Doxorubicin-loaded micelles with high drug-loading capacity and stability based on zwitterionic oligopeptides

Xue, Weili; Trital, Ashish; Liu, Sihang; Xu, Liangbo

doi:10.1039/d0nj02785e

Cited by 8 publications

(5 citation statements)

References 39 publications

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“…As displayed in Figure D, the particle size distribution histogram displayed that the average particle size of PPIMYRC–DOX micelles was 21.5 nm, which proved that PPIMYRC–DOX micelles had small particle size and narrower particle size distribution. Spherical structure facilitated penetration and enrichment of micelles at tumor sites . The TEM characterization showed that PPIMYRC–DOX micelles had the potential to be enriched in the tumor site through the EPR effect …”

Section: Resultsmentioning

confidence: 99%

“…Spherical structure facilitated penetration and enrichment of micelles at tumor sites. 41 The TEM characterization showed that PPIMYRC−DOX micelles had the potential to be enriched in the tumor site through the EPR effect. 42 The ζ potential and hydrodynamic size played an important role in nano-drug delivery.…”

Section: Characterization Of Ppimyrc−dox Micellesmentioning

confidence: 99%

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Zwitterionic Targeting Doxorubicin -Loaded Micelles Assembled by Amphiphilic Dendrimers with Enhanced Antitumor Performance

et al. 2023

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Chemotherapy is the main method of treating malignant tumors in clinical treatment. However, the commonly used chemotherapeutic drugs have the disadvantages of high biological toxicity, poor water solubility, low targeting ability, and high side effects. Zwitterionic micelles assembled by amphiphilic dendrimers modified with zwitterionic groups and targeting ligand should largely overcome these shortcomings. Herein, the zwitterionic group and targeting peptide c(RGDfC) were modified on the surface of generation 2 poly(propylene imine) dendrimers (G2 PPI), which was conjugated with hydrophobic N-(2-mercaptoethyl) oleamide to form amphiphilic dendrimers (PPIMYRC). PPIMYRC self-assembled into micelles with doxorubicin (DOX) loaded in the interior of micelles to prepare DOX-loaded micelles (PPIMYRC−DOX micelles). The PPIMYRC−DOX micelles had great stability in fibrinogen and pH-responsive drug release. Furthermore, PPIMYRC−DOX micelles had higher cellular uptake rates than free DOX, resulting in higher cytotoxicity of PPIMYRC−DOX micelles than that of free DOX. More importantly, PPIMYRC−DOX micelles inhibited tumors much better than free DOX. The tumor inhibition rate of PPIMYRC−DOX micelles was as high as 93%. Taken together, PPIMYRC−DOX micelles were assembled by amphiphilic dendrimers with the zwitterionic and targeting groups, which enhanced the therapeutic effect of DOX and reduced its side effects. The prepared targeting nanodrug has great potential for further application in antitumor therapy.

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Section: Resultsmentioning

confidence: 99%

Section: Characterization Of Ppimyrc−dox Micellesmentioning

confidence: 99%

Zwitterionic Targeting Doxorubicin -Loaded Micelles Assembled by Amphiphilic Dendrimers with Enhanced Antitumor Performance

et al. 2023

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“…Doxorubicin (DOX) is effective against tumor cells, but the systemic application of this drug usually causes severe side effects in other tissues, such as irreversible cardiotoxicity or nephrotoxicity. Therefore, the clinical application of DOX has been limited [ 1 , 2 , 3 ]. How to effectively deliver drugs to tumor cells in a targeted manner is one of the key issues in the treatment of cancer.…”

Section: Introductionmentioning

confidence: 99%

A Cationic Amphiphilic AIE Polymer for Mitochondrial Targeting and Imaging

Zhou

Wang

et al. 2022

Pharmaceutics

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Mitochondria are important organelles that play key roles in generating the energy needed for life and in pathways such as apoptosis. Direct targeting of antitumor drugs, such as doxorubicin (DOX), to mitochondria into cells is an effective approach for cancer therapy and inducing cancer cell death. To achieve targeted and effective delivery of antitumor drugs to tumor cells, to enhance the therapeutic effect, and to reduce the side effects during the treatment, we prepared a cationic amphiphilic polymer with aggregation-induced emission (AIE) characteristic. The polymer could be localized to mitochondria with excellent organelle targeting, and it showed good mitochondrial targeting with low toxicity. The polymer could also self-assemble into doxorubicin-loaded micelles in phosphate buffer, with a particle size of about 4.3 nm, an encapsulation rate of 11.03%, and micelle drug loading that reached 0.49%. The results of in vitro cytotoxicity experiments showed that the optimal dosage was 2.0 μg/mL, which had better inhibitory effect on tumor cells and less biological toxicity on heathy cells. Therefore, the cationic amphiphilic polymer can partially replace expensive commercial mitochondrial targeting reagents, and it can be also used as a drug loading tool to directly target mitochondria in cells for corresponding therapeutic research.

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“…PEGylation, the most popular way for surface protection, shows the opposite effect in different steps, which improves nanodrug accumulation in tumors by enhanced permeability and retention effect (EPR) , but impedes the penetration into the depths of tumors and the internalization rate by tumor cells. − On the other hand, cell-membrane-originated nanodrugs show good capabilities in CAPIR through biomimicking while they are rather difficult for large-scale commercialization. − Recently, negative-charge-biased zwitterionic polymer-protected nanodrugs, which mimic serum globulin surface or cell membrane, also showed long blood circulation, efficient accumulation at the tumor site, fast tumor tissue penetration, and tumor cell internalization, as well as efficient drug release in the cells, thereby highly inhibiting tumor growth. − Such efficient tumor targeting is mainly caused by the high resistance to nonspecific protein adsorption, or so-called “stealth” in blood, , diffusion-preferred liquification of gelated water molecules in tumor extracellular matrix (ECM) by the “salt” effect of zwitterionic groups, and the instant affinity transition in slightly acidic TME . However, only little is known about the size effect on zwitterionic polymer-protected nanodrugs since previous zwitterionic nanodrugs were difficult to control the size without changing the molecular structure.…”

Section: Introductionmentioning

confidence: 99%

Size Effect of Zwitterionic Peptide-Based Nanoscale Micelles on Cancer Therapy

Wei

Xue

et al. 2022

ACS Appl. Nano Mater.

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Negative-charge-biased zwitterionic nanodrugs showed "stealthy" in blood circulation and "sticky" to sialic acid abundant tumor cells in the tumor microenvironment (TME), thereby prolonging blood circulation, increasing tumor targeting, and reducing accumulation in healthy liver and kidney. However, the correlation between the particle size, one of the crucial parameters of these nanodrugs, and their interactions with biological systems is unclear. Here, KEKDCDEKE (EK9) small peptide was used to replace zwitterionic polypeptides to prepare doxorubicin (DOX)-conjugated nanodrugs with well-controlled size, which is, respectively, 30, 60, and 90 nm diameter, for investigating the size effect on cancer therapy. Results showed that the size increase of these zwitterionic nanodrugs improves their blood circulation and retention in tumor but reduces the internalization rate and tumor tissue penetration, although all nanodrugs were self-assembled by the same conjugates. There is an optimal particle size, 60 nm in this work, for the zwitterionic nanodrugs to balance these effects, thereby improving their ability to inhibit tumor growth. These findings suggest that the particle size of zwitterionic nanodrugs also plays a particularly important role in controlling the behaviors of zwitterionic peptide-based nanodrugs.

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Doxorubicin-loaded micelles with high drug-loading capacity and stability based on zwitterionic oligopeptides

Abstract:
To simplify preparation process and increase the drug-loading capacity of antitumor nanodrugs, doxorubicin-loaded micelles based on zwitterionic oligopeptides were fabricated through two step reactions in mild conditions. Zwitterionic oligopeptides Glu-Lys-Cys-Glu-Lys...

Cited by 8 publications

References 39 publications

Zwitterionic Targeting Doxorubicin -Loaded Micelles Assembled by Amphiphilic Dendrimers with Enhanced Antitumor Performance

Zwitterionic Targeting Doxorubicin -Loaded Micelles Assembled by Amphiphilic Dendrimers with Enhanced Antitumor Performance

A Cationic Amphiphilic AIE Polymer for Mitochondrial Targeting and Imaging

Size Effect of Zwitterionic Peptide-Based Nanoscale Micelles on Cancer Therapy

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Doxorubicin-loaded micelles with high drug-loading capacity and stability based on zwitterionic oligopeptides

Abstract: To simplify preparation process and increase the drug-loading capacity of antitumor nanodrugs, doxorubicin-loaded micelles based on zwitterionic oligopeptides were fabricated through two step reactions in mild conditions. Zwitterionic oligopeptides Glu-Lys-Cys-Glu-Lys...

Cited by 8 publications

References 39 publications

Zwitterionic Targeting Doxorubicin -Loaded Micelles Assembled by Amphiphilic Dendrimers with Enhanced Antitumor Performance

Zwitterionic Targeting Doxorubicin -Loaded Micelles Assembled by Amphiphilic Dendrimers with Enhanced Antitumor Performance

A Cationic Amphiphilic AIE Polymer for Mitochondrial Targeting and Imaging

Size Effect of Zwitterionic Peptide-Based Nanoscale Micelles on Cancer Therapy

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Product

Resources

About

Abstract:
To simplify preparation process and increase the drug-loading capacity of antitumor nanodrugs, doxorubicin-loaded micelles based on zwitterionic oligopeptides were fabricated through two step reactions in mild conditions. Zwitterionic oligopeptides Glu-Lys-Cys-Glu-Lys...