Fluorescence properties of several chemotherapy drugs: doxorubicin, paclitaxel and bleomycin

Motlagh, Najmeh Sadat Hosseini; Parvin, Parviz; Ghasemi, Fatemeh; Atyabi, Fatemeh

doi:10.1364/boe.7.002400

Cited by 139 publications

(101 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…if the observed downregulation of ABCB1 expression after ROR1 inhibition correlated with a decrease in chemo drug efflux, we monitored doxorubicin in cells following ROR1 inhibition. Doxorubicin has intrinsic fluorescence 29 and can be monitored via confocal microscopy. We observed an increase in doxorubicin levels within cells 24 h after treatment, following ROR1 knockdown and Strc inhibition, when compared to control RNA and vehicle treatment groups ( Fig.…”

Section: Ror1 Inhibition Represses Doxorubicin Efflux From Cells To mentioning

confidence: 99%

ROR1 regulates chemoresistance in Breast Cancer via modulation of drug efflux pump ABCB1

Fultang

Illendula

Lin

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Chemoresistance is one of the leading causes of mortality in breast cancer (BC). Understanding the molecules regulating chemoresistance is critical in order to combat chemoresistant BC. Drug efflux pump ABCB1 is overexpressed in chemoresistant neoplasms where it effluxes various chemotherapeutic agents from cells. Because it is expressed in normal and cancerous cells alike, attempts at targeting ABCB1 directly have failed due to low specificity and disruption of normal tissue. A proposed method to inhibit ABCB1 is to target its cancer-specific, upstream regulators, mitigating damage to normal tissue. Few such cancer-specific upstream regulators have been described. Here we characterize ROR1 as an upstream regulator of ABCB1. ROR1 is highly expressed during development but not expressed in normal adult tissue. It is however highly expressed in several cancers. ROR1 is overexpressed in chemoresistant BC where it correlates with poor therapy response and tumor recurrence. Our data suggests, ROR1 inhibition sensitizes BC cells to chemo drugs. We also show ROR1 regulates ABCB1 stability and transcription via MAPK/ERK and p53. Validating our overall findings, inhibition of ROR1 directly correlated with decreased efflux of chemo-drugs from cells. Overall, our results highlight ROR1's potential as a therapeutic target for multidrug resistant malignancies. ROR1 knockdown potentiates DNA damage induced by chemo drugs.A mechanism of action common to both Pt-based and anthracycline chemotherapeutic agents is induction of DNA double stranded breaks leading to cell death 19 . We thus sought to investigate if ROR1 inhibition would promote chemo-induced DNA double strand breaks. We treated cells transfected with either ROR1 siRNA or control RNA, with Doxorubicin or Cisplatin, and monitored γH2a.x, a marker for DNA double strand breaks via immunofluorescence ( Fig. 3A, Supplementary Fig. 2). We observed potentiation of DNA double strand breaks induced by both drugs in cells where ROR1 was knocked down. γH2a.x foci counts were higher in the siROR1+ (Dox or Cis) groups compared to the siROR1-only and drug-only treatment groups (Fig. 3B). We similarly observed an increase in γH2a.x expression (mean fluorescence intensity) in Cis/Dox treated cells after ROR1 knockdown compared to the control group (Fig. 3C). Altogether, these data suggest ROR1 inhibition promotes chemo drug-induced DNA damage. Scientific RepoRtS |(2020) 10:1821 | https://doi.

show abstract

Section: Ror1 Inhibition Represses Doxorubicin Efflux From Cells To mentioning

confidence: 99%

ROR1 regulates chemoresistance in Breast Cancer via modulation of drug efflux pump ABCB1

Fultang

Illendula

Lin

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…The resulting blanked spectrum overlaid with PTX and FA spectra is shown in Figure c. The shoulder peak at 227 and 272 nm are characteristic peaks of PTX and FA, respectively, confirming the presence of both the molecules 8a,21. The amount of PTX and FA was quantified by using Beer's law, and the result shows the linear relationship between absorbance and concentration of PTX for the concentration range of 5–20 µg mL −1 (Figure S1a,b, Supporting Information); a linear relationship was also found between the absorbance and concentration of FA at the concentration range of 1.25–5 µg mL −1 (Figure S2b, Supporting Information); approximately 173 PTX molecules and 82 FA molecules per NP were detected.…”

Section: Resultsmentioning

confidence: 82%

Paclitaxel‐Loaded Iron Oxide Nanoparticles for Targeted Breast Cancer Therapy

Jeon

Lin

Stephen

et al. 2019

Advanced Therapeutics

View full text Add to dashboard Cite

Paclitaxel (PTX) is a potent drug for treating advanced solid carcinomas; however, its clinical utility is limited by its poor water solubility. Despite the promise of using nanoparticles to deliver hydrophobic PTX, achieving sufficient drug loading while maintaining small particle size and stability in biological media remains a challenge. Here, a PTX nanoparticle (NP) formulation with small size and great stability is presented that targets breast cancer cells and enables controlled release of PTX. This NP formulation (NP-PTX-FA) comprises a superparamagnetic iron oxide core coated with short-and long-chain polyethylene glycol: the former for conjugation of hydrophobic PTX and folic acid (FA), and the latter as an outer layer for improved hydrophilicity. The NP-PTX-FA has a uniform size distribution (averaging 28.2 ± 0.64 nm) and high drug loading capacity of 22.8 wt% (vs <10 wt% normally). NP-PTX-FA releases the drug under conditions mimicking the acidic intracellular pH of breast cancer cells and the FA conjugation leads to higher NP uptake by target cells, enhancing the cytotoxicity to target cells compared to free PTX. This NP formulation holds great promise to improve breast cancer therapy and potential to deliver other hydrophobic drugs for treating various cancer types.

show abstract

“…For the synthesis of fluorescently labelled nanogels (Nanogel Cy5 ), 2% of the reactive esters on the polymer were substituted with cyanine5-amine prior to crosslinking. We chose cyanine5 as a labelling agent because its fluorescence excitation and emission spectra do not, contrary to rhodamine and fluorescein, show overlap with the spectra of doxorubicin 52 .…”

Section: Resultsmentioning

confidence: 99%

pH-Sensitive Hydrazone-Linked Doxorubicin Nanogels via Polymeric-Activated Ester Scaffolds: Synthesis, Assembly, and In Vitro and In Vivo Evaluation in Tumor-Bearing Zebrafish

et al. 2018

View full text Add to dashboard Cite

Nanoparticle conjugation is a powerful method to reduce the side effects of anticancer agents such as doxorubicin by altering the pharmacokinetic profile of the drug.Nanoparticles can prolong circulation time and could also promote enhanced accumulation in tumors, either passively via the EPR effect or actively when decorated with targeting motifs. For the particular case of doxorubicin, hydrazone-based conjugation chemistry is popular, but commonly involves laborious chemical transformation steps 1 . Here we report on a straightforward route for the synthesis of hydrazine-based doxorubicin-polymer conjugates starting from a polymeric activated ester scaffold onto which doxorubicinreactive hydrazide moieties are introduced by simple treatment with hydrazine. Using block copolymers composed of hydrophobic reactive ester block we demonstrate a simple route to assemble core-crosslinked doxorubicin-loaded nanoparticles. The latter largely retain their bioactivity in vitro. In a zebrafish embryo ´pre-murine´ in vivo model we demonstrate a dramatic reduction in systemic toxicity of doxorubicin upon nanoparticle-conjugation and also demonstrate enhanced tumor accumulation and tumor growth reduction.

show abstract

Fluorescence properties of several chemotherapy drugs: doxorubicin, paclitaxel and bleomycin

Cited by 139 publications

References 18 publications

ROR1 regulates chemoresistance in Breast Cancer via modulation of drug efflux pump ABCB1

ROR1 regulates chemoresistance in Breast Cancer via modulation of drug efflux pump ABCB1

Paclitaxel‐Loaded Iron Oxide Nanoparticles for Targeted Breast Cancer Therapy

pH-Sensitive Hydrazone-Linked Doxorubicin Nanogels via Polymeric-Activated Ester Scaffolds: Synthesis, Assembly, and In Vitro and In Vivo Evaluation in Tumor-Bearing Zebrafish

Contact Info

Product

Resources

About