Tumor cell death in orthotopic breast cancer model by NanoALA: a novel perspective on photodynamic therapy in oncology

Nanomedicine ◽  
2020 ◽  
Vol 15 (10) ◽  
pp. 1019-1036
Author(s):  
Laise R de Andrade ◽  
Antonio C Tedesco ◽  
Fernando L Primo ◽  
Gabriel R Farias ◽  
Jaqueline R da Silva ◽  
...  

Aim: Nano-5-aminolevulic acid (NanoALA)-mediated photodynamic therapy (PDT), an oil-in-water polymeric nanoemulsion of ALA, was evaluated in a murine model of breast cancer. Materials & methods: Analysis of ALA-derived protoporphyrin IX production and acute toxicity test, biocompatibility and treatment efficacy, and long-term effect of NanoALA-PDT on tumor progression were performed. Results: The nanoformulation favored the prodrug uptake by tumor cells in a shorter time (1.5 h). As a result, the adverse effects were negligible and the response rates for primary mammary tumor control were significantly improved. Tumor progression was slower after NanoALA-PDT treatment, providing longer survival. Conclusion: NanoALA is a good proactive drug candidate for PDT against cancer potentially applied as adjuvant/neoadjuvant intervention strategy for breast cancer.

2020 ◽  
Vol 3 (7) ◽  
pp. 2000022 ◽  
Author(s):  
Zachary K. Lyles ◽  
Mubin Tarannum ◽  
Cayli Mena ◽  
Natalia M. Inada ◽  
Vanderlei S. Bagnato ◽  
...  

2021 ◽  
Vol 9 (1) ◽  
pp. 221-237
Author(s):  
Zhiqiang Zhang ◽  
Anning Li ◽  
Xingqi Min ◽  
Qunqun Zhang ◽  
Jun Yang ◽  
...  

A temperature-sensitive hydrogel encapsulating tegafur and protoporphyrin IX dimers could be delivered intratumorally for synergetic chemotherapy and photodynamic therapy.


Oncogene ◽  
2021 ◽  
Author(s):  
Vida Vafaizadeh ◽  
David Buechel ◽  
Natalia Rubinstein ◽  
Ravi K. R. Kalathur ◽  
Lorenzo Bazzani ◽  
...  

AbstractCanonical Wnt/β-catenin signaling is an established regulator of cellular state and its critical contributions to tumor initiation, malignant tumor progression and metastasis formation have been demonstrated in various cancer types. Here, we investigated how the binding of β-catenin to the transcriptional coactivators B-cell CLL/lymphoma 9 (Bcl9) and Bcl9-Like (Bcl9L) affected mammary gland carcinogenesis in the MMTV-PyMT transgenic mouse model of metastatic breast cancer. Conditional knockout of both Bcl9 and Bcl9L resulted into tumor cell death. In contrast, disrupting the interaction of Bcl9/Bcl9L with β-catenin, either by deletion of their HD2 domains or by a point mutation in the N-terminal domain of β-catenin (D164A), diminished primary tumor growth and tumor cell proliferation and reduced tumor cell invasion and lung metastasis. In comparison, the disruption of HD1 domain-mediated binding of Bcl9/Bcl9L to Pygopus had only moderate effects. Interestingly, interfering with the β-catenin-Bcl9/Bcl9L-Pygo chain of adapters only partially impaired the transcriptional response of mammary tumor cells to Wnt3a and TGFβ treatments. Together, the results indicate that Bcl9/Bcl9L modulate but are not critically required for canonical Wnt signaling in its contribution to breast cancer growth and malignant progression, a notion consistent with the “just-right” hypothesis of Wnt-driven tumor progression.


2019 ◽  
Vol 6 (3) ◽  
pp. 362-372 ◽  
Author(s):  
Xiao Wang ◽  
Li Li ◽  
Kun Zhang ◽  
Zhen Han ◽  
Zhijian Ding ◽  
...  

The novel sensitizer S-Porphin sodium can generate ROS by radiation with a long wavelength to cause tumor cell death.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1375
Author(s):  
Hanieh Montaseri ◽  
Cherie Ann Kruger ◽  
Heidi Abrahamse

Photodynamic therapy (PDT) has been investigated as an effective, non-invasive, and alternative tumor-ablative therapy that uses photosensitizers (PSs) and safe irradiation light in the presence of oxygen to generate reactive oxygen species (ROS) to kill malignant cancer cells. However, the off-target activation of the PSs can hinder effective PDT. Therefore, an advanced drug delivery system is required to selectively deliver the PS to the therapeutic region only and reduce off-target side effects in cancer treatment. The integration of laser-initiated PDT with nanotechnology has provided new opportunities in cancer therapy. In this study, plasmonic bimetallic nanoparticles (NPs) were prepared for the targeted PDT (TPDT) of in vitro cultured MCF-7 breast cancer cells. The NPs were functionalized with PEG through Au–thiol linkage to enhance their biocompatibility and subsequently attached to the PS precursor 5-aminolevulinic acid via electrostatic interactions. In order to enhance specific targeting, anti-HER-2 antibodies (Ab) were decorated onto the surface of the nanoconjugate (NC) to fabricate a 5-ALA/Au–Ag-PEG-Ab NC. In vitro studies showed that the synthesized NC can enter MCF-7 cells and localize in the cytoplasm to metabolize 5-ALA to protoporphyrin IX (PpIX). Upon light irradiation, PpIX can efficiently produce ROS for the PDT treatment of MCF-7. Cellular viability studies showed a decrease from 49.8% ± 5.6 ** to 13.8% ± 2.0 *** for free 5-ALA versus the NC, respectively, under equivalent concentrations of the PS (0.5 mM, IC50). These results suggest that the active targeted NC platform has an improved PDT effect on MCF-7 breast cancer cells.


2006 ◽  
Vol 82 (6) ◽  
pp. 1638 ◽  
Author(s):  
Ingrid A. Boere ◽  
Dominic J. Robinson ◽  
Henriette S. de Bruijn ◽  
Jolanda Kluin ◽  
Hugo W. Tilanus ◽  
...  

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