Bromelain-Functionalized Multiple-Wall Lipid-Core Nanocapsules: Formulation, Chemical Structure and Antiproliferative Effect Against Human Breast Cancer Cells (MCF-7)
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This study was conducted a promising approach to surface functionalization developed for lipid-core nanocapsules and the merit to pursue new strategies to treat solid tumors.
Bromelain-functionalized multiple-wall lipid-core nanocapsules (Bro-MLNC-Zn) were produced by self-assembling following three steps of interfacial reactions. Physicochemical and structural characteristics, in vitro proteolytic activity (casein substrate) and antiproliferative activity (breast cancer cells, MCF-7) were determined.
Bro-MLNC-Zn had z-average diameter of 135 nm and zeta potential of +23 mV. The complex is formed by a Zn-N chemical bond and a chelate with hydroxyl and carboxyl groups. Bromelain complexed at the nanocapsule surface maintained its proteolytic activity and showed anti-proliferative effect against human breast cancer cells (MCF-7) (72.6 ± 1.2% at 1.250 μg mL−1 and 65.5 ± 5.5% at 0.625 μg mL−1). Comparing Bro-MLNC-Zn and bromelain solution, the former needed a dose 160-folds lower than the latter for a similar effect. Tripan blue dye assay corroborated the results.
The surface functionalization approach produced an innovative formulation having a much higher anti-proliferative effect than the bromelain solution, even though both in vitro proteolytic activity were similar, opening up a great opportunity for further studies in nanomedicine.
KEY WORDSbromelain lipid-core nanocapsules MCF-7 human breast cancer cells metal-chitosan complex surface-functionalized nanoparticles
One-way analysis of variance
Acridine orange base
Bromelain-functionalized multiple-wall lipid-core nanocapsules
Center of Nanoscience and Nanotechnology at the Federal University of Rio Grande do Sul
Particle diameter at percentile 90 under the particle size distribution curves
Dulbecco’s modified Eagle’s medium
Fetal bovine serum
Human epidermal growth factor receptor
Cationic lipid-core nanocapsules/lecithin-chitosan-polysorbate 80-coated lipid-core nanocapsules
Lecithin-polysorbate 80-coated lipid-core nanocapsules
- log D
Multi-wall lipid-core nanocapsules
Mammalian target of rapamycin
Nanoparticle tracking analysis
Rhodamine B-poly(ε-caprolactone) conjugate
Phenylalanine-functionalized multi-wall lipid-core nanocapsules
Particle number density
Transmission electron microscopy
ACKNOWLEDGMENTS AND DISCLOSURES
Catiúscia Padilha de Oliveira and Willian Andrade de Prado thanks the Brazilian Agency CAPES for their fellowships. The authors thank the Grants from Brazilian Agencies: CNPq/Brasilia/Brazil, CAPES/MEC and FAPERGS. The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. Catiúscia P. Oliveira and Willian A. Prado contributed equally. The authors report no conflicts of interest in this work.
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