Chitosan-Decorated Doxorubicin-Encapsulated Nanoparticle Targets and Eliminates Tumor Reinitiating Cancer Stem-like Cells

Rao, Wei; Wang, Hai; Han, Jianfeng; Zhao, Shuting; Dumbleton, Jenna; Agarwal, Pranay; Zhang, Wujie; Zhao, Gang; Yu, Jianhua; Zynger, Debra L.; Lu, Xiongbin; He, Xiaoming

doi:10.1021/nn506928p

Cited by 255 publications

(189 citation statements)

References 58 publications

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“…74 A number of nanodelivery systems have been developed to target CD44 receptor using different targeting moieties (Table 6). [75][76][77][78] Besides anti-CD44 monoclonal antibodies, hyaluronic acid is also a popular ligand for CD44 targeting, as CD44 is a receptor of hyaluronic acid. 74 Other valuable targets of BCSC include CD133.…”

Section: Nanotherapy Of Breast Cancer Stem Cells (Bcscs)mentioning

confidence: 99%

Nanomedicine applications in the treatment of breast cancer: current state of the art

Xue

et al. 2017

IJN

158

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Breast cancer is the most common malignant disease in women worldwide, but the current drug therapy is far from optimal as indicated by the high death rate of breast cancer patients. Nanomedicine is a promising alternative for breast cancer treatment. Nanomedicine products such as Doxil ® and Abraxane ® have already been extensively used for breast cancer adjuvant therapy with favorable clinical outcomes. However, these products were originally designed for generic anticancer purpose and not specifically for breast cancer treatment. With better understanding of the molecular biology of breast cancer, a number of novel promising nanotherapeutic strategies and devices have been developed in recent years. In this review, we will first give an overview of the current breast cancer treatment and the updated status of nanomedicine use in clinical setting, then discuss the latest important trends in designing breast cancer nanomedicine, including passive and active cancer cell targeting, breast cancer stem cell targeting, tumor microenvironment-based nanotherapy and combination nanotherapy of drug-resistant breast cancer. Researchers may get insight from these strategies to design and develop nanomedicine that is more tailored for breast cancer to achieve further improvements in cancer specificity, antitumorigenic effect, antimetastasis effect and drug resistance reversal effect.

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Section: Nanotherapy Of Breast Cancer Stem Cells (Bcscs)mentioning

confidence: 99%

Nanomedicine applications in the treatment of breast cancer: current state of the art

Xue

et al. 2017

IJN

158

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“…2c). While the reasons for these localization behaviors are still largely unclear, it has previously been reported that chitosan can bind to CD44 receptors of cancer stem cells 161 and a similar receptor-mediated mechanism may be responsible where the neurites may present membrane receptors that can bind to starch. …”

Section: Location and Uptake Of Mnpsmentioning

confidence: 99%

Acute and Chronic Neural Stimulation via Mechano-Sensitive Ion Channels

Tay

2018

Springer Theses

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Neural stimulation techniques for eliciting calcium influx can elucidate the physiological roles of specific neural populations. To overcome some of the limitations of existing techniques such as poor specificity and noxious effects of heat, I developed a technology for non-invasive control of neural activities using magnetic forces and magnetic nanoparticles (MNPs) which offer deep tissue penetration and controllable dosage. Extensive investigations with different neurotoxins and experimental conditions support that the mechanism of magnetic stimulation that involves membrane-bound MNPs transducing magnetic forces into mechanical stretching of the cell membrane to enhance the opening probability of mechano-sensitive N-type calcium ion channels to induce calcium influx.Making use of the ability of neural networks to actively regulate their ratio of excitatory to inhibitory ion channel/receptor, I also performed chronic magnetic stimulation on fragile X iii syndrome (FXS) model neural networks. We found that chronic magnetic stimulation reduced the density of N-type calcium ion channels whose expression is increased in FXS. This technique demonstrates the potential of using bio-magnetic/mechanical forces to modulate expressions of mechano-sensitive ion channels where they are over-expressed in diseases such as abnormal nociception.Nonetheless, there are still a few areas where the technique can be improved. Firstly, it is the use of MNPs with more uniform properties to have greater control on magnetic stimulations.Secondly, the technique needs to be useful for in vivo studies. Therefore, I started researching on magnetotactic bacteria (MTB) which produce biological MNPs with superior properties such as uniform sizes and highly homogenous magnetic properties with the goal of harvesting MNPs from them.MTB, however, grow extremely slowly and the number of MNPs produced/bacterium is low. One way to overcome this problem is to evolve MTB over-producers of MNPs but this strategy is constrained by the absence of a selection platform that is quantitative and offer high throughput. To overcome this problem, I combined random chemical mutagenesis and selection using a magnetic ratcheting platform to generate and isolate MTB over-producers that produce twice as many MNPs/bacterium after 5 rounds of mutation/selection. I next designed a magnetic microfluidic device and demonstrate as a proof of concept, that it can be coupled to a bioreactor for high throughput microfluidic selection of MTB over-producers.iv

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“…For instance, Amiji's group developed a series of CD44-targeting HA-based self-assembling nanosystems for siRNA delivery and observed enhanced delivery efficiency and gene silencing activity of siRNA loaded in selected HA nanosystems in drug-resistant CD44 receptor-overexpressing tumour models [160]. Recently, they devised a nanodrug (nanodoxorubicin or nDOX) system by encapsulating DOX in nanoparticles synthesised using Pluronic F127 cross-linked and surface-decorated with chitosan, the chemical structure of which resembles that of HA [161]. The authors proved that nDOX significantly increased the cytotoxicity of doxorubicin in comparison to free doxorubicin for eliminating CD44 þ CSCs residing in 3D mammary tumour spheroids, and showed that nDOX could reduce the size of tumours in an orthotopic xenograft tumour model with no evident systemic toxicity (Fig.…”

Section: Application Of Targeted Nanocarriers For Csc Therapymentioning

confidence: 99%