May 19, 2021 Journal article Open Access

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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{
  "DOI": "10.1007/s12274-021-3507-8", 
  "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 \u00d7 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 \u00b1 1.0 nM vs. 7.0 nM \u00b1 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.", 
  "author": [
    {
      "family": "Alessia Felici"
    }, 
    {
      "family": "Alessia Felici"
    }, 
    {
      "family": "Daniele Di Mascolo"
    }, 
    {
      "family": "Anna Lisa Palange"
    }, 
    {
      "family": "Paolo Decuzzi"
    }, 
    {
      "family": "Luca Bono"
    }, 
    {
      "family": "Arunkumar Pitchaimani"
    }, 
    {
      "family": "Simone Lauciello"
    }, 
    {
      "family": "Miguel Ferreira"
    }, 
    {
      "family": "Andrea Armirotti"
    }
  ], 
  "id": "81427", 
  "issued": {
    "date-parts": [
      [
        2021, 
        5, 
        19
      ]
    ]
  }, 
  "language": "eng", 
  "note": "", 
  "title": "Vascular-confined multi-passage discoidal nanoconstructs for the low-dose docetaxel inhibition of triple-negative breast cancer growth", 
  "type": "article-journal"
}