Bromelain-Functionalized Multiple-Wall Lipid-Core Nanocapsules: Formulation, Chemical Structure and Antiproliferative Effect Against Human Breast Cancer Cells (MCF-7)

Oliveira, Catiúscia Padilha de; Prado, Willian Andrade; Lavayen, Vladimir; Büttenbender, Sabrina Laíz; Beckenkamp, Aline; Martins, Bruna S.; Lüdtke, Diogo S.; Campo, Leandra Franciscato; Rodembusch, Fabiano Severo; Buffon, Andréia; Pessoa, Adalberto; Guterres, Sílvia Stanisçuaski; Pohlmann, Adriana Raffin

doi:10.1007/s11095-016-2074-2

Cited by 37 publications

(29 citation statements)

References 48 publications

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“…Moreover, the lipid-core nanocapsules were developed using biocompatible and biodegradable materials and can be considered promising building blocks for the development of surface-functionalized nanoparticles. Indeed, we have recently proposed an innovative strategy to bind ligands on the surface of polymeric nanocapsules [ 23 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…Functionalization is based on the formation of an organometallic complex on the nanoparticle surface, using chitosan-coated lipid-core nanocapsules as nanocarriers, zinc (II), as metal ion and a molecule containing oxygen and/or nitrogen atoms, as ligand. The transition metal ion forms a chelate with chitosan and ligand on the nanoparticle surface [ 24 ]. We hypothesized that methotrexate, which contains amino acid functional groups, could be an effective ligand to functionalize the surface of those nanocapsules.…”

Section: Introductionmentioning

confidence: 99%

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Enhanced and Selective Antiproliferative Activity of Methotrexate-Functionalized-Nanocapsules to Human Breast Cancer Cells (MCF-7)

et al. 2018

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Methotrexate is a folic acid antagonist and its incorporation into nanoformulations is a promising strategy to increase the drug antiproliferative effect on human breast cancer cells by overexpressing folate receptors. To evaluate the efficiency and selectivity of nanoformulations containing methotrexate and its diethyl ester derivative, using two mechanisms of drug incorporation (encapsulation and surface functionalization) in the in vitro cellular uptake and antiproliferative activity in non-tumoral immortalized human keratinocytes (HaCaT) and in human breast carcinoma cells (MCF-7). Methotrexate and its diethyl ester derivative were incorporated into multiwall lipid-core nanocapsules with hydrodynamic diameters lower than 160 nm and higher drug incorporation efficiency. The nanoformulations were applied to semiconfluent HaCaT or MCF-7 cells. After 24 h, the nanocapsules were internalized into HaCaT and MCF-7 cells; however, no significant difference was observed between the nanoformulations in HaCaT (low expression of folate receptors), while they showed significantly higher cellular uptakes than the blank-nanoformulation in MCF-7, which was the highest uptakes observed for the drug functionalized-nanocapsules. No antiproliferative activity was observed in HaCaT culture, whereas drug-containing nanoformulations showed antiproliferative activity against MCF-7 cells. The effect was higher for drug-surface functionalized nanocapsules. In conclusion, methotrexate-functionalized-nanocapsules showed enhanced and selective antiproliferative activity to human breast cancer cells (MCF-7) being promising products for further in vivo pre-clinical evaluations.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Enhanced and Selective Antiproliferative Activity of Methotrexate-Functionalized-Nanocapsules to Human Breast Cancer Cells (MCF-7)

et al. 2018

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“…In parallel, we developed an innovative strategy to decorate the surface of the lipid-core nanocapsules by coating them with lecithin-chitosan and coordinating ligands at the surface by forming an organometallic complex using zinc-II or iron-II [ 32 ]. The new supramolecular structures were complexed by a quick and versatile non-covalent bound with different molecules, such as an antibody fragment anti-LDL(-), scFv-anti-LDL(-) [ 32 , 33 ] and enzymes, such as laronidase [ 34 ] as well as bromelain [ 35 ]. Taking into account the above mentioned, we hypothesis that our previous liquid formulation containing Dox-LNC could be surface functionalized using the chitosan-metal ion-ligand-complex interfacial reaction to improve the tumor targeting by using RGD as active targeting ligand.…”

Section: Introductionmentioning

confidence: 99%

Arginylglycylaspartic Acid-Surface-Functionalized Doxorubicin-Loaded Lipid-Core Nanocapsules as a Strategy to Target Alpha(V) Beta(3) Integrin Expressed on Tumor Cells

et al. 2017

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Doxorubicin (Dox) clinical use is limited by dose-related cardiomyopathy, becoming more prevalent with increasing cumulative doses. Previously, we developed Dox-loaded lipid-core nanocapsules (Dox-LNC) and, in this study, we hypothesized that self-assembling and interfacial reactions could be used to obtain arginylglycylaspartic acid (RGD)-surface-functionalized-Dox-LNC, which could target tumoral cells overexpressing αvβ3 integrin. Human breast adenocarcinoma cell line (MCF-7) and human glioblastoma astrocytoma (U87MG) expressing different levels of αvβ3 integrin were studied. RGD-functionalized Dox-LNC were prepared with Dox at 100 and 500 mg·mL−1 (RGD-MCMN (Dox100) and RGD-MCMN (Dox500)). Blank formulation (RGD-MCMN) had z-average diameter of 162 ± 6 nm, polydispersity index of 0.11 ± 0.04, zeta potential of +13.2 ± 1.9 mV and (6.2 ± 1.1) × 1011 particles mL−1, while RGD-MCMN (Dox100) and RGD-MCMN (Dox500) showed respectively 146 ± 20 and 215 ± 25 nm, 0.10 ± 0.01 and 0.09 ± 0.03, +13.8 ± 2.3 and +16.4 ± 1.5 mV and (6.9 ± 0.6) × 1011 and (6.1 ± 1.0) × 1011 particles mL−1. RGD complexation was 7.73 × 104 molecules per nanocapsule and Dox loading were 1.51 × 104 and 7.64 × 104 molecules per nanocapsule, respectively. RGD-functionalized nanocapsules had an improved uptake capacity by U87MG cells. Pareto chart showed that the cell viability was mainly affected by the Dox concentration and the period of treatment in both MCF-7 and U87MG. The influence of RGD-functionalization on cell viability was a determinant factor exclusively to U87MG.

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“…A few years ago, our research group proposed a new process to functionalize the surface of chitosan-coated lipid-core nanocapsules using a ligand-metal ion-chitosan-lecithin complex [27][28][29][30][31][32][33]. This method is based on a rapid one-pot synthesis without needing any purification step, overcoming the drawbacks of other methodologies.…”

Section: Introductionmentioning

confidence: 99%

“…More recently, we developed surface-functionalized nanocapsules using bromelain [31], a protease presenting antiproliferative effect. The enzyme maintained its proteolytic effect (in vitro) after immobilization on the nanocapsule surface; and when tested in vitro against human breast cancer cells (MCF-7), the bromelain-surface-functionalized nanocapsules showed a decrease on cell viability compared to the control.…”

Section: Introductionmentioning

confidence: 99%

Oral Treatment of Spontaneously Hypertensive Rats with Captopril-Surface Functionalized Furosemide-Loaded Multi-Wall Lipid-Core Nanocapsules

et al. 2020

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Multi-wall lipid-core nanocapsule (MLNC) functionalized with captopril and nanoencapsulating furosemide within the core was developed as a liquid formulation for oral administration. The nanocapsules had mean particle size below 200 nm, showing unimodal and narrow size distributions with moderate dispersity (laser diffraction and dynamic light scattering). Zeta potential was inverted from −14.3 mV [LNC-Fur(0,5)] to +18.3 mV after chitosan coating. Transmission electron microscopy and atomic force microscopy showed spherical structures corroborating the nanometric diameter of the nanocapsules. Regarding the systolic pressure, on the first day, the formulations showed antihypertensive effect and a longer effect than the respective drug solutions. When both drugs were associated, the anti-hypertensive effect was prolonged. On the fifth day, a time effect reduction was observed for all treatments, except for the nanocapsule formulation containing both drugs [Capt(0.5)-Zn(25)-MLNC-Fur(0.45)]. For diastolic pressure, only Capt(0.5)-Zn(25)-MLNC-Fur(0.45) presented a significant difference (p < 0.05) on the first day. On the fifth day, both Capt(0.5)-MLNC-Fur(0.45) and Capt(0.5)-Zn(25)-MLNC-Fur(0.45) had an effect lasting up to 24 h. The analysis of early kidney damage marker showed a potential protection in renal function by Capt(0.5)-Zn(25)-MLNC-Fur(0.45). In conclusion, the formulation Capt(0.5)-Zn(25)-MLNC-Fur(0.45) proved to be suitable for hypertension treatment envisaging an important innovation.

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Bromelain-Functionalized Multiple-Wall Lipid-Core Nanocapsules: Formulation, Chemical Structure and Antiproliferative Effect Against Human Breast Cancer Cells (MCF-7)

Abstract: 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.

Cited by 37 publications

References 48 publications

Enhanced and Selective Antiproliferative Activity of Methotrexate-Functionalized-Nanocapsules to Human Breast Cancer Cells (MCF-7)

Enhanced and Selective Antiproliferative Activity of Methotrexate-Functionalized-Nanocapsules to Human Breast Cancer Cells (MCF-7)

Arginylglycylaspartic Acid-Surface-Functionalized Doxorubicin-Loaded Lipid-Core Nanocapsules as a Strategy to Target Alpha(V) Beta(3) Integrin Expressed on Tumor Cells

Oral Treatment of Spontaneously Hypertensive Rats with Captopril-Surface Functionalized Furosemide-Loaded Multi-Wall Lipid-Core Nanocapsules

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