Promoting tumor penetration of nanoparticles for cancer stem cell therapy by TGF-β signaling pathway inhibition

Zuo, Zu-Qi; Chen, Kai-Ge; Yu, Xiaoyuan; Gui, Zhao; Shen, Song; Cao, Zhi-Ting; Luo, Ying-Li; Wang, Yucai; Wang, Jun

doi:10.1016/j.biomaterials.2015.12.014

Cited by 104 publications

(65 citation statements)

References 56 publications

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“…The commonly used 3D suspension culture was utilized to obtain mammospheres enriched with mammary CSCs [7,12,28,29]. Briefly, MDA-MB-231 and MCF-7 cells were cultured in 24-well ultralow attachment plates (Corning, Lowell, MA) at a density of 20,000 cells/ml in serum-free DMEM/F12-K supplemented with 5 μg/ml insulin, 20 ng/ml epidermal growth factor, 20 ng/ml basic fibroblast growth factor, 1x B27 (Invitrogen, Carlsbad, CA, USA), 0.4% (w/v) bovine serum albumin, 100 U/ml penicillin, and 100 μg/ml streptomycin.…”

Section: Methodsmentioning

confidence: 99%

Combined cancer therapy with hyaluronan-decorated fullerene-silica multifunctional nanoparticles to target cancer stem-like cells

et al. 2016

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Cancer stem-like cells (CSCs) are resistant to chemotherapy and highly tumorigenic, which contributes to tumor occurrence and post-treatment relapse. We developed a novel C60 fullerene-silica nanoparticle system surface-decorated with hyaluronan (HA) to target the variant CD44 overexpressed on breast CSCs. Furthermore, doxorubicin hydrochloride (DOX) and indocyanine green (ICG) can be encapsulated in the nanoparticles with ultrahigh encapsulation efficiency (> 90%) and loading content (e.g., 48.5% at a drug-to-nanoparticle feeding ratio of 1:1, compared to the commonly used drug-to-nanoparticle feeding ratio of 1:20 with a drug loading content of less than 5%). As a result, the DOX and ICG-laden nanoparticles can be used as a single nanoplatform to achieve combined chemo, photodynamic, and photothermal therapy under near infrared laser irradiation for effective destruction of the breast CSCs both in vitro and in vivo, with no evident systemic toxicity. Moreover, we found the nanoparticles with a higher drug loading content (e.g., 48.5 versus 4.6%) also have significantly higher antitumor efficacy, given the same total drug dose. These results demonstrate the great potential of the multifunctional hybrid nanoparticle system for augmenting cancer therapy by eliminating the CSCs.

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Section: Methodsmentioning

confidence: 99%

Combined cancer therapy with hyaluronan-decorated fullerene-silica multifunctional nanoparticles to target cancer stem-like cells

et al. 2016

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“…Recently, imatinib mesylate was found able to normalize the tumor microenvironment by inhibiting platelet‐derived growth factor receptor‐beta expression, tumor vessel normalization, and improving tumor perfusion . Disrupting tumor extracellular fibronectins by cyclopamine, depleting tumor collagen by losartan, inhibiting the expression of collagen I and TGF‐beta by pirfenidone, inhibiting the TGF‐beta signaling pathway by LY364947 and reducing tumor extracellular matrix by collagenase have been shown to significantly improve tumor perfusion and thereby nanomedicine accumulation and intratumoral distribution. For instance, cancer‐associated fibroblasts (CAFs), the major stromal cell type in the tumor microenvironment, play a key role in formation of the stromal barrier, leading to poor penetration for particulate therapeutics and even low perfusion for molecular drugs.…”

Section: Approaches To Achieve the 3s Transitionsmentioning

confidence: 99%

Rational Design of Cancer Nanomedicine: Nanoproperty Integration and Synchronization

et al. 2017

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Current cancer nanomedicines can only mitigate adverse effects but fail to enhance therapeutic efficacies of anticancer drugs. Rational design of next-generation cancer nanomedicines should aim to enhance their therapeutic efficacies. Taking this into account, this review first analyzes the typical cancer-drug-delivery process of an intravenously administered nanomedicine and concludes that the delivery involves a five-step CAPIR cascade and that high efficiency at every step is critical to guarantee high overall therapeutic efficiency. Further analysis shows that the nanoproperties needed in each step for a nanomedicine to maximize its efficiency are different and even opposing in different steps, particularly what the authors call the PEG, surface-charge, size and stability dilemmas. To resolve those dilemmas in order to integrate all needed nanoproperties into one nanomedicine, stability, surface and size nanoproperty transitions (3S transitions for short) are proposed and the reported strategies to realize these transitions are comprehensively summarized. Examples of nanomedicines capable of the 3S transitions are discussed, as are future research directions to design high-performance cancer nanomedicines and their clinical translations.

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“…CAFs also secrete high amount of TGF‐β to the TME (Farhood et al, ). Inhibition of TGF‐β signaling using LY364947 is reported to increase the rate of CSC penetration to nanoparticles facilitating CSC therapy (Zuo et al, ). Another example is that interaction between M2 cells (another key cells within the TME) favors release of STAT3 to the TME (Najafi, Hashemi Goradel et al, ) that further renders CSC immunosuppressive profile (D. Zhang et al, ) and induces radioresistance in the cells (Y. Shi et al, ).…”

Section: Csc Targeting In Cancer Therapymentioning

confidence: 99%

Cancer stem cells (CSCs) in cancer progression and therapy

Najafi

Farhood

Mortezaee

2018

Journal Cellular Physiology

393

268

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Cancer stem cells (CSCs) are self‐renewable cell types that are identified in most types of liquid and solid cancers and contributed to tumor onset, expansion, resistance, recurrence, and metastasis after therapy. CSCs are identified from the expression of cell surface markers, which is tumor‐type dependent. The transition between CSCs with cancer cells and other non‐CSCs occurs in cancers, which is possibly under the control of signals from CSCs and tumor microenvironment (TME), including CSC niche. Cancer‐associated fibroblasts are among the most influential cells for promoting both differentiation of CSCs and dedifferentiation of non‐CSCs toward attaining a CSC‐like phenotype. WNT/β‐catenin, transforming growth factor‐β, Hedgehog, and Notch are important signals for maintaining self‐renewal in CSCs. An effective therapeutic strategy relies on targeting both CSCs and non‐CSCs to remove a possible chance of tumor relapse. There are multiple ways to target CSCs, including immunotherapy, hormone therapy, (mi)siRNA delivery, and gene knockout. Such approaches can be designed for suppressing CSC stemness, tumorigenic cues from TME, CSC extrinsic and/or intrinsic signaling, hypoxia or for promoting differentiation in the cells. Because of sharing a range of characteristics to normal stem/progenitor cells, CSCs must be targeted based on their unique markers and their preferential expression of antigens.

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Promoting tumor penetration of nanoparticles for cancer stem cell therapy by TGF-β signaling pathway inhibition

Cited by 104 publications

References 56 publications

Combined cancer therapy with hyaluronan-decorated fullerene-silica multifunctional nanoparticles to target cancer stem-like cells

Combined cancer therapy with hyaluronan-decorated fullerene-silica multifunctional nanoparticles to target cancer stem-like cells

Rational Design of Cancer Nanomedicine: Nanoproperty Integration and Synchronization

Cancer stem cells (CSCs) in cancer progression and therapy

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