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Sorafenib-Loaded Nanoparticles Based on Biodegradable Dendritic Polymers for Enhanced Therapy of Hepatocellular
Zihuang Li1, Ling Ye2, Jingwen Liu1
1Department of Radiation Oncology, The Second Clinical Medical College of Jinan University, Shenzhen Municipal People's Hospital, Shenzhen 518020, People's Republic of China.
Purpose:
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.
Insights
Novel dendritic polymeric nanoparticles loaded with sorafenib (NP-TPGS-SFB) show enhanced hepatocellular carcinoma (HCC) therapy. This new approach improves drug delivery and reduces side effects for better treatment outcomes.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Sorafenib (SFB) is an effective hepatocellular carcinoma (HCC) treatment but faces limitations like short in vivo half-life and drug resistance.
- Developing advanced drug delivery systems is crucial to overcome these limitations and enhance therapeutic efficacy.
Purpose of the Study:
- To develop a novel sorafenib-loaded dendritic polymeric nanoparticle (NP-TPGS-SFB) for improved hepatocellular carcinoma (HCC) therapy.
- To evaluate the stability, drug release, cellular uptake, cytotoxicity, and in vivo antitumor efficacy of the developed nanoparticles.
Main Methods:
- Fabrication of NP-TPGS-SFB 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).
- Assessment of nanoparticle stability, acid-responsive SFB release, cellular uptake in HepG2 cells, and cytotoxicity via MTT assay.
- Evaluation of in vivo antitumor efficacy in mice bearing HepG2 xenografts.
Main Results:
- NP-TPGS-SFB demonstrated excellent stability and acid-responsive release of sorafenib (SFB).
- Significantly higher cellular uptake efficiency in HepG2 cells was observed for NP-TPGS-SFB compared to NP-PEG-SFB.
- NP-TPGS-SFB exhibited superior cytotoxicity and significantly inhibited tumor growth in vivo with negligible side effects.
Conclusions:
- NP-TPGS-SFB represents a promising novel approach for enhanced hepatocellular carcinoma (HCC) therapy.
- The developed nanoparticle system effectively overcomes the limitations of free sorafenib, offering potential for improved clinical outcomes.
