CD44 targeted redox-triggered self-assembly with magnetic enhanced EPR effects for effective amplification of gambogic acid to treat triple-negative breast cancer

Sang, Mangmang; Han, Lu; Luo, Renjie; Qu, Wei; Zheng, Feng; Zhang, Kaigang; Liu, Fulei; Xue, Jingwei; Liu, Wenyuan; Feng, Feng

doi:10.1039/c9bm01171d

Cited by 42 publications

(24 citation statements)

References 37 publications

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“…Sang and coworkers produced polymeric micelles that contained iron oxide nanoparticles and were functionalized with hyaluronic acid (which can target the CD44 receptor). After application of the magnetic field, these particles exhibited significantly stronger affinity and intercellular penetration of 4T1 cancer cells than the control [58]. Effective targeting was also observed during in vivo imaging of tumorbearing mice after intravenous injection of these magnetic nanoparticles and exposure to a magnetic field [58].…”

Section: Discussionmentioning

confidence: 79%

Hyperthermia treatment of cancer cells by the application of targeted silk/iron oxide composite spheres

Kucharczyk

Kaczmarek

Józefczak

et al. 2021

Materials Science and Engineering: C

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Magnetic iron oxide nanoparticles (IONPs) are one of the most extensively studied materials for theranostic applications. IONPs can be used for magnetic resonance imaging (MRI), delivery of therapeutics, and hyperthermia treatment. Silk is a biocompatible material and can be used for biomedical applications. Previously, we produced spheres made of H2.1MS1 bioengineered silk that specifically carried a drug to the Her2-overexpressing cancer cells. To confer biocompatibility and targeting properties to IONPs, we blended these particles with bioengineered spider silks.Three bioengineered silks (MS1Fe1, MS1Fe2, and MS1Fe1Fe2) functionalized with the adhesion peptides F1 and F2, were constructed and investigated to form the composite spheres with IONPs carrying a positive or negative charge. Due to its highest IONP content, MS1Fe1 silk was used to produce spheres from the H2.1MS1:MS1Fe silk blend to obtain a carrier with cell-targeting properties. Composite H2.1MS1:MS1Fe1/IONP spheres made of silks blended at different ratios were obtained. Although the increased content of MS1Fe1 silk in particles resulted in an increased affinity of the spheres to IONPs, it decreased the binding of the composite particles to cancer cells. The H2.1MS1:MS1Fe1 particles prepared at a ratio of 8:2 and loaded with IONPs exhibited the ability to bind to the targeted cancer cells similar to the control spheres without IONPs. Moreover, when exposed to the alternating magnetic field, these particles generated 2.5 times higher heat. They caused an almost three times higher percentage of apoptosis in cancer cells than the control particles.The blending of silks enabled the generation of cancer-targeting spheres with a high affinity for iron oxide nanoparticles, which can be used for anti-cancer hyperthermia therapy.

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Section: Discussionmentioning

confidence: 79%

Hyperthermia treatment of cancer cells by the application of targeted silk/iron oxide composite spheres

Kucharczyk

Kaczmarek

Józefczak

et al. 2021

Materials Science and Engineering: C

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“…Sang et al developed a GA drug nanoconjugate with an outer layer made up of mono-aminated poly (ethylene glycol)-grafted hyaluronic acid that can specifically target CD44 receptors on TNBC (Hyaluronic acid has higher affinity to bind CD44 on TNBC); the middle layer comprises disulfide-linked hexadecanol (Hex) as well as chitosan oligosaccharide (CSO) that controls the drug release, while the core layer is made up of SPIONs attached to GA that can increase the enhanced permeation and retention effect due to magnetic focusing. This complex of mPEG-HA/CSO-SS-Hex/SPION/GA nanosystem led to efficient delivery of the drug using magnetic guidance to focus in TNBC microenvironment [200].…”

Section: (I) Quantum Dots (Qd)mentioning

confidence: 99%

Triple-Negative Breast Cancer: A Review of Conventional and Advanced Therapeutic Strategies

Medina

Oza

Sharma

et al. 2020

IJERPH

222

164

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Triple-negative breast cancer (TNBC) cells are deficient in estrogen, progesterone and ERBB2 receptor expression, presenting a particularly challenging therapeutic target due to their highly invasive nature and relatively low response to therapeutics. There is an absence of specific treatment strategies for this tumor subgroup, and hence TNBC is managed with conventional therapeutics, often leading to systemic relapse. In terms of histology and transcription profile these cancers have similarities to BRCA-1-linked breast cancers, and it is hypothesized that BRCA1 pathway is non-functional in this type of breast cancer. In this review article, we discuss the different receptors expressed by TNBC as well as the diversity of different signaling pathways targeted by TNBC therapeutics, for example, Notch, Hedgehog, Wnt/b-Catenin as well as TGF-beta signaling pathways. Additionally, many epidermal growth factor receptor (EGFR), poly (ADP-ribose) polymerase (PARP) and mammalian target of rapamycin (mTOR) inhibitors effectively inhibit the TNBCs, but they face challenges of either resistance to drugs or relapse. The resistance of TNBC to conventional therapeutic agents has helped in the advancement of advanced TNBC therapeutic approaches including hyperthermia, photodynamic therapy, as well as nanomedicine-based targeted therapeutics of drugs, miRNA, siRNA, and aptamers, which will also be discussed. Artificial intelligence is another tool that is presented to enhance the diagnosis of TNBC.

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“…To improve the targetability of NP-loaded drug complexes, Seng et al reported dualtargeted redox-responsive hybrid polymeric micelles functionalized with HA to improve the delivery efficiency of an NP-loaded anticancer drug, Gambogic acid (GA) [135]. A self-assembled nanosystem composed of an outer layer of PEGylated HA for targeting the CD-44 receptor, reduction-responsive disulfide-linked hexadecanol (HEX), chitosan (CHO), and superparamagnetic iron oxide nanoparticles (SPION) as a core to load GA.…”

Section: Cd-44 Targeted Drug-loaded Npsmentioning

confidence: 99%

“…There was a 88% reduction in the tumor volume for mPEG-HA/CHO-SS-HEX-SPION-GA with MF compared to free GA formulations. A biodistribution and toxicity study with the nano-formulation revealed extended concentrations of the drug in plasma without any notable toxicity [135].…”

Section: Cd-44 Targeted Drug-loaded Npsmentioning

confidence: 99%

Nanoparticles Targeting Receptors on Breast Cancer for Efficient Delivery of Chemotherapeutics

2021

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The journey of chemotherapeutic drugs from the site of administration to the site of action is confronted by several factors including low bioavailability, uneven distribution in major organs, limited accessibility of drug molecules to the distant tumor tissues, and lower therapeutic indexes. These unavoidable features of classical chemotherapeutics necessitate an additional high, repetitive dose of drugs to obtain maximum therapeutic responses with the result of unintended adverse side effects. An erratic tumor microenvironment, notable drawbacks of conventional chemotherapy, and multidrug-resistant mechanisms of breast cancer cells warrant precisely designed therapeutics for the treatment of cancers. In recent decades, nanoparticles have been deployed for the delivery of standard anticancer drugs to maximize the therapeutic potency while minimizing the adverse effects to increase the quality and span of life. Several organic and inorganic nanoplatforms that have been designed exploiting the distinctive features of the tumor microenvironment and tumor cells offer favorable physicochemical properties and pharmacokinetic profiles of a parent drug, with delivery of higher amounts of the drug to the pathological site and its controlled release, thereby improving the balance between its efficacy and toxicity. Advances to this front have included design and construction of targeted nanoparticles by conjugating homing devices like peptide, ligand, and Fab on the surface of nanomaterials to navigate nanoparticledrug complexes towards the target tumor cell with minimal destruction of healthy cells. Furthermore, actively targeting nanoparticles can facilitate the delivery and cellular uptake of nanoparticle-loaded drug constructs via binding with specific receptors expressed aberrantly on the surface of a tumor cell. Herein, we present an overview of the principle of targeted delivery approaches, exploiting drug-nanoparticle conjugates with multiple targeting moieties to target specific receptors of breast cancer cells and highlighting therapeutic evaluation in preclinical studies. We conclude that an understanding of the translational gap and challenges would show the possible future directions to foster the development of novel targeted nanotherapeutics.

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CD44 targeted redox-triggered self-assembly with magnetic enhanced EPR effects for effective amplification of gambogic acid to treat triple-negative breast cancer

Abstract: Scheme of mPEG-HA/CSO-SS-Hex/SPION/GA self-assembly preparation and the magnetism-enhanced EPR in vivo and in vitro trafficking pathways of the polymeric self-assembly.

Cited by 42 publications

References 37 publications

Hyperthermia treatment of cancer cells by the application of targeted silk/iron oxide composite spheres

Hyperthermia treatment of cancer cells by the application of targeted silk/iron oxide composite spheres

Triple-Negative Breast Cancer: A Review of Conventional and Advanced Therapeutic Strategies

Nanoparticles Targeting Receptors on Breast Cancer for Efficient Delivery of Chemotherapeutics

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