Development and characterization of sorafenib-loaded PLGA nanoparticles for the systemic treatment of liver fibrosis

Lin, Ts-Ting; Gao, Deyun; Liu, Ya-Chi; Sung, Yun‐Chieh; Wan, Dehui; Liu, Jiayu; Chiang, Tsaiyu; Wang, Liying; Chen, Yunching

doi:10.1016/j.jconrel.2015.11.003

Cited by 93 publications

(49 citation statements)

References 31 publications

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“…4a, to co-deliver sorafenib with a MEK inhibitor into HCC. To this end, we loaded sorafenib and the MEK inhibitor AZD6244 into NPs developed as previously described with several modifications2728. The average diameters of drug-loaded TTNPs determined by DLS were 139.7 ± 9.7 nm, with poly-dispersity indexes (PDIs) of 0.425 ± 0.057.…”

Section: Resultsmentioning

confidence: 99%

Overcoming sorafenib evasion in hepatocellular carcinoma using CXCR4-targeted nanoparticles to co-deliver MEK-inhibitors

Chen

Liu

Sung

et al. 2017

Sci Rep

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Sorafenib is a RAF inhibitor approved for several cancers, including hepatocellular carcinoma (HCC). Inhibition of RAF kinases can induce a dose-dependent “paradoxical” upregulation of the downstream mitogen-activated protein kinase (MAPK) pathway in cancer cells. It is unknown whether “paradoxical” ERK activation occurs after sorafenib therapy in HCC, and if so, if it impacts the therapeutic efficacy. Here, we demonstrate that RAF inhibition by sorafenib rapidly leads to RAF dimerization and ERK activation in HCCs, which contributes to treatment evasion. The transactivation of RAF dimers and ERK signaling promotes HCC cell survival, prevents apoptosis via downregulation of BIM and achieves immunosuppression by MAPK/NF-kB-dependent activation of PD-L1 gene expression. To overcome treatment evasion and reduce systemic effects, we developed CXCR4-targeted nanoparticles to co-deliver sorafenib with the MEK inhibitor AZD6244 in HCC. Using this approach, we preferentially and efficiently inactivated RAF/ERK, upregulated BIM and down-regulated PD-L1 expression in HCC, and facilitated intra-tumoral infiltration of cytotoxic CD8+ T cells. These effects resulted in a profound delay in tumor growth. Thus, this nano-delivery strategy to selectively target tumors and prevent the paradoxical ERK activation could increase the feasibility of dual RAF/MEK inhibition to overcome sorafenib treatment escape in HCC.

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Section: Resultsmentioning

confidence: 99%

Overcoming sorafenib evasion in hepatocellular carcinoma using CXCR4-targeted nanoparticles to co-deliver MEK-inhibitors

Chen

Liu

Sung

et al. 2017

Sci Rep

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“…The drug loading content (LC) and drug encapsulation efficiency (EE) of the SFB-loaded NPs were both quantified in line with the previous work. 40…”

Section: Drug Loading Content and Encapsulation Efficiencymentioning

confidence: 99%

<p>Sorafenib-Loaded Nanoparticles Based on Biodegradable Dendritic Polymers for Enhanced Therapy of Hepatocellular Carcinoma</p>

et al. 2020

IJN

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In spite of its enhanced efficacy and reduced side effects in clinical hepatocellular carcinoma (HCC) therapy, the therapeutic efficacy of antitumor angiogenesis inhibitor sorafenib (SFB) is still restricted due to short in vivo half-life and drug resistance. Here, a novel SFB-loaded dendritic polymeric nanoparticle (NP-TPGS-SFB) was developed for enhanced therapy of HCC. Methods: NP-TPGS-SFB was fabricated by encapsulating SFB with biodegradable dendritic polymers poly(amidoamine)-poly(γ-benzyl-L-Glutamate)-b-D-α-tocopheryl polyethylene glycol 1000 succinate (PAM-PBLG-b-TPGS). Results: NP-TPGS-SFB exhibited excellent stability and achieved acid-responsive release of SFB. It also exhibited much higher cellular uptake efficiency in HepG2 human liver cells than PEG-conjugated NP (NP-PEG-SFB). Furthermore, MTT assay confirmed that NP-TPGS-SFB induced higher cytotoxicity than NP-PEG-SFB and free SFB, respectively. Lastly, NP-TPGS-SFB significantly inhibited tumor growth in mice bearing HepG2 xenografts, with negligible side effects. Conclusion: Our result suggests that NP-TPGS-SFB may be a novel approach for enhanced therapy of HCC with promising potential.

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“…Recently, substantial research efforts were directed towards developing and extending the applications of biomolecules by integrating the biomolecules with biological nanoparticles such as polysaccharides and lipids (Liao W. et al, 2016;Rassu G. et al, 2015) and other types of nanoparticles including metals (Chinen A.B. et al, 2015;Politi J. et al, 2015), metal oxides (Cao Y. et al, 2016;Shahrestani H. et al, 2016) and polymers (Cavalli R. et al, 2011;Lin T.-T. et al, 2016) through various conjugation strategies ( Table 2). …”

Section: Integrated Biomolecule-nanoparticle Systemsmentioning

confidence: 99%

Nanoparticles Carrying Biological Molecules: Recent Advances and Applications

Saallah

Lenggoro

2018

KONA

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In the past few decades, enormous advances have been achieved in the field of particle technology and the trend has been shifted from macro to micro and recently to the nanoscale. Integration of nanotechnology and biotechnology has paved the way to the development of biological nanoparticles, derived from biomolecules, and biomolecule-nanoparticle conjugates for numerous applications. This review provides an overview of various types of biological nanoparticles and the methods of their fabrication with primary emphasis on the drying methods, particularly on the newly emerging technique, the electrospraying. Recent advances in the integration of biomolecules with nanoparticles in the past five years to present are also discussed. Finally, the application of the biomolecule-nanoparticle conjugates in various fields including medicals and pharmaceuticals, biosensors and bioelectronics, foods, and agricultures are also highlighted.

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Development and characterization of sorafenib-loaded PLGA nanoparticles for the systemic treatment of liver fibrosis

Cited by 93 publications

References 31 publications

Overcoming sorafenib evasion in hepatocellular carcinoma using CXCR4-targeted nanoparticles to co-deliver MEK-inhibitors

Overcoming sorafenib evasion in hepatocellular carcinoma using CXCR4-targeted nanoparticles to co-deliver MEK-inhibitors

<p>Sorafenib-Loaded Nanoparticles Based on Biodegradable Dendritic Polymers for Enhanced Therapy of Hepatocellular Carcinoma</p>

Nanoparticles Carrying Biological Molecules: Recent Advances and Applications

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