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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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/21/5505 |
| _version_ | 1797512690284888064 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T06:04:16Z |
| format | Article |
| id | doaj.art-0f6baa87087a4237828c5129b3285387 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T06:04:16Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-0f6baa87087a4237828c5129b32853872023-11-22T20:36:13ZengMDPI AGCancers2072-66942021-11-011321550510.3390/cancers13215505Single-Shot Local Injection of Microfragmented Fat Tissue Loaded with Paclitaxel Induces Potent Growth Inhibition of Hepatocellular Carcinoma in Nude MiceGiulio Alessandri0Augusto Pessina1Rita Paroni2Luisa Bercich3Francesca Paino4Michele Dei Cas5Moris Cadei6Arnaldo Caruso7Marco Schiariti8Francesco Restelli9Offer Zeira10Carlo Tremolada11Nazario Portolani12Cellular Neurobiology Laboratory, Department of Cerebrovascular Diseases, Foundation IRCCS Neurological Institute Carlo Besta, 20133 Milan, ItalyCRC StaMeTec, Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20133 Milan, ItalyClinical biochemistry and Mass Spectrometry Laboratory, Department of Health Sciences, University of Milan, 20122 Milan, ItalyDepartment of Pathology, ASST Spedali Civili of Brescia, 25123 Brescia, ItalyCRC StaMeTec, Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20133 Milan, ItalyClinical biochemistry and Mass Spectrometry Laboratory, Department of Health Sciences, University of Milan, 20122 Milan, ItalySection of Pathological Anatomy DMMT, University of Brescia, 25121 Brescia, ItalyDepartment of Molecular and Translational Medicine, Clinical Microbiology and Virology Section, University of Brescia, 25127 Brescia, ItalyDepartment of Neurosurgery, Foundation IRCCS Neurological Institute Carlo Besta, 20133 Milan, ItalyDepartment of Neurosurgery, Foundation IRCCS Neurological Institute Carlo Besta, 20133 Milan, ItalySan Michele Veterinary Hospital, 26838 Lodi, ItalyImage Regenerative Clinic, Via Mascagni 14, 20122 Milan, ItalyDepartment of Clinical and Experimental Sciences, Surgical Clinic, University of Brescia, 25121 Brescia, ItalyHepatocellular 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.https://www.mdpi.com/2072-6694/13/21/5505paclitaxelmicro-fragmented fat tissuehepatocarcinomadrug deliverynatural scaffold |
| spellingShingle | 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 Cancers paclitaxel micro-fragmented fat tissue hepatocarcinoma drug delivery natural scaffold |
| title | 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_short | 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 |
| topic | paclitaxel micro-fragmented fat tissue hepatocarcinoma drug delivery natural scaffold |
| url | https://www.mdpi.com/2072-6694/13/21/5505 |
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