pH-Responsive Lipid Nanocapsules: A Promising Strategy for Improved Resistant Melanoma Cell Internalization
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Updated: Aug 7, 2026
Solid Lipid Nanoparticles SLNs for Intracellular Targeting Applications
Published on: November 17, 2015
Vincent Pautu1,2, Elise Lepeltier1, Adélie Mellinger1
1Micro & Nanomedecines Translationnelles (MINT), University of Angers, Inserm, The National Center for Scientific Research (CNRS), SFR ICAT, F-49000 Angers, France.
Abstract:
Despite significant advances in melanoma therapy, low response rates and multidrug resistance (MDR) have been described, reducing the anticancer efficacy of the administered molecules. Among the causes to explain these resistances, the decreased intratumoral pH is known to potentiate MDR and to reduce the sensitivity to anticancer molecules. Nanomedicines have been widely exploited as the carriers of MDR reversing molecules. Lipid nanocapsules (LNC) are nanoparticles that have already demonstrated their ability to improve cancer treatment. Here, LNC were modified with novel copolymers that combine N-vinylpyrrolidone (NVP) to impart stealth properties and vinyl imidazole (Vim), providing pH-responsive ability to address classical chemoresistance by improving tumor cell entry. These copolymers could be post-inserted at the LNC surface, leading to the property of going from neutral charge under physiological pH to positive charge under acidic conditions. LNC modified with polymer P5 (C18H37-P(NVP21-co-Vim15)) showed in vitro pH-responsive properties characterized by an enhanced cellular uptake under acidic conditions. Moreover, P5 surface modification led to an increased biological effect by protecting the nanocarrier from opsonization by complement activation. These data suggest that pH-sensitive LNC responds to what is expected from a promising nanocarrier to target metastatic melanoma.
Insights
Novel pH-sensitive nanomedicine carriers, lipid nanocapsules (LNCs), show enhanced melanoma cell uptake and efficacy. These modified LNCs overcome multidrug resistance (MDR) by targeting acidic tumor environments, improving cancer treatment potential.
Area of Science:
- Nanomedicine
- Oncology
- Materials Science
Background:
- Melanoma therapy faces challenges with low response rates and multidrug resistance (MDR).
- Decreased intratumoral pH exacerbates MDR and reduces anticancer drug sensitivity.
- Nanomedicines offer potential for delivering MDR-reversing agents and improving cancer treatment.
Purpose of the Study:
- To develop and evaluate novel pH-sensitive lipid nanocapsules (LNCs) for enhanced melanoma treatment.
- To engineer LNCs with copolymers for stealth properties and pH-responsive tumor cell entry.
- To investigate the efficacy of modified LNCs in overcoming chemoresistance.
Main Methods:
- Lipid nanocapsules (LNCs) were modified with N-vinylpyrrolidone (NVP) and vinyl imidazole (Vim) copolymers.
- The resulting P5 polymer-coated LNCs were characterized for pH-responsive charge transition.
- In vitro studies assessed cellular uptake under acidic conditions and biological effects, including opsonization resistance.
Main Results:
- P5-modified LNCs exhibited pH-responsive properties, transitioning from neutral to positive charge in acidic conditions.
- Enhanced cellular uptake was observed under acidic conditions, indicating improved tumor cell entry.
- P5 surface modification increased biological effect and protected nanocarriers from opsonization.
Conclusions:
- pH-sensitive LNCs demonstrate promising potential as nanocarriers for targeting metastatic melanoma.
- The developed nanomedicine effectively addresses chemoresistance associated with acidic tumor microenvironments.
- Surface modification with specific copolymers enhances LNC performance and therapeutic efficacy.
