A multifunctional magnetic nanosystem based on “two strikes” effect for synergistic anticancer therapy in triple-negative breast cancer

Zhang, Yu; Hu, Huiping; Tang, Wenqi; Zhang, Qian; Li, Ming; Huang, Jin; Huang, Zhen; Cui, Zheng; Xu, Jingya; Wang, Kaiping; Chen, Shi

doi:10.1016/j.jconrel.2020.03.036

Cited by 32 publications

(26 citation statements)

References 59 publications

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“…In other words, the amount of nanomedicine that can be effectively delivered to tumors and absorbed by tumor cells is pretty small, leading to a significant reduction in bioavailability. Previous studies have shown that the use of nanoparticle therapeutic media to respond to external stimuli (such as light, 14 pH, 15 enzymes, 16 magnetic field, 17 and temperature 18 ) can significantly improve antitumor efficacy. Quan et al designed a nanomedicine that responds to the highly expressed γ-glutamyl transpeptidase on the tumor cell surface, which can achieve high uptake and infiltration of distal tumor cells from the blood vessels.…”

Section: Introductionmentioning

confidence: 99%

Self-Monitoring and Self-Delivery of Self-Assembled Fluorescent Nanoparticles in Cancer Therapy

Li¹,

Yuan²,

Liu³

et al. 2021

IJN

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Due to the shortcomings of nanocarriers, the development of carrier-free nanodelivery systems has attracted more and more attention in cancer treatment. However, there are few studies on carrier-free nanosystems that can simultaneously achieve monitoring functions. Here a multifunctional carrier-free nanosystem loaded with curcumin and irinotecan hydrochloride was established for the treatment and monitoring of gastric cancer. Methods: In this study, an irinotecan hydrochloride-curcumin nanosystem in the early stage (the system is named SICN) was prepared. Based on the fluorescence of curcumin, flow cytometry, laser confocal microscopy, and zebrafish fluorescence imaging were used to study the monitoring function of SICN in vivo and in vitro. In addition, HGC-27 human gastric cancer cells were used to study SICN cytotoxicity. Results: Flow cytometry and zebrafish fluorescence imaging monitoring results showed that the uptake of SICN was significantly higher than free curcumin, and the excretion rate was lower. SICN had higher accumulation and retention in cells and zebrafish. Laser confocal microscopy monitoring results showed that SICN was internalized into HGC-27 cells through multiple pathways, including macropinocytosis, caveolin, and clathrin-mediated and clathrin -independent endocytosis, and distributed intracellularly throughout the whole cytoplasm, including lysosomes and Golgi apparatus. In vitro cell experiments showed that SICN nanoparticles were more toxic than single components, and HGC-27 cells had more absorption and higher toxicity to nanoparticles under slightly acidic conditions. Conclusion: SICN is a promising carrier-free nanoparticle, and the combination of two single-component therapies can exert a synergistic antitumor effect. When exposed to a tumor acidic environment, SICN showed stronger cytotoxicity due to charge conversion. More importantly, the nanoparticles' self-monitoring function has been developed, opening up new ideas for combined tumor therapy.

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Section: Introductionmentioning

confidence: 99%

Self-Monitoring and Self-Delivery of Self-Assembled Fluorescent Nanoparticles in Cancer Therapy

Li¹,

Yuan²,

Liu³

et al. 2021

IJN

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“…In-vitro targeting ability, cellular uptake and anti-tumor effect Hyaluronic acid, as a CD44 speci c ligand, is widely used in various targeted drug delivery systems for triple negative breast cancer [31,35]. The expression of CD44 on 4T1 cells was veri ed (Additional le 1, Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The CD44 expression level of 4T1 cells was evaluated by an inverted uorescence microscope (see Additional le 1, Methods 1.2 for details). The targeting test was performed using BNPs@Ptx, HA-BNPs@Ptx and HA-BNPs@Ptx with the cells in which CD44 receptor was presaturated by an excess amount of free HA [31]. To obtain stained nanoparticles, 1 mL BNPs@Ptx or HA-BNPs@Ptx suspensions were stained with 10 µL DiO (1:100).…”

Section: Cytotoxicity Assaymentioning

confidence: 99%

Synergistic Cascade Strategy Based on Modifying Tumor Microenvironment for Enhanced Breast Cancer Therapy

Zhang

Gao

et al. 2021

Preprint

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Background: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with very few treatment options. Although tumor-targeted nanomedicines hold great promise for the treatment of TNBC, the tumor microenvironment (TME) continues to be a major cause of failure in nanotherapy and immunotherapy. To overcome this barrier, we designed a new synergistic cascade strategy (SCS) that uses mild hyperthermia and smart drug delivery system (SDDS) to alter TME resistance in order to improve drug delivery and therapeutic efficacy of TNBC.Methods: Mild hyperthermia was produced by microwave (MW) irradiation. SDDS were formulated with thermosensitive polymer-lipid nanoparticles (HA-BNPs@Ptx), composed of polymer PLGA, phospholipid DPPC, hyaluronic acid (HA, a differentiation-44 targeted molecule, also known as CD44), 1-butyl-3-methylimidazolium-L-lactate (BML, a MW sensitizer) and paclitaxel (Ptx, chemotherapy drug). 4T1 breast tumor-bearing mice were treated with two-step MW combined with HA-BNPs@Ptx. Tumors in mice were pretreated with 1st MW irradiation prior to nanoparticle injection to modify TME and promote TME and promoting nanoparticle uptake and retention. The 2nd MW irradiation was performed on the tumor 24 h after the injection HA-BNPs@Ptx to produce a synergistic cascade effect through activating BML, thus enhancing hyperthermia effect, and instantly releasing Ptx at the tumor site.Results: Multifunctional CD44-targeted nanoparticles HA-BNPs@Ptx were successfully prepared and validated in-vitro. After the 1st MW irradiation of tumors in mice, the intratumoral perfusion increased by 2 times and the nanoparticle uptake augmented by 7 times. With the 2nd MW irradiation, remarkable anti-tumor effects were obtained with the inhibition rate up to 88%. In addition, immunohistochemical analysis showed that SCS therapy could not only promote the tumor cells apoptosis, trigger the immune response of cytotoxic T lymphocytes, but also significantly reduce the lung metastasis. Conclusions: The SCS using mild hyperthermia combined with smart drug delivery system, can significantly improve the efficacy of TNBC treatment in mice by modifying TME and hyperthermia-mediated EPR effects.

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“…Zhang et al, prepared multifunctional polymeric NPs (termed “HA‐Olb‐PPMNPs”) through coassembly of polyethylenimine–poly( d , l ‐lactide‐ co ‐glycolide) (PEI–PLGA), the anticancer drug olaparib (Olb), and Fe 3 O 4 NPs and then coated them with HA. [ 82 ] HA‐Olb‐PPMNPs presented superior cellular uptake ability and tumor aggregation efficiency based on the strong interaction between HA and CD44‐overexpressing triple negative breast cancer (TNBC). Moreover, T 2 ‐weighted MRI image results confirmed that HA‐Olb‐PPMNPs could serve as a T 2 contrast probe for the retention and diagnostics of tumors.…”

Section: Biomedical Applicationsmentioning

confidence: 99%

Functionalization of Magnetic Nanoparticles with Organic Ligands toward Biomedical Applications

Yang

Lee

2021

Advanced NanoBiomed Research

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Functionalization of magnetic nanoparticles (MNPs) with organic ligands to prepare personalized nanomedicine has attracted tremendous attention in biomedical applications. These organic/MNP nanohybrid platforms not only can exert the superparamagnetic property of MNPs for diagnosis imaging and treatment, but are also endowed with the merits of organic ligands for improved tumor‐targeting ability, blood circulation time, and cellular uptake. Flexibly manipulating the interactions between different inorganic ligands and MNPs to establish a single MNP matrix or multiple MNP assemblies presents advanced strategies in controlling their composition and chemical–physical and biological properties for various biomedical applications. Beginning with a brief introduction to a variety of strategies for the efficient functionalization of MNPs with various organic ligands, herein, the recent progress in the development and biomedical applications of the different types of nanoplatforms of organic ligand–mediated MNPs is briefly introduced, including diagnosis, therapy, imaging‐guided therapy, and drug delivery. Finally, the future opportunities and challenges for next‐generation high‐performance organic ligand–functionalized MNP nanoplatforms are also discussed.

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A multifunctional magnetic nanosystem based on “two strikes” effect for synergistic anticancer therapy in triple-negative breast cancer

Cited by 32 publications

References 59 publications

Self-Monitoring and Self-Delivery of Self-Assembled Fluorescent Nanoparticles in Cancer Therapy

Self-Monitoring and Self-Delivery of Self-Assembled Fluorescent Nanoparticles in Cancer Therapy

Synergistic Cascade Strategy Based on Modifying Tumor Microenvironment for Enhanced Breast Cancer Therapy

Functionalization of Magnetic Nanoparticles with Organic Ligands toward Biomedical Applications

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