Microfragmented human fat tissue is a natural scaffold for drug delivery: Potential application in cancer chemotherapy

J Control Release. 2019 May 28;302:2-18. doi: 10.1016/j.jconrel.2019.03.016. Epub 2019 Mar 16.

Abstract

Localization of chemotherapy at the tumor site can improve therapeutic efficacy and reduce systemic toxicity. In previous studies we have shown that mesenchymal stromal cells (MSCs) isolated from bone marrow or adipose tissue can be loaded with the anti-cancer drug Paclitaxel (PTX) and kill cancer cells when localized nearby. We here investigated the capacity of human micro-fragmented adipose tissue (MFAT), used as a natural scaffold of MSCs, to deliver PTX with the idea to improve local drug concentration and to prolong the therapeutic activity. Surprisingly, we found that both fresh but also devitalized MFAT (DMFAT) (by freezing/thawing procedure) were able to deliver and release significant amount of PTX, killing several human cancer cell lines in vitro with a long lasting activity. In an orthotopic mice model of Neuroblastoma (NB) transplant, DMFAT loaded with PTX prevents or delays NB relapse when placed in the surgical area of tumor resection, without any collateral toxicity. We concluded that MFAT, but also DMFAT, may represent very innovative natural biomaterials able to localize and release anti-cancer molecules at the tumor site, helping to fight cancer in human.

Keywords: Anti-cancer chemotherapy; Biomaterials; Drug delivery; Micro-fragmented adipose tissue; Natural scaffold.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / chemistry*
  • Adipose Tissue / metabolism
  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / metabolism
  • Biological Products / chemistry*
  • Biological Products / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Carriers / chemistry*
  • Drug Liberation
  • Female
  • Fluorescent Dyes / chemistry
  • Humans
  • Mice, Inbred BALB C
  • Neoplasms, Experimental
  • Neuroblastoma / drug therapy*
  • Optical Imaging
  • Paclitaxel / chemistry*
  • Paclitaxel / pharmacokinetics
  • Paclitaxel / therapeutic use
  • Protein Conformation

Substances

  • Antineoplastic Agents
  • Biocompatible Materials
  • Biological Products
  • Drug Carriers
  • Fluorescent Dyes
  • Paclitaxel