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Chitosan Nanoparticles for Therapy and Theranostics of Hepatocellular Carcinoma (HCC) and Liver-Targeting.

ABSTRACT: Chitosan nanoparticles are well-known delivery systems widely used as polymeric carriers in the field of nanomedicine. Chitosan is a carbohydrate of natural origin: it is a biodegradable, biocompatible, mucoadhesive, polycationic polymer and it is endowed with penetration enhancer properties. Furthermore, it can be easily derivatized. Hepatocellular carcinoma (HCC) represents a remarkable health problem because current therapies, that include surgery, liver transplantation, trans-arterial embolization, chemoembolization and chemotherapy, present significant limitations due to the high risk of recurrence, to a lack of drug selectivity and to other serious side effects. Therefore, there is the need for new therapeutic strategies and for improving the liver-targeting to HCC. Nanomedicine consists in the use of nanoscale carriers as delivery systems to target and deliver drugs and/or diagnostic agents to specific organs or tissues. Chitosan and its derivatives can be successfully used in the preparation of nanoparticles that, for their peculiar surface-properties, can specifically interact with liver tumor, by passive and active targeting. This review concerns the use of chitosan nanoparticles for the therapy and theranostics of HCC and liver-targeting.

SUBMITTER: Bonferoni MC

PROVIDER: S-EPMC7279387 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Chitosan Nanoparticles for Therapy and Theranostics of Hepatocellular Carcinoma (HCC) and Liver-Targeting.

Bonferoni Maria Cristina MC Gavini Elisabetta E Rassu Giovanna G Maestri Marcello M Giunchedi Paolo P

Nanomaterials (Basel, Switzerland) 20200430 5

Chitosan nanoparticles are well-known delivery systems widely used as polymeric carriers in the field of nanomedicine. Chitosan is a carbohydrate of natural origin: it is a biodegradable, biocompatible, mucoadhesive, polycationic polymer and it is endowed with penetration enhancer properties. Furthermore, it can be easily derivatized. Hepatocellular carcinoma (HCC) represents a remarkable health problem because current therapies, that include surgery, liver transplantation, trans-arterial emboli ...[more]

PMID: 32365938

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Project description:Hepatocellular carcinoma (HCC) is one of the world's most risky diseases due to the lack of clear and cost-effective therapeutic targets. Currently, the toxicity of conventional chemotherapeutic medications and the development of multidrug resistance is driving research into targeted therapies. The nano-biomedical field's potential for developing an effective therapeutic nano-sized drug delivery system is viewed as a significant pharmaceutical trend for the encapsulation and release of numerous anticancer therapies. In this regard, current research is centered on the creation of biodegradable chitosan nanoparticles (CSNPs) for the selective and sustained release of bee venom into liver cancer cells. Furthermore, surface modification with polyethylene glycol (PEG) and GE11 peptide-conjugated bee venom-CSNPs allows for the targeting of EGFR-overexpressed liver cancer cells. A series of in vitro and in vivo cellular analyses were used to investigate the antitumor effects and mechanisms of targeted bee venom-CSNPs. Targeted bee venom-CSNPs, in particular, were found to have higher cytotoxicity against HepG2 cells than SMMC-7721 cells, as well as stronger cellular uptake and a substantial reduction in cell migration, leading to improved cancer suppression. It also promotes cancer cell death in EGFR overexpressed HepG2 cells by boosting reactive oxygen species, activating mitochondria-dependent pathways, inhibiting EGFR-stimulated MEK/ERK pathway, and elevating p38-MAPK in comparison to native bee venom. In hepatocellular carcinoma (HCC)-induced mice, it has anti-cancer properties against tumor tissue. It also improved liver function and architecture without causing any noticeable toxic side effects, as well as inhibiting tumor growth by activating the apoptotic pathway. The design of this cancer-targeted nanoparticle establishes GE11-bee venom-CSNPs as a potential chemotherapeutic treatment for EGFR over-expressed malignancies. Finally, our work elucidates the molecular mechanism underlying the anticancer selectivity of targeted bee venom-CSNPs and outlines therapeutic strategies to target liver cancer.

Project description:BACKGROUND: The laparoscopic approach for liver resections is still limited and controversial. Nevertheless the advantages connected with a mini-invasive approach are significant, especially in cirrhotic patients. In recent years the progress of laparoscopic procedures and the development of new and dedicated technologies have made endoscopic hepatic surgery feasible and safe. The aim of this study was to report the results of our experience in laparoscopic liver surgery for hepatocellular carcinoma (HCC) in cirrhotic patients. METHODS: From 2000 to 2003, 16 patients (10 male, 6 female; age 48-69 years; mean age 60.1 years) with HCC and associated severe but well compensated liver cirrhosis underwent laparoscopic hepatic resections at our department. Mean tumour size was 2.9 cm (range 1-3.9). Seven of these lesions were in the left liver and nine in the right lobe. Laparoscopy was performed under CO(2) pneumoperitoneum. The liver was always examined using laparoscopic ultrasound (US) to confirm the extension of the lesions and their relationships to the vasculature. The Pringle manoeuvre was not used. The transection of liver parenchyma was obtained by the use of a harmonic scalpel. The specimens were placed in a plastic bag and removed without contact to the abdominal wall. RESULTS: There was one conversion to laparotomy for inadequate exposure. In the remaining 15 patients we performed 13 non-anatomical resections, I segmentectomy and I anatomical left lobectomy. The mean operative time was 152 min (range 80-180). Mean blood loss was 280 ml and none of the patients required blood transfusions. In two patients the resection margin was <1 cm but the capsule was not infiltrated at histology. One patient died on the third postoperative day from a severe respiratory distress syndrome. Major morbidities occurred in two patients who developed moderate postoperative ascites, which resolved successfully with conservative treatment. The mean postoperative hospital stay was 8.8 days. Mean follow-up time has been 18 months, and to date no recurrences at the site of resection or port-site metastases have been observed. DISCUSSION: Limited laparoscopic liver resections in cirrhotic patients are technically feasible with a low complication rate when careful selection criteria are followed (hepatic involvement limited and located in the left or anterior right segments, tumour size smaller than 5 cm, Child-Pugh class A). This approach could be considered the best option for the treatment of small esophitic or subcapsular HCC on well compensated cirrhosis and a useful option when it is necessary to perform a left lateral anatomical resection or non-anatomical resection in well selected patients. In fact the mini-invasive approach can minimise the postoperative morbidity rate, which is still too high in this group of patients. It must be performed in highly specialised units by surgeons assisted by all requested technologies and with extensive experience in hepatobiliary and advanced laparoscopic surgery.

Dataset Information

Chitosan Nanoparticles for Therapy and Theranostics of Hepatocellular Carcinoma (HCC) and Liver-Targeting.

Publications

Chitosan Nanoparticles for Therapy and Theranostics of Hepatocellular Carcinoma (HCC) and Liver-Targeting.

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