radiation treatment [4] .Light has been known to provide a therapeutic potential for several thousands of years. Over 3000 years ago, since the Ancient, Indian and Chinese civilizations it has been used for the treatment of various diseases [5] mainly in combination with reactive chemicals, for example to treat conditions like vitiligo, psoriasis and skin cancer [6] . After 1895 with the discovery of the phototherapy, which rendered Niels Ryberg Finsen the Nobel prize in Physiology/Medicine in 1903 in recognition of his work on the treatment of diseases, and in particular on the treatment of lupus vulgaris by means of concentrated light rays, many studies with the use of light and chemicals emerged [7] .Photodynamic therapy (PDT) is currently being used as an alternative treatment for the control of malignant diseases [8][9][10] . It is based in the uptake of a photosensitizer (PS) molecule which, upon being excited by light in a determined wavelength, reacts with oxygen and generates oxidant species (radicals, singlet oxygen, triplet species) in target tissues, leading to cell death [11,12] . PDT cytotoxic properties have been established to be due to the oxidation of a large range of biomolecules in cells, including nucleic acids, lipids, and proteins, leading to severe alteration in cell signaling cascades or in gene expression regulation [13,14] . Like all the newly proposed treatments, there is still place for improvements and lots of resources have been invested in this field recently. In this review, we set out to perform a broad up-date on PDT and it implication in cancer research and treatment. We have covered topics going from the photochemical mechanisms involved, the different cell death mechanisms being triggered by a myriad of photosensitizers up to the more recent reported preclinical studies and on-going clinical trials. PHOTOCHEMICAL PRINCIPLES AND COMPONENTS OF PDTAs previously stated, PDT involves the photosensitized oxidation of biomolecules which can be separated in two mechanisms. In Type I, light energy passes from exc...

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Section: Perspectivesmentioning

confidence: 99%

Photodynamic therapy in cancer treatment - an update review

Santos¹,

Almeida²,

Terra³

et al. 2019

JCMT

320

327

View full text Add to dashboard Cite

show abstract

“…Light is especially attractive as a triggering modality because it can be applied remotely with high spatiotemporal precision, while light parameters such as wavelength, power density, and illumination time can be adjusted to control the release platform 35 . In recent years, enhanced cytoplasmic delivery of macromolecular compounds by photochemical disruption of the endolysosomal membrane, referred to as photochemical internalization (PCI), 36 has been actively investigated in the context of gene delivery, including siRNA, peptide nucleic acids (PNAs), and plasmid DNA (pDNA), 37 and pharmacotherapy 38, 39, 40, 41, 42. For example, Park et al 39 .…”

Section: Introductionmentioning

confidence: 99%

Light-Triggerable Liposomes for Enhanced Endolysosomal Escape and Gene Silencing in PC12 Cells

Chen

Deng

Goldys

2017

Molecular Therapy - Nucleic Acids

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Liposomes are an effective gene and/or drug delivery system, widely used in biomedical applications including gene therapy and chemotherapy. Here, we designed a photo-responsive liposome (lipVP) loaded with a photosensitizer verteporfin (VP). This photosensitizer is clinically approved for photodynamic therapy (PDT). LipVP was employed as a DNA carrier for pituitary adenylyl cyclase-activating polypeptide (PACAP) receptor 1 (PAC1R) gene knockdown in PC12 cells. This has been done by incorporating PAC1R antisense oligonucleotides inside the lipVP cavity. Cells that have taken up the lipVP were exposed to light from a UV light source. As a result of this exposure, reactive oxygen species (ROS) were generated from VP, destabilizing the endolysosomal membranes and enhancing the liposomal release of antisense DNA into the cytoplasm. Endolysosomal escape of DNA was documented at different time points based on quantitative analysis of colocalization between fluorescently labeled DNA and endosomes and lysosomes. The released antisense oligonucleotides were found to silence PAC1R mRNA. The efficiency of this photo-induced gene silencing was demonstrated by a 74% ± 5% decrease in PAC1R fluorescence intensity. Following the light-induced DNA transfer into cells, cell differentiation with exposure to two kinds of PACAP peptides was observed to determine the cell phenotypic change after PAC1R gene knockdown.

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“…Hydrophobic PSs also tend to remain longer in the patient’s body compared to hydrophilic PSs. These observations have caused PSs with amphiphilic properties through conjugation with water soluble or amphiphilic polymers or colloidal administrations to become attractive in PDT studies [43,44,45,46,47]. …”

Section: Ps Uptake and Selectivitymentioning

confidence: 99%

Developments in PDT Sensitizers for Increased Selectivity and Singlet Oxygen Production

2015

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Photodynamic therapy (PDT) is a minimally-invasive procedure that has been clinically approved for treating certain types of cancers. This procedure takes advantage of the cytotoxic activity of singlet oxygen (1O2) and other reactive oxygen species (ROS) produced by visible and NIR light irradiation of dye sensitizers following their accumulation in malignant cells. The main two concerns associated with certain clinically-used PDT sensitizers that have been influencing research in this arena are low selectivity toward malignant cells and low levels of 1O2 production in aqueous media. Solving the selectivity issue would compensate for photosensitizer concerns such as dark toxicity and aggregation in aqueous media. One main approach to enhancing dye selectivity involves taking advantage of key methods used in pharmaceutical drug delivery. This approach lies at the heart of the recent developments in PDT research and is a point of emphasis in the present review. Of particular interest has been the development of polymeric micelles as nanoparticles for delivering hydrophobic (lipophilic) and amphiphilic photosensitizers to the target cells. This review also covers methods employed to increase 1O2 production efficiency, including the design of two-photon absorbing sensitizers and triplet forming cyclometalated Ir(III) complexes.

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Photochemical Internalization of Tamoxifens Transported by a “Trojan‐Horse” Nanoconjugate into Breast‐Cancer Cell Lines

Cited by 59 publications

References 29 publications

Photodynamic therapy in cancer treatment - an update review

Photodynamic therapy in cancer treatment - an update review

Light-Triggerable Liposomes for Enhanced Endolysosomal Escape and Gene Silencing in PC12 Cells

Developments in PDT Sensitizers for Increased Selectivity and Singlet Oxygen Production

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