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Delivery of bortezomib with nanoparticles for basal-like triple-negative breast cancer therapy
Song Shen1, Xiao-Jiao Du1, Jing Liu1
1The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui 230027, PR China.
Abstract:
Basal-like triple negative breast cancer (TNBC) has received particular clinical interest due to its high frequency, poor baseline prognosis and lack of effective clinical therapy. Bortezomib, which was the first proteasome inhibitor approved for the treatment of multiple myeloma, has been proven to be worth investigating for this subtype of breast cancer. In our study, the amphiphilic copolymer poly(ethylene glycol)-block-poly(d,l-lactide) (PEG-b-PLA) was utilized as an excellent delivery carrier of bortezomib (BTZ) to overcome its clinical limitations including low water solubility and unstable properties. Bortezomib encapsulated nanoparticles (NPBTZ) can efficiently deliver the drug into both CSCs (cancer stem cells) and non-CSCs, resulting in proliferation inhibition and apoptosis induction. Remarkably, NPBTZ can more effectively affect the stemness of CSCs compared with free BTZ. Administration of this drug delivery system can markedly prolong the bortezomib circulation half-life and augment the enrichment of drugs in tumor tissue, then enhance the suppression of tumor growth, suggesting the therapeutic promise of NPBTZ delivery in basal-like TNBC therapy.
Insights
This study developed novel nanoparticles encapsulating bortezomib (NPBTZ) for treating triple-negative breast cancer (TNBC). NPBTZ enhances drug delivery, improves efficacy against cancer stem cells, and shows therapeutic promise for TNBC.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Basal-like triple-negative breast cancer (TNBC) presents significant clinical challenges due to its aggressive nature and limited treatment options.
- Bortezomib (BTZ), a proteasome inhibitor, shows potential for TNBC but faces limitations like poor solubility and stability.
- Cancer stem cells (CSCs) are implicated in TNBC's resistance and recurrence, necessitating targeted therapeutic strategies.
Purpose of the Study:
- To develop and evaluate poly(ethylene glycol)-block-poly(d,l-lactide) (PEG-b-PLA) nanoparticles for enhanced delivery of bortezomib (BTZ) in basal-like TNBC.
- To investigate the efficacy of bortezomib-encapsulated nanoparticles (NPBTZ) in targeting both cancer stem cells (CSCs) and non-CSCs.
- To assess the impact of NPBTZ on CSC stemness, drug pharmacokinetics, and tumor growth suppression.
Main Methods:
- Synthesis of amphiphilic copolymer poly(ethylene glycol)-block-poly(d,l-lactide) (PEG-b-PLA) as a drug delivery vehicle.
- Encapsulation of bortezomib (BTZ) into PEG-b-PLA nanoparticles to form NPBTZ.
- In vitro evaluation of NPBTZ's cellular uptake, proliferation inhibition, and apoptosis induction in CSCs and non-CSCs.
- In vivo assessment of NPBTZ's effects on drug circulation half-life, tumor tissue enrichment, and tumor growth suppression.
Main Results:
- NPBTZ demonstrated efficient delivery of bortezomib into both CSCs and non-CSCs, leading to significant proliferation inhibition and apoptosis.
- NPBTZ exhibited superior efficacy in targeting CSC stemness compared to free bortezomib.
- Administration of NPBTZ resulted in prolonged drug circulation half-life and increased drug accumulation in tumor tissues.
- NPBTZ significantly enhanced tumor growth suppression in a basal-like TNBC model.
Conclusions:
- PEG-b-PLA nanoparticles serve as an effective delivery system for bortezomib, overcoming its clinical limitations.
- NPBTZ demonstrates significant therapeutic potential for basal-like TNBC by effectively targeting CSCs and enhancing anti-tumor activity.
- This nanoparticle-based drug delivery system offers a promising strategy for improving the treatment outcomes of triple-negative breast cancer.
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