Multifunctional "core-shell" nanoparticles-based gene delivery for treatment of aggressive melanoma
Abstract
Gene therapy may be a promising and powerful strategy for cancer treatment, but efficient targeted gene delivery in vivo has so far remained challenging. Here, we developed a well-tailored and versatile "core-shell" ternary system (RRPHC) of systemic gene delivery for treatment of aggressive melanoma. The capsid-like "shell" of this system was engineered to mediate depth penetration to tissues, simultaneously target the CD44 receptors and integrin α v β 3 receptors overexpressed on neovasculature and most malignant tumor cells, while the "core" was responsible for nucleus-targeting and effective transfection. The RRPHC ternary complexes enhanced cellular uptake via dual receptor-mediated endocytosis, improved the endosomal escape and significantly promoted the plasmid penetration into the nucleus. Notably, RRPHC ternary complexes exhibited ultra-high gene transfection efficiency (∼100% in B16F10 cells), which surpassed that of commercial transfection agents, PEI 25K, Lipofectamine 2000 and even Lipofectamine 3000. Especially, RRPHC ternary complexes showed excellent serum resistance and remained high gene transfection efficacy (∼100%) even in medium containing 30% serum. In vivo biodistribution imaging demonstrated RRPHC ternary complexes possessed much more accumulation and extensive distribution throughout tumor regions while minimal location in other organs. Furthermore, systemic delivery of the pro-apoptotic mTRAIL gene to tumor xenografts by RRPHC ternary complexes resulted in remarkable inhibition of melanoma, with no systemic toxicity. These results demonstrated that the designed novel RRPHC ternary complexes might be a promising gene delivery system for targeted cancer therapy in vivo.
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Due to overexpression of αvβ3 integrin receptors on tumor vasculature, nanoparticles decorated with RGD peptide have more access to targeted tumor tissues.
“For example, due to the overexpression of αvβ3 integrin receptors on tumor vasculature, the nanoparticles decorated with arginine-glycine-glutamic acid (RGD) peptide, a ligand for αvβ3 integrin receptors, have more access to the targeted tumor tissues [163–165].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [164]
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- Authors
- Li, L., Song, L., Yang, X., Li, X., Wu, Y., He, T., Wang, N., Yang, S., Zeng, Y., Yang, L., Wu, Q., Wei, Y., & Gong, C.
- Affiliations
- Sichuan University (CN)
- Xiamen University (CN)
- Corresponding author
- Gong, Changyang
- ORCID
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2016-12
- Volume
- 111
- Pages
- 124-137
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W2527474055
- Cited by
- 62
- References
- 52
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 5 · 2023: 6 · 2022: 6 · 2021: 8 · 2020: 5 · 2019: 10 · 2018: 11 · 2017: 5
- FWCI
- 4.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Young Top-notch Talent Program and Distinguished Young Scholars of Sichuan University (2015SCU04A42)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
- Keywords
- core-shell nanoparticles, gene delivery, melanoma, CD44 receptor, integrin αvβ3, endosomal escape, serum resistance, tissue distribution, systemic gene therapy, B16F10 melanoma cells, tumor xenografts
- MeSH terms
- Animals, Female, Melanoma, Mice, Inbred C57BL, Neoplasm Invasiveness, Particle Size, Plasmids, Genetic Therapy, Treatment Outcome, Gene Transfer Techniques, Cell Line, Tumor, Mice, Nanocapsules, Nanopores
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