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Published on: June 23, 2020
Tuning Peptide-Based Nanofibers for Achieving Selective Doxorubicin Delivery in Triple-Negative Breast Cancer
Rosa Bellavita1, Marialuisa Piccolo1, Linda Leone2
1Department of Pharmacy, School of Medicine, University of Naples 'Federico II', Napoli, Italy.
Introduction:
The design of delivery tools that efficiently transport drugs into cells remains a major challenge in drug development for most pathological conditions. Triple-negative breast cancer (TNBC) is a very aggressive subtype of breast cancer with poor prognosis and limited effective therapeutic options.
Purpose:
In TNBC treatment, chemotherapy remains the milestone, and doxorubicin (Dox) represents the first-line systemic treatment; however, its non-selective distribution causes a cascade of side effects. To address these problems, we developed a delivery platform based on the self-assembly of amphiphilic peptides carrying several moieties on their surfaces, aimed at targeting, enhancing penetration, and therapy.
Methods:
Through a single-step self-assembly process, we used amphiphilic peptides to obtain nanofibers decorated on their surfaces with the selected moieties. The surface of the nanofiber was decorated with a cell-penetrating peptide (gH625), an EGFR-targeting peptide (P22), and Dox bound to the cleavage sequence selectively recognized and cleaved by MMP-9 to obtain on-demand drug release. Detailed physicochemical and cellular analyses were performed.
Results:
The obtained nanofiber (NF-Dox) had a length of 250 nm and a diameter of 10 nm, and it was stable under dilution, ionic strength, and different pH environments. The biological results showed that the presence of gH625 favored the complete internalization of NF-Dox after 1h in MDA-MB 231 cells, mainly through a translocation mechanism. Interestingly, we observed the absence of toxicity of the carrier (NF) on both healthy cells such as HaCaT and TNBC cancer lines, while a similar antiproliferative effect was observed on TNBC cells after the treatment with the free-Dox at 50 µM and NF-Dox carrying 7.5 µM of Dox.
Discussion:
We envision that this platform is extremely versatile and can be used to efficiently carry and deliver diverse moieties. The knowledge acquired from this study will provide important guidelines for applications in basic research and biomedicine.
Insights
Researchers developed a novel peptide nanofiber platform for targeted drug delivery in triple-negative breast cancer (TNBC). This system efficiently delivers doxorubicin (Dox) to cancer cells, minimizing side effects and showing promise for improved TNBC therapy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options.
- Current chemotherapy, like doxorubicin (Dox), has non-selective distribution and significant side effects.
- Efficient intracellular drug delivery remains a critical challenge in cancer therapy.
Purpose of the Study:
- To develop a versatile peptide-based nanofiber platform for targeted drug delivery in TNBC.
- To enhance drug penetration and achieve on-demand drug release.
- To improve the therapeutic efficacy of doxorubicin while reducing systemic toxicity.
Main Methods:
- Self-assembly of amphiphilic peptides into nanofibers.
- Surface functionalization with a cell-penetrating peptide (gH625) and an EGFR-targeting peptide (P22).
- Loading of doxorubicin (Dox) onto nanofibers via an MMP-9 cleavable sequence for targeted release.
Main Results:
- Obtained stable nanofibers (NF-Dox) with dimensions of 250 nm length and 10 nm diameter.
- Demonstrated efficient internalization of NF-Dox into MDA-MB 231 cells within 1 hour, primarily via translocation.
- Showed no toxicity of the carrier (NF) on healthy or cancer cells, with comparable antiproliferative effects of NF-Dox to free Dox at reduced concentrations.
Conclusions:
- The developed peptide nanofiber platform is a versatile and effective system for targeted drug delivery.
- This platform enables efficient intracellular drug delivery and on-demand release, showing potential for improved TNBC treatment.
- The findings provide a foundation for applying this platform in broader biomedical research and therapeutic strategies.
