Aptamer-modified polymer nanoparticles for targeted drug delivery

Modrejewski, Julia; Walter, Johanna‐Gabriela; Kretschmer, Imme; Kemal, Evren; Green, Mark; Belhadj, Hamza; Blume, Cornelia; Scheper, Thomas

doi:10.1515/bnm-2015-0027

Cited by 16 publications

(5 citation statements)

References 31 publications

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“…Using confocal laser microscopy, we initially demonstrated the selective binding of S15-APT QDs to, and internalization into, A549 cells, while confirming that no binding and internalization occur in normal BEAS2B lung, CaCo-2, or HeLa cells (Figure 1A–1D ). The finding that S15-APT are taken up into A549 cells, but not into HeLa cells, is in accord with previous studies [ 11 , 24 ]; it was previously shown that neither squamous carcinoma NSCLC (NCI-H157), nor NSCLC (NCI-H446) and human breast carcinoma (MCF-7) cells exhibited any internalization of these S15-APT [ 11 ]. To confirm that the targeting properties are specifically attributable to the S15-APT, we undertook a competitive inhibition experiment with excess free S15-APTs (that are not conjugated to QDs), which completely abolished the binding to, and internalization of the S15-APT QDs into A549 cells (Figures 1E , 3B , and 3C ).…”

Section: Discussionsupporting

confidence: 91%

“…The S15-APT holds great potential as an attractive ligand to specifically target NSCLC [ 11 ]. Yet, this molecule was hardly investigated and little is known about its characteristics [ 24 ]. In the current paper, we studied the selectivity and specificity of S15-APT and investigated the mechanism underlying its internalization by target A549 cells.…”

Section: Discussionmentioning

confidence: 99%

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Cancer cell-selective, clathrin-mediated endocytosis of aptamer decorated nanoparticles

et al. 2018

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Lung cancer is the leading cause of cancer mortality worldwide, resulting in 88% deaths of all diagnosed patients. Hence, novel therapeutic modalities are urgently needed. Single-stranded oligonucleotide-based aptamers (APTs) are excellent ligands for tumor cell targeting. However, the molecular mechanisms underlying their internalization into living cells have been poorly studied. Towards the application of APTs for active drug targeting to cancer cells, we herein studied the mechanism underlying S15-APT internalization into human non-small cell lung cancer A549 cells. We thus delineated the mode of entry of a model nanomedical system based on quantum dots (QDs) decorated with S15-APTs as a selective targeting moiety for uptake by A549 cells. These APT-decorated QDs displayed selective binding to, and internalization by target A549 cells, but not by normal human bronchial epithelial BEAS2B, cervical carcinoma (HeLa) and colon adenocarcinoma CaCo-2 cells, hence demonstrating high specificity. Flow cytometric analysis revealed a remarkably low dissociation constant of S15-APTs-decorated QDs to A549 cells (Kd = 13.1 ± 1.6 nM). Through the systematic application of a series of established inhibitors of known mechanisms of endocytosis, we show that the uptake of S15-APTs proceeds via a classical clathrin-dependent receptor-mediated endocytosis. This cancer cell-selective mode of entry could possibly be used in the future to evade plasma membrane-localized multidrug resistance efflux pumps, thereby overcoming an important mechanism of cancer multidrug resistance.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Cancer cell-selective, clathrin-mediated endocytosis of aptamer decorated nanoparticles

et al. 2018

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“…21 However, one major limitation of PLA-NPs is that it cannot differentiate the cancerous cells from normal cells. Targeted drug delivery can be achieved by adding different groups and ligands, such as aptamers, 22,23 antibodies, 24,25 peptides 25,26 and vitamins 9,27,28 to nanoparticles. Meanwhile, small ligands of the vitamin molecule, such as folic acid, due to the fact that they do not significantly increase the size of the nanoparticle, as well as developing more stable connections with nanoparticles, are more noteworthy.…”

Section: Introductionmentioning

confidence: 99%

<p>Preparation and Evaluation of Doxorubicin-Loaded PLA–PEG–FA Copolymer Containing Superparamagnetic Iron Oxide Nanoparticles (SPIONs) for Cancer Treatment: Combination Therapy with Hyperthermia and Chemotherapy</p>

Khammarnia¹,

Nourbakhsh²,

Saber³

et al. 2020

IJN

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Background: Among the novel cancer treatment strategies, combination therapy is a cornerstone of cancer therapy. Materials and Methods: Here, combination therapy with targeted polymer, magnetic hyperthermia and chemotherapy was presented as an effective therapeutic technique. The DOX-loaded PLA-PEG-FA magnetic nanoparticles (nanocarrier) were prepared via a double emulsion method. The nanocarriers were characterized by particle size, zeta potential, morphology, saturation magnetizations and heat generation capacity, and the encapsulation efficiency, drug content and in-vitro drug release for various weight ratios of PLA:DOX. Then, cytotoxicity, cellular uptake and apoptosis level of nanocarrier-treated cells for HeLa and CT26 cells were investigated by MTT assay, flow cytometry, and apoptosis detection kit. Results and Conclusions: The synthesized nanoparticles were spherical in shape, had low aggregation and considerable magnetic properties. Meanwhile, the drug content and encapsulation efficiency of nanoparticles can be achieved by varying the weight ratios of PLA:DOX. The saturation magnetizations of nanocarriers in the maximum applied magnetic field were 59/447 emu/g and 28/224 emu/g, respectively. Heat generation capacity of MNPs and nanocarriers were evaluated in the external AC magnetic field by a hyperthermia device. The highest temperature, 44.2°C, was measured in the nanocarriers suspension at w/w ratio 10:1 (polymer:DOX weight ratio) after exposed to the magnetic field for 60 minutes. The encapsulation efficiency improved with increasing polymer concentration, since the highest DOX encapsulation efficiency was related to the nanocarriers' suspension at w/w ratio 50:1 (79.6 ± 6.4%). However, the highest DOX loading efficiency was measured in the nanocarriers' suspension at w/w ratio 10:1 (5.14 ± 0.6%). The uptake efficiency and apoptosis level of nanocarrier-treated cells were higher than those of nanocarriers (folic acid free) and free DOX-treated cells in both cell lines. Therefore, this targeted nanocarrier may offer a promising nanosystem for cancer-combined chemotherapy and hyperthermia.

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“…For drug delivery systems polymer nanoparticles are widely used . For example, polycaprolactone (PCL) has been used in combination with other polymers for many drug delivery systems . PCL is usually produced by ring‐opening polymerization of ε‐caprolactone .…”

Section: Introductionmentioning

confidence: 99%

Production of polycaprolactone nanoparticles with hydrodynamic diameters below 100 nm

Witt

Scheper

Walter

2019

Engineering in Life Sciences

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Cancer is a worldwide increasing burden and its therapy is often challenging and causes severe side effects in healthy tissue. If drugs are loaded into nanoparticles, side effects can be reduced, and efficiency can be increased via the enhanced permeability and retention effect. This effect is based on the fact that nanoparticles with sizes from 10 to 200 nm can accumulate in tumor tissue due to their leaky vasculature. In this work, we produced polycaprolactone (PCL) in the sizes 1.8, 5.4, and 13.6 kDa and were able to produce spherical shaped nanoparticles with mean diameters of 64 ± 19 nm out of the PCL5.4 and 45 ± 8 nm out of the PCL13.6 reproducibly. By encapsulation of paclitaxel the diameter of that nanoparticles did not increase, and we were able to encapsulate 73 ± 7 fmol paclitaxel per 1000 particles in the PCL5.4‐nanoparticles and 35 ± 8 fmol PTX per 1000 PCL13.6‐nanoparticles. Furthermore, we coupled the aptamer S15 to preformed PCL5.4‐nanoparticles resulting in particles with a hydrodynamic diameter of 153 nm. This offers the opportunity to use these nanoparticles for targeted drug delivery.

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Aptamer-modified polymer nanoparticles for targeted drug delivery

Cited by 16 publications

References 31 publications

Cancer cell-selective, clathrin-mediated endocytosis of aptamer decorated nanoparticles

Cancer cell-selective, clathrin-mediated endocytosis of aptamer decorated nanoparticles

<p>Preparation and Evaluation of Doxorubicin-Loaded PLA–PEG–FA Copolymer Containing Superparamagnetic Iron Oxide Nanoparticles (SPIONs) for Cancer Treatment: Combination Therapy with Hyperthermia and Chemotherapy</p>

Production of polycaprolactone nanoparticles with hydrodynamic diameters below 100 nm

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