Hybrid Lipid Polymer Nanoparticles for Combined Chemo- and Photodynamic Therapy

Abstract

Retinoblastoma is a malignant tumor of the retina in infants. Conventional therapies are associated to severe side effects and some of them induce secondary tumors. Photodynamic therapy (PDT) thus appears as a promising alternative as it is nonmutagenic and generates minimal side effects. The effectiveness of PDT requires the accumulation of a photosensitizer (PS) in the tumor. However, most porphyrins are hydrophobic and aggregate in aqueous medium. Their incorporation into a nanocarrier may improve their delivery to the cell cytoplasm. In this work, we designed biodegradable liponanoparticles (LNPs) consisting of a poly(D,L)-lactide (PDLLA) nanoparticle coated with a phospholipid (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine/1,2-dioleoyl-3-trimethylammonium-propane) bilayer. An anticancer drug, beta-lapachone (β-Lap) and a PS, m-THPC, were co-encapsulated for combined chemo-and PDT because it has been suggested that they may have a synergistic effect based on the activation of β-Lap by PDTinduced over-expression of the enzyme NQO1. Using dynamic light scattering measurements, cryogenic transmission electron microscopy, and fluorescence confocal microscopy, we selected the appropriate conditions for the encapsulation of the compounds. LNPs were internalized in retinoblastoma cells within few hours. No obvious synergistic effect related to the activation of β-Lap by PDT was observed. Conversely, the LNPs were cytotoxic at lower doses of the two encapsulated compounds as compared to the single therapies. Analysis of the combinatorial treatment showed that PDT and chemotherapy had an additive effect on the viability of retinoblastoma cells.

Scratching the Surface (Modification): Developing a Quantitative Liquid Chromatography–Tandem Mass Spectrometry Method for the Investigation of PEGylated and Non-PEGylated Lipid Mixtures on Lipid-Coated Lanthanide Nanoparticles

“…Assuming a minimum 100-fold dilution, this means that <1 μg of total lipid material is required for lipid analysis using this LC-MS/MS method. This is substantially less sample than that required for 1 H NMR 41 or LC-MS 11 analysis of lipid coatings (∼1 mg).…”

“…In this way, hydrophilic NPs can be coated with lipid bilayers, , and hydrophobic NPs can be coated with lipid monolayers. , Additionally, very small hydrophobic NPs can be encapsulated within the walls of liposomes . Lipid-coated NPs have been employed in siRNA and drug delivery, − photodynamic therapy, cellular imaging, and sensing . Our group is interested in using lipid-coated lanthanide (Ln) NPs of the general formula NaLnF 4 as potential high-sensitivity mass tags for applications in mass cytometry and imaging mass cytometry (Fluidigm). , …”

“…The authors showed that when 10 mol % DPPE-PEG was used in the formulation, the amount of DPPE-PEG in the lipid coating on the NPs was only in the range of 2−3 mol % for PEGs with molecular weights of 750, 2000, and 5000 g/mol. N'Diaye et al 11 used high-performance liquid chromatography (HPLC) with evaporative light scattering detection to monitor the lipids extracted from PLA NPs coated with a mixture of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP). They found that the amount of lipid per NP increased with a decrease in (cationic) DOTAP concentration, and that the final composition included more DOTAP than in the original lipid formulation.…”

Utilization of Polymer-Lipid Hybrid Nanoparticles for Targeted Anti-Cancer Therapy

“…Diaye et al designed a chemotherapeutic drug beta-lapachone (β-Lap) and photosensitizer m-THPC co-loaded in a different area of the biodegradable PLHNP system for the treatment of retinoblastoma malignant tumor. This hybrid carrier can be used for combined chemo-phototherapy in both oxygenated and hypoxia tumor tissues via single IV injection and concurrent phototherapy induced the expression of NQO1 in Y79 cells, offering a better therapeutic strategy for malignant tumors [ 132 ]. Another study reported improved therapeutic efficacy of combined photothermal-chemotherapy by polyaniline-lipid hybrid NPs.…”

Biotinylated Lipid-Coated NaLnF4 Nanoparticles: Demonstrating the Use of Lanthanide Nanoparticle-Based Reporters in Suspension and Imaging Mass Cytometry

“…Lipid bilayer encapsulation of NPs has been the most successful for mesoporous silica NPs , or silica-coated NPs but has also been reported for NPs composed of gold, , calcium phosphate, titanium oxide, and polymers including poly­(lactic- co -glycolic acid), , polystyrene, , and polylactic acid. − We are aware of only a few examples in the literature of lipid bilayer-coated LnNPs. One should note that the lipid bilayer examples discussed here are in contrast to examples in which a monolayer of lipids forms a bilayer with the oleic acid ligands on the LnNP surface.…”