Journal article Open Access

Vascular-confined multi-passage discoidal nanoconstructs for the low-dose docetaxel inhibition of triple-negative breast cancer growth

Alessia Felici; Alessia Felici; Daniele Di Mascolo; Anna Lisa Palange; Paolo Decuzzi; Luca Bono; Arunkumar Pitchaimani; Simone Lauciello; Miguel Ferreira; Andrea Armirotti

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      <creatorName>Alessia Felici</creatorName>
      <creatorName>Alessia Felici</creatorName>
      <creatorName>Daniele Di Mascolo</creatorName>
      <creatorName>Anna Lisa Palange</creatorName>
      <creatorName>Paolo Decuzzi</creatorName>
      <creatorName>Luca Bono</creatorName>
      <creatorName>Arunkumar Pitchaimani</creatorName>
      <creatorName>Simone Lauciello</creatorName>
      <creatorName>Miguel Ferreira</creatorName>
      <creatorName>Andrea Armirotti</creatorName>
    <title>Vascular-confined multi-passage discoidal nanoconstructs for the low-dose docetaxel inhibition of triple-negative breast cancer growth</title>
  <publisher>INFN Open Access Repository</publisher>
    <subject>European Commission</subject>
    <subject>Electrical and Electronic Engineering</subject>
    <subject>General Materials Science</subject>
    <subject>Condensed Matter Physics</subject>
    <subject>Atomic and Molecular Physics, and Optics</subject>
    <date dateType="Issued">2021-05-19</date>
  <resourceType resourceTypeGeneral="Text">Journal article</resourceType>
    <alternateIdentifier alternateIdentifierType="url"></alternateIdentifier>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.1007/s12274-021-3507-8</relatedIdentifier>
    <relatedIdentifier relatedIdentifierType="URL" relationType="IsPartOf"></relatedIdentifier>
    <rights rightsURI="">Creative Commons Attribution 4.0</rights>
    <rights rightsURI="info:eu-repo/semantics/openAccess">Open Access</rights>
    <description descriptionType="Abstract">AbstractTaxane efficacy in triple negative breast cancer (TNBC) is limited by insufficient tumor accumulation and severe off-target effects. Nanomedicines offer a unique opportunity to enhance the anti-cancer potency of this drug. Here, 1,000 nm × 400 nm discoidal polymeric nanoconstructs (DPN) encapsulating docetaxel (DTXL) and the near infrared compound lipid-Cy5 were engineered. DPN were obtained by filling multiple times cylindrical wells in a poly(vinyl alcohol) template with a polymer mixture comprising poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) diacrylate (PEG-DA) chains together with therapeutic and imaging agents. The resulting "multi-passage" DPN exhibited higher DTXL loading, lipid-Cy5 stability, and stiffness as compared to the conventional "single-passage" approach. Confocal microscopy confirmed that DTXL-DPN were not taken up by MDA-MB-231 cells but would rather sit next to the cell membrane and slowly release DTXL thereof. Empty DPN had no toxicity on TNBC cells, whereas DTXL-DPN presented a cytotoxic potential comparable to free DTXL (IC50 = 2.6 nM ± 1.0 nM vs. 7.0 nM ± 1.09 nM at 72 h). In orthotopic murine models, DPN accumulated in TNBC more efficiently than free-DTXL. With only 2 mg/kg DTXL, intravenously administered every 2 days for a total of 13 treatments, DTXL-DPN induced tumor regression and were associated to an overall 80% survival rate as opposed to a 30% survival rate for free-DTXL, at 120 days. All untreated mice succumbed before 90 days. Collectively, this data demonstrates that vascular confined multi-passage DPN, biomimicking the behavior of circulating platelets, can efficiently deliver chemotherapeutic molecules to malignant tissues and effectively treat orthotopic TNBC at minimal taxane doses.</description>
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