Key result
Disulfiram and doxorubicin co-loaded nanoparticles strongly inhibited in vitro metastasis of 4T1 cells, with a wound healing rate of 36.50% and a migration rate of 18.39%, and suppressed in vivo metastasis.
Why the study?
Metastasis remains a major obstacle in breast cancer treatment, motivating the development of enzyme/pH dual stimuli-responsive nanoparticles co-delivering disulfiram and doxorubicin.
Enzyme/pH dual stimuli-responsive nanoparticles co-delivering disulfiram and doxorubicin effectively inhibit breast cancer metastasis in preclinical models.
Answers are grounded in this paper and cite their sources.
Should not change practice; hypothesis-generating for stimuli-responsive nanoparticles in breast cancer metastasis.
OBJECTIVES: Metastasis is still one of the main obstacles in the treatment of breast cancer. This study aimed to develop disulfiram (DSF) and doxorubicin (DOX) co-loaded nanoparticles (DSF-DOX NPs) with enzyme/pH dual stimuli-responsive characteristics to inhibit breast cancer metastasis. METHODS: DSF-DOX NPs were prepared using the amphiphilic poly(ε-caprolactone)-b-poly(L-glutamic acid)-g-methoxy poly(ethylene glycol) (PCL-b-PGlu-g-mPEG) copolymer by a classical dialysis method. In vitro release tests, in vitro cytotoxicity assay, and anti-metastasis studies were conducted to evaluate pH/enzyme sensitivity and therapeutic effect of DSF-DOX NPs. RESULTS: The specific pH and enzyme stimuli-responsiveness of DSF-DO NPs can be attributed to the transformation of secondary structure and the degradation of amide bonds in the PGlu segment, respectively. This accelerated drug release significantly increased the cytotoxicity to 4T1 cells. Compared with the control group, the DSF-DOX NPs showed a strong inhibition of in vitro metastasis with a wound healing rate of 36.50% and a migration rate of 18.39%. Impressively, in vivo anti-metastasis results indicated that the metastasis of 4T1 cells was almost completely suppressed by DSF-DOX NPs. CONCLUSION: DSF-DOX NPs with controllable tumor site delivery of DOX and DSF were a prospectively potential strategy for metastatic breast cancer treatment.
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Xiao et al. (2023) studied Breast cancer lung metastasis. Disulfiram (DSF) and doxorubicin (DOX) co-loaded nanoparticles (DSF-DOX NPs) vs. Control group was evaluated on In vitro metastasis (wound healing rate and migration rate). Disulfiram and doxorubicin co-loaded nanoparticles strongly inhibited in vitro metastasis of 4T1 cells, with a wound healing rate of 36.50% and a migration rate of 18.39%, and suppressed in vivo metastasis.
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