Single-Shot Local Injection of Microfragmented Fat Tissue Loaded with Paclitaxel Induces Potent Growth Inhibition of Hepatocellular Carcinoma in Nude Mice

Hepatocellular carcinoma (HCC) is poorly beneficiated by intravenous chemotherapy due to inadequate availability of drugs at the tumor site. We previously demonstrated that human micro-fragmented adipose tissue (MFAT) and its devitalized counterpart (DMFAT) could be effective natural scaffolds to de...

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Autores principales:	Giulio Alessandri, Augusto Pessina, Rita Paroni, Luisa Bercich, Francesca Paino, Michele Dei Cas, Moris Cadei, Arnaldo Caruso, Marco Schiariti, Francesco Restelli, Offer Zeira, Carlo Tremolada, Nazario Portolani
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	paclitaxel micro-fragmented fat tissue hepatocarcinoma drug delivery natural scaffold Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/0f6baa87087a4237828c5129b3285387
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spelling	oai:doaj.org-article:0f6baa87087a4237828c5129b32853872021-11-11T15:33:46ZSingle-Shot Local Injection of Microfragmented Fat Tissue Loaded with Paclitaxel Induces Potent Growth Inhibition of Hepatocellular Carcinoma in Nude Mice10.3390/cancers132155052072-6694https://doaj.org/article/0f6baa87087a4237828c5129b32853872021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5505https://doaj.org/toc/2072-6694Hepatocellular carcinoma (HCC) is poorly beneficiated by intravenous chemotherapy due to inadequate availability of drugs at the tumor site. We previously demonstrated that human micro-fragmented adipose tissue (MFAT) and its devitalized counterpart (DMFAT) could be effective natural scaffolds to deliver Paclitaxel (PTX) to tumors in both in vitro and in vivo tests, affecting cancer growth relapse. Here we tested the efficacy of DMFAT-PTX in a well-established HCC in nude mice. MFAT-PTX and DMFAT-PTX preparations were tested for anti-cancer activity in 2D and 3D assays using Hep-3B tumor cells. The efficacy of DMFAT-PTX was evaluated after a single-shot subcutaneous injection near a Hep-3B growing tumor by assessing tumor volumes, apoptosis rate, and drug pharmacokinetics in an in vivo model. Potent antiproliferative activity was seen in both in vitro 2D and 3D tests. Mice treated with DMFAT-PTX (10 mg/kg) produced potent Hep-3B growth inhibition with 33% complete tumor regressions. All treated animals experienced tumor ulceration at the site of DMFAT-PTX injection, which healed spontaneously. Lowering the drug concentration (5 mg/kg) prevented the formation of ulcers, maintaining statistically significant efficacy. Histology revealed a higher number of apoptotic cancer cells intratumorally, suggesting prolonged presence of PTX that was confirmed by the pharmacokinetic analysis. DMFAT may be a potent and valid new tool for local chemotherapy of HCC in an advanced stage of progression, also suggesting potential effectiveness in other human primary inoperable cancers.Giulio AlessandriAugusto PessinaRita ParoniLuisa BercichFrancesca PainoMichele Dei CasMoris CadeiArnaldo CarusoMarco SchiaritiFrancesco RestelliOffer ZeiraCarlo TremoladaNazario PortolaniMDPI AGarticlepaclitaxelmicro-fragmented fat tissuehepatocarcinomadrug deliverynatural scaffoldNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5505, p 5505 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	paclitaxel micro-fragmented fat tissue hepatocarcinoma drug delivery natural scaffold Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	paclitaxel micro-fragmented fat tissue hepatocarcinoma drug delivery natural scaffold Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Giulio Alessandri Augusto Pessina Rita Paroni Luisa Bercich Francesca Paino Michele Dei Cas Moris Cadei Arnaldo Caruso Marco Schiariti Francesco Restelli Offer Zeira Carlo Tremolada Nazario Portolani Single-Shot Local Injection of Microfragmented Fat Tissue Loaded with Paclitaxel Induces Potent Growth Inhibition of Hepatocellular Carcinoma in Nude Mice
description	Hepatocellular carcinoma (HCC) is poorly beneficiated by intravenous chemotherapy due to inadequate availability of drugs at the tumor site. We previously demonstrated that human micro-fragmented adipose tissue (MFAT) and its devitalized counterpart (DMFAT) could be effective natural scaffolds to deliver Paclitaxel (PTX) to tumors in both in vitro and in vivo tests, affecting cancer growth relapse. Here we tested the efficacy of DMFAT-PTX in a well-established HCC in nude mice. MFAT-PTX and DMFAT-PTX preparations were tested for anti-cancer activity in 2D and 3D assays using Hep-3B tumor cells. The efficacy of DMFAT-PTX was evaluated after a single-shot subcutaneous injection near a Hep-3B growing tumor by assessing tumor volumes, apoptosis rate, and drug pharmacokinetics in an in vivo model. Potent antiproliferative activity was seen in both in vitro 2D and 3D tests. Mice treated with DMFAT-PTX (10 mg/kg) produced potent Hep-3B growth inhibition with 33% complete tumor regressions. All treated animals experienced tumor ulceration at the site of DMFAT-PTX injection, which healed spontaneously. Lowering the drug concentration (5 mg/kg) prevented the formation of ulcers, maintaining statistically significant efficacy. Histology revealed a higher number of apoptotic cancer cells intratumorally, suggesting prolonged presence of PTX that was confirmed by the pharmacokinetic analysis. DMFAT may be a potent and valid new tool for local chemotherapy of HCC in an advanced stage of progression, also suggesting potential effectiveness in other human primary inoperable cancers.
format	article
author	Giulio Alessandri Augusto Pessina Rita Paroni Luisa Bercich Francesca Paino Michele Dei Cas Moris Cadei Arnaldo Caruso Marco Schiariti Francesco Restelli Offer Zeira Carlo Tremolada Nazario Portolani
author_facet	Giulio Alessandri Augusto Pessina Rita Paroni Luisa Bercich Francesca Paino Michele Dei Cas Moris Cadei Arnaldo Caruso Marco Schiariti Francesco Restelli Offer Zeira Carlo Tremolada Nazario Portolani
author_sort	Giulio Alessandri
title	Single-Shot Local Injection of Microfragmented Fat Tissue Loaded with Paclitaxel Induces Potent Growth Inhibition of Hepatocellular Carcinoma in Nude Mice
title_short	Single-Shot Local Injection of Microfragmented Fat Tissue Loaded with Paclitaxel Induces Potent Growth Inhibition of Hepatocellular Carcinoma in Nude Mice
title_full	Single-Shot Local Injection of Microfragmented Fat Tissue Loaded with Paclitaxel Induces Potent Growth Inhibition of Hepatocellular Carcinoma in Nude Mice
title_fullStr	Single-Shot Local Injection of Microfragmented Fat Tissue Loaded with Paclitaxel Induces Potent Growth Inhibition of Hepatocellular Carcinoma in Nude Mice
title_full_unstemmed	Single-Shot Local Injection of Microfragmented Fat Tissue Loaded with Paclitaxel Induces Potent Growth Inhibition of Hepatocellular Carcinoma in Nude Mice
title_sort	single-shot local injection of microfragmented fat tissue loaded with paclitaxel induces potent growth inhibition of hepatocellular carcinoma in nude mice
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/0f6baa87087a4237828c5129b3285387
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Single-Shot Local Injection of Microfragmented Fat Tissue Loaded with Paclitaxel Induces Potent Growth Inhibition of Hepatocellular Carcinoma in Nude Mice

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