Sorafenib/2800Z Co-Loaded into Cholesterol and PEG Grafted Polylysine NPs for Liver Cancer Treatment
TL;DR: In this article , the authors constructed polylysine polymer nanoparticles modified with cholesterol and GSH-sensitive PEG (mPssPC) to load sorafenib (SOR) and the SIRT7 inhibitor 2800Z to form dual-loaded NPs (S2@PsPCs) to reduce the toxicity and increase efficacy of SOR in liver cancer.
read more
Abstract: The treatment of liver cancer remains challenging due to the low responsiveness of advanced cancer to therapeutic options. Sorafenib is the first line chemotherapeutic drug for advanced liver cancer but is frequently associated with severe side effects lead to discontinuation of chemotherapy. We previously developed a specific SIRT7 inhibitor 2800Z, which suppressed tumor growth and enhanced the chemosensitivity of sorafenib. In this study, we constructed polylysine polymer nanoparticles modified with cholesterol and GSH-sensitive PEG (mPssPC) to load sorafenib (SOR) and the SIRT7 inhibitor 2800Z to form dual-loaded NPs (S2@PsPCs) to reduce the toxicity and increase efficacy of sorafenib in liver cancer. The average size of S2@PsPC NPs was approximately 370 nm and the zeta potential was approximately 50–53 mV. We found that the release of the drugs exhibited pH sensitivity and was significantly accelerated in an acid release medium simulating the tumor environment. In addition, S2@PsPC NPs inhibited the proliferation and induced apoptosis of liver cancer cells in vitro. An in vivo study further revealed that S2@PsPCs showed high specificity to the liver cancer but low affinity and toxicity to the main organs including the heart, kidneys, lungs, and liver. Our data thus further approved the combination of a SIRT7 inhibitor and sorafenib for the treatment of liver cancer and provided new drug delivery system for targeted therapy.
read more
Chat with Paper
AI Agents for this Paper
Find similar papers on Google Scholar, PubMed and Arxiv
Write a critical review of this paper
Analyze citations of this paper to find unaddressed research gaps
Citations
Polypeptide-Based Systems: From Synthesis to Application in Drug Delivery
Mariia Stepanova,Alexey Nikiforov,Tatiana Tennikova,Evgenia Korzhikova-Vlakh +3 more
TL;DR: The advances in the synthesis of polypeptides and their copolymers and the application of these systems for drug delivery in the form of (nano)particles or hydrogels and the development of certain drug nanoformulations for peptides, proteins, gene delivery, cancer therapy, and antimicrobial and anti-inflammatory systems are summarized.
10
SIRT7 promotes Hippo/YAP activation and cancer cell proliferation in hepatocellular carcinoma via suppressing MST1.
Yiying Gu,Cong Ding,Tingzi Yu,Bohao Liu,Wenbin Tang,Zhiqiang Wang,Xiaohui Tang,Gaoshuang Liang,Jinying Peng,Xiangwen Zhang,Zhuan Li +10 more
TL;DR: The previously undescribed function of SIRT7 in regulating the Hippo pathway in HCC is revealed and it is proved that targeting SIRT7 might provide novel therapeutic options for the treatment of liver cancer.
8
The dark side of SIRT7
08 Dec 2023
TL;DR: An in-depth understanding of the role of SIRT7 in cancer carcinogenesis, evolution and progression is provided by elucidating the underlying molecular mechanisms by unveiling the intricate molecular pathways through which SIRT7 exerts its effects on cancer cells.
6
TRIM21 is critical in regulating hepatocellular carcinoma growth and response to therapy by altering the MST1/YAP pathway.
Bo Shu,Ying-Xia Zhou,Guoqiong Lei,Yu Peng,Cong Ding,Zhuan Li,Chao He +6 more
TL;DR: TRIM21 is a key regulator of hepatocellular carcinoma growth and chemoresistance by altering the MST1/YAP pathway.
1
SIRT7 protects against liver fibrosis by suppressing stellate cell activation via TGF-β/SMAD2/3 pathway
Cong Ding,Bohao Liu,Tingzi Yu,Sheng Wang,Jinying Peng,Yiying Gu,Zhuan Li +6 more
TL;DR: SIRT7 suppresses liver fibrosis by inhibiting stellate cell activation through the TGF-β/SMAD2/3 pathway, highlighting its protective role in hepatic fibrosis and suggesting potential therapeutic applications for SIRT7 in liver disease treatment.
1
References
Sorafenib in Advanced Hepatocellular Carcinoma
Josep M. Llovet,Sergio Ricci,Vincenzo Mazzaferro,Philip Hilgard,Edward Gane,Jean-Frédéric Blanc,André Cosme de Oliveira,Armando Santoro,Jean-Luc Raoul,Alejandro Forner,Myron Schwartz,Camillo Porta,Stefan Zeuzem,Luigi Bolondi,Tim F. Greten,Peter R. Galle,Jean Francois Seitz,Ivan Borbath,Dieter Häussinger,Tom Giannaris,Minghua Shan,M. Moscovici,D. Voliotis,Jordi Bruix +23 more
TL;DR: In patients with advanced hepatocellular carcinoma, median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo.
EASL-EORTC clinical practice guidelines : management of hepatocellular carcinoma
Peter R. Galle,Alejandro Forner,Josep M. Llovet,Vincenzo Mazzaferro,Fabio Piscaglia,Jean-Luc Raoul,Peter Schirmacher,Valérie Vilgrain +7 more
TL;DR: The following Clinical Practice Guidelines will give up-to-date advice for the clinical management of patients with hepatocellular carcinoma, as well as providing an in-depth review of all the relevant data leading to the conclusions herein.
10.3K
BAY 43-9006 Exhibits Broad Spectrum Oral Antitumor Activity and Targets the RAF/MEK/ERK Pathway and Receptor Tyrosine Kinases Involved in Tumor Progression and Angiogenesis
Scott Wilhelm,Christopher A. Carter,LiYa Tang,Dean Wilkie,Angela McNabola,Hong Rong,Charles Chen,Xiaomei Zhang,Patrick Vincent,Mark McHugh,Yichen Cao,Jaleel Shujath,Susan Gawlak,Deepa Eveleigh,Bruce Rowley,Li Liu,Lila Adnane,Mark Lynch,Daniel Auclair,Ian W. Taylor,Rich Gedrich,Andrei Voznesensky,Bernd Riedl,Leonard Post,Gideon Bollag,Pamela A. Trail +25 more
TL;DR: Data demonstrate that BAY 43-9006 is a novel dual action RAF kinase and VEGFR inhibitor that targets tumor cell proliferation and tumor angiogenesis.
4.1K
Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
TL;DR: The analysis of two SIR2 mutations supports the idea that this deacetylase activity accounts for silencing, recombination suppression and extension of life span in vivo, and provides a molecular framework of NAD-dependent histone de acetylation that connects metabolism, genomic silencing and ageing in yeast and, perhaps, in higher eukaryotes.
3.6K
The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect.
TL;DR: Molecular mechanisms of factors related to the EPR effect, the unique anatomy of tumor vessels, limitations and techniques to avoid such limitations, augmenting tumor drug delivery, and experimental and clinical findings are discussed.
3.4K