N-Acetylgalactosamine-Decorated Nanoliposomes for Targeted Delivery of Paclitaxel to Hepatocellular Carcinoma

Retinoic acid (R) grafted chitosan (C) copolymers with different degree of substitution of retinoic acid on the chitosan were synthesized. Retinoic acid targeted chitosan-albumin nanoparticles were prepared for targeted delivery of doxorubicin in hepatocellular carcinoma by coacervation method. Physical properties of nanoparticles including particle size, zeta potential, drug loading efficiency, and drug release profiles were studied. TEM micrographs were taken to see the morphology of nanoparticles. The cytotoxicity of doxorubicin-loaded nanoparticles was studied on HepG2 cells using MTT assay and their cellular uptake by fluorescence microscopy. FTIR and1HNMR spectra confirmed successful production of RC conjugate which was used in production of the targeted RC-albumin nanoparticles. IC50of drug loaded in these nanoparticles reduced to half and one-third compared to nontargeted nanoparticles and free drug, respectively.

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Selective targeted delivery of doxorubicin via conjugating to anti-CD24 antibody results in enhanced antitumor potency for hepatocellular carcinoma both in vitro and in vivo

Journal of Cancer Research and Clinical Oncology ◽

10.1007/s00432-017-2436-0 ◽

2017 ◽

Vol 143 (10) ◽

pp. 1929-1940 ◽

Cited By ~ 3

Author(s):

Zhaoxiong Ma ◽

Hua He ◽

Fumou Sun ◽

Yao Xu ◽

Xuequn Huang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Targeted Delivery

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Engineered Exosomes for the Targeted Delivery of a Novel Therapeutic Cargo to Enhance Sorafenib-Mediated Ferroptosis in Hepatocellular Carcinoma.

10.21203/rs.3.rs-1108956/v1 ◽

2021 ◽

Author(s):

Xiaoju Li ◽

Qianqian Yu ◽

Xinyan Guo ◽

Chenlin Liu ◽

Runze Zhao ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Targeted Delivery ◽

Rna Recognition Motif ◽

Advanced Hepatocellular Carcinoma ◽

Rna Recognition ◽

Sorafenib Treatment ◽

Recognition Motif ◽

Interfering Rna

Abstract Background Sorafenib is one of the few effective first-line drugs approved for the treatment of advanced hepatocellular carcinoma (HCC). However, the development of drug resistance is common among individuals with HCC. Thus, there is an urgent need to solve this problem. Results Recent evidence indicated that the anticancer activity of sorafenib mainly relies on the induction of ferroptosis. In our study, genes that suppress ferroptosis, especially GPX4 and DHODH, were enriched in sorafenib-resistant cells and primary tissues and were associated with poor prognosis of HCC patients who received sorafenib treatment. Therefore, silencing GPX4 and DHODH might be a novel and effective strategy to overcome sorafenib resistance. Here, a novel ferroptosis inducer comprising a multiplex small interfering RNA (multi-siRNA) capable of simultaneously silencing GPX4 and DHODH was created. Then, exosomes with high multi-siRNA loading and HCC-specific targeting were established by fusing the SP94 peptide and the N-terminal RNA recognition motif (RRM) of U1-A with the exosomal membrane protein Lamp2b. The results from the in vitro and in vivo experiments indicate that this tumor-targeting nanodelivery system (ExoSP94−lamp2b−RRM-multi-siRNA) could enhance sorafenib-induced ferroptosis and overcome sorafenib resistance, which might open a new avenue for clinically overcoming sorafenib resistance. Conclusions We designed HCC-targeted exosomes (ExoSP94−Lamp2b−RRM) that can deliver a novel ferroptosis inducer. Our data show that ExoSP94−lamp2b−RRM-multi-siRNA could enhance sorafenib-induced ferroptosis by silencing GPX4 and DHODH expression and consequently increase HCC sensitivity to sorafenib. This is the first study to describe the use of engineered exosomes to overcome acquired sorafenib resistance with respect to ferroptosis.

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Doxorubicin and ABT-199 Coencapsulated Nanocarriers for Targeted Delivery and Synergistic Treatment against Hepatocellular Carcinoma

Journal of Nanomaterials ◽

10.1155/2019/5274598 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13

Author(s):

Yun Zhou ◽

Ke Li ◽

Fan Li ◽

Shuang Han ◽

Yang Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Combination Chemotherapy ◽

Targeted Delivery ◽

Fluorescent Imaging ◽

Targeted Nanoparticles ◽

Continuous Release ◽

Tumor Tissues ◽

Dual Drug

For the patients with hepatocellular carcinoma (HCC), conventional chemotherapy is insufficient or has no benefit. Although combination chemotherapy has been proven as an efficient strategy to enhance anti-HCC efficacy, some barriers, such as low bioavailability and side effects, are limiting clinical development. In order to overcome disadvantages of combination chemotherapy in HCC, targeted nanoparticles (NPs) simultaneously loaded with doxorubicin (DOX) and ABT-199 in an optimal synergistic ratio were developed. First, the most synergistic combination with DOX was screened from ABT-199, ABT-263, and ABT-737. Among them, ABT-199 showed optimal synergy with DOX in a ratio of 10 : 1. Then, cationic amphipathic starch (CSaSt) and hyaluronic acid (HA) were used in coencapsulations of those two drugs. Dual-drug synergistic nanoparticles (DDS NPs) were constructed by absorption of DOX NPs around ABT-199 micelles with an optimal ratio via electrostatic interaction. The shape of DDS NPs was similar to a raspberry, and the size was 112.6±13.4 nm. The encapsulation efficiencies of DOX and ABT-199 in DDS NPs were 90.2±4.3% and 94.7±2.8%, respectively; meanwhile, the drug loadings were 1.5±0.4% and 14.1±1.1%, respectively. After 72 h of dialysis, 95% of ABT-199 remained and less than 50% of DOX was released. In vitro investigation showed that the drugs in DDS NPs maintained the treated effect in three HCC cell lines; moreover, DDS NPs could perform intracellular delivery of dual drugs and exhibited continuous release of the drugs into different targets. Low in vivo toxicity was found after the acute toxicity test. In vivo fluorescent imaging revealed that DDS NPs could efficiently target and accumulate in the tumor tissues and be maintained more than 72 h after intravenous injection. Compared with free drugs, DDS NPs with the same dosages exhibited a more significant antitumor effect in the HCC xenograft mouse model. The results indicated that DDS NPs have great potential in HCC chemotherapy.

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A novel targeted delivery system for drug-resistant hepatocellular carcinoma therapy

Nanoscale ◽

10.1039/d0nr01908a ◽

2020 ◽

Vol 12 (32) ◽

pp. 17029-17044

Author(s):

Li Xiao ◽

Yang Hou ◽

Huimin He ◽

Sinan Cheng ◽

Yifan Hou ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Targeted Therapy ◽

Delivery System ◽

Targeted Delivery ◽

Drug Resistant ◽

Efficient Approach ◽

Targeted Delivery System

HCSP4-Lipo-DOX-miR101 is a novel and efficient approach for HCC targeted therapy with MDR inhibition in vitro and in vivo.

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Hepatocellular Carcinoma Targeting and Pharmacodynamics of Paclitaxel Nanoliposomes Modified by Glycyrrhetinic Acid and Ferric Tetroxide

Current Topics in Medicinal Chemistry ◽

10.2174/1568026621666210621090005 ◽

2021 ◽

Vol 21 ◽

Author(s):

Ling Zhao ◽

Leyi Liang ◽

Mimi Guo ◽

Ming Li ◽

Xuesong Yu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Targeted Delivery ◽

Average Particle Size ◽

In Vitro Release ◽

Glycyrrhetinic Acid ◽

Migration And Invasion ◽

Average Particle ◽

Hcc Cells

Aims: Research on developing targeted delivery of anticancer drugs for the treatment of hepatocellular carcinoma (HCC) is ongoing. This study aimed at synthesizing nanoliposomes modified by glycyrrhetinic acid (GA) and ferric tetroxide (Fe3O4) for targeted delivery of paclitaxel for selective and specific therapy of HCC. Objective: During this project, GA and Fe3O4 were used to jointly modify the active targeting and magnetic orientation of paclitaxel nanoliposomes for enhanced targeting of HCC to improve the efficacy, while reducing the systemic toxicity and side effects of the drug. Methods: In this study, liposomes were prepared to utilize a thin film dispersion method, in which the average particle size of GA/Fe3O4-PTX-LP was 148.9 ± 2.3 nm, and the average Zeta potential was -23.2 ± 3 mV. Based on the TEM characterization, GA/Fe3O4-PTX-LP is a closed particle with bilayer membranes. In vitro release assessments of the drug indicated that the release of GA/Fe3O4-PTX-LP was sustained. Results: In vitro cell tests have demonstrated that GA/Fe3O 4-PTX-LP can inhibit the proliferation, affect the morphology, migration and invasion, and interfere with the cycle of HCC cells. Uptake tests have confirmed that GA/Fe3O4-PTX-LP can promote the uptake of the drug in HCC cells. Conclusion: In vivo targeting experiments have shown that GA/Fe3O4-PTX-LP has a strong ability to target tumors. In vivo antitumor assessments have proven that GA/Fe3O4-PTX-LP can inhibit tumor growth without obvious toxicity. This project provides a promising nano-targeted drug delivery system for the treatment of HCC.

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Surface Engineering of Nanoparticles for Targeted Delivery to Hepatocellular Carcinoma

Small ◽

10.1002/smll.201702037 ◽

2017 ◽

Vol 14 (5) ◽

pp. 1702037 ◽

Cited By ~ 25

Author(s):

Jingxiong Lu ◽

Jin Wang ◽

Daishun Ling

Keyword(s):

Hepatocellular Carcinoma ◽

Targeted Delivery ◽

Surface Engineering

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