Exploiting macrophages as targeted carrier to guide nanoparticles into glioma

Pang, Liang; Qin, Jing; Han, Limei; Zhao, Wenjie; Liang, Jianming; Xie, Zhongyi; Yang, Pei; Wang, Jianxin

doi:10.18632/oncotarget.9464

Cited by 120 publications

(89 citation statements)

References 45 publications

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“…[18,19] Increasing evidence indicates that the TAMs-based therapy is potentially effective. [20] Because of being potentially beneficial to tumor immunotherapy through polarizing macrophages, more and more attention was focused on how to promote the polarization of TAMs to M1 type. These agents including Fe 3 O 4 nanoparticles (NPs), [21] TLR3 agonist, [22] TLR7 agonist, [23] photosensitizer, [24] etc., have been reported to promote macrophage polarization in tumor tissue and produce certain tumor immunotherapy effect in vivo.…”

Section: The Progress Of Antitumor Immunotherapy Is Usually Limited Bmentioning

confidence: 99%

A Biomimetic Polymer Magnetic Nanocarrier Polarizing Tumor‐Associated Macrophages for Potentiating Immunotherapy

Liu

Wang

Guo

et al. 2020

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103

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The progress of antitumor immunotherapy is usually limited by tumor‐associated macrophages (TAMs) that account for the highest proportion of immunosuppressive cells in the tumor microenvironment, and the TAMs can also be reversed by modulating the M2‐like phenotype. Herein, a biomimetic polymer magnetic nanocarrier is developed with selectively targeting and polarizing TAMs for potentiating immunotherapy of breast cancer. This nanocarrier PLGA‐ION‐R837 @ M (PIR @ M) is achieved, first, by the fabrication of magnetic polymer nanoparticles (NPs) encapsulating Fe3O4 NPs and Toll‐like receptor 7 (TLR7) agonist imiquimod (R837) and, second, by the coating of the lipopolysaccharide (LPS)‐ treated macrophage membranes on the surface of the NPs for targeting TAMs. The intracellular uptake of the PIR @ M can greatly polarize TAMs from M2 to antitumor M1 phenotype with the synergy of Fe3O4 NPs and R837. The relevant mechanism of the polarization is deeply studied through analyzing the mRNA expression of the signaling pathways. Different from previous reports, the polarization is ascribed to the fact that Fe3O4 NPs mainly activate the IRF5 signaling pathway via iron ions instead of the reactive oxygen species‐induced NF‐κB signaling pathway. The anticancer effect can be effectively enhanced through potentiating immunotherapy by the polarization of the TAMs in the combination of Fe3O4 NPs and R837.

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Section: The Progress Of Antitumor Immunotherapy Is Usually Limited Bmentioning

confidence: 99%

A Biomimetic Polymer Magnetic Nanocarrier Polarizing Tumor‐Associated Macrophages for Potentiating Immunotherapy

Liu

Wang

Guo

et al. 2020

Small

103

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“…Fundamental understanding of the importance of monocytes and TAM in GBM has encouraged great interest in manipulating them for therapeutic purposes. Proofs have emerged for the concept of using monocytes and Mø as active carriers overcoming the BBB to deliver chemotherapy drugs in GBM [16,17]. Strategies to deplete TAM or modulate TAM phenotype and function have also shown therapeutic potential in the treatment of GBM [18,19].…”

Section: Introductionmentioning

confidence: 99%

Harnessing the Cross-talk between Tumor Cells and Tumor-associated Macrophages with a Nano-drug for modulation of Glioblastoma Immune Microenvironment

Wang

et al. 2017

Preprint

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Glioblastoma (GBM) is the most frequent and malignant brain tumor with a high mortality rate.The presence of a large population of macrophages (Mφ) in the tumor microenvironment is a prominent feature of GBM and these so-called tumor-associated Mφ (TAM) closely interact with the GBM cells to promote the survival, progression and therapy resistance of the GBM. Various therapeutic strategies have been devised either targeting the GBM cells or the TAM but few have addressed the cross-talks between the two cell populations. The present study was carried out to explore the possibility of exploiting the cross-talks between the GBM cells (GC) and TAM for modulation of the GBM microenvironment through using Nano-DOX, a drug composite based on nanodiamonds bearing doxorubicin. In the in vitro work on human cell models, Nano-DOXloaded TAM were first shown to be viable and able to infiltrate three-dimensional GC spheroids and release cargo drug therein. GC were then demonstrated to encourage Nano-DOX-loaded TAM to unload Nano-DOX back into GC which consequently emitted damage-associated molecular patterns (DAMPs) that are powerful immunostimulatory agents as well as indicators of cell damage. Nano-DOX was next proven to be a more potent inducer of GC DAMPs emission than doxorubicin. As a result, Nano-DOX-damaged GC exhibited an enhanced ability to attract both TAM and Nano-DOX-loaded TAM. Most remarkably, Nano-DOX-damaged GC reprogrammed the TAM from a pro-GBM phenotype to an anti-GBM phenotype that suppressed GC growth. Finally, the in vivo relevance of the in vitro findings was tested in animal study.Mice bearing orthotopic human GBM xenografts were intravenously injected with Nano-DOXloaded mouse TAM which were found releasing drug in the GBM xenografts 24 h after injection. GC damage was evidenced by the induction of DAMPs emission within the xenografts and a shift of TAM phenotype was detected as well. Taken together, our results demonstrate a novel way with therapeutic potential to harness the cross-talk between GBM cells and TAM for modulation of the tumor immune microenvironment.

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“…Особая роль макрофагов в прогрессировании опухоли была продемонстрирована в последние годы, и, основываясь на том, что макрофаги обладают свойством хоминга, позволяющим им мигрировать в опухолевые участки через ГЭБ в ответ на синтез цитокинов/хемокинов в пораженных тканях, Pang и др. использовали макрофаги в качестве «троянских коней» для переноса наночастиц с Dox для преодоления ГЭБ и высвобождения лекарства в местах опухоли головного мозга [29]. Dox был заключен в наночастицы, чтобы избежать повреждения клеток.…”

Section: обзор литературыunclassified

Nanoparticles: a New Approach to the Diagnosis and Treatment of Cerebral Glial Tumours

Gareev¹,

Beylerli²,

Павлов³

et al. 2019

Kreativnaâ hirurgiâ i onkologiâ

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Glial tumors, and in particular anaplastic astrocytomas and glioblastoma multiforme (GBM), are aggressive brain tumors with poor prognosis and high recurrence rates. Current treatment strategies are based on open surgery, chemotherapy and radiation therapy. However, not a single one of these methods of treatment, alone or in combination, is effective in combating this disease, resulting in the average life expectancy following the diagnosis of under 15 months. Treatments are inefficient mainly due to the blood-brain barrier (BBB) that makes the delivery of drugs into the tumor mass difficult. With the development of nanotechnology the effectiveness of the drugs currently in use is on an increase and the reach to glial brain tumors is expanding. Nanoparticles are a preferred carrier of medicinal agents and dyes due to their size, availability of surface modification and the flexibility enabling the integration of several functional components into a single system. This makes it possible to direct the development of nanoparticles towards applications in the treatment and diagnosis of glial tumors. This dual approach helps to understand the location of the tumor tissue, bio-distribution of nanoparticles, and treatment progress and effectiveness. In order to improve the treatment and diagnosis approaches, various strategies can be applied to modify the surface of nanoparticles, including surface markers or so-called ligands and use the characteristics of the tumor microenvironment with specific targets which respond to specific stimuli. In this paper we review various strategies for the improvement of treatment and diagnosis of glial tumors, describe some surface markers and talk about opportunities for the introduction of nanoparticles into everyday clinical practice.

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Exploiting macrophages as targeted carrier to guide nanoparticles into glioma

Cited by 120 publications

References 45 publications

A Biomimetic Polymer Magnetic Nanocarrier Polarizing Tumor‐Associated Macrophages for Potentiating Immunotherapy

A Biomimetic Polymer Magnetic Nanocarrier Polarizing Tumor‐Associated Macrophages for Potentiating Immunotherapy

Harnessing the Cross-talk between Tumor Cells and Tumor-associated Macrophages with a Nano-drug for modulation of Glioblastoma Immune Microenvironment

Nanoparticles: a New Approach to the Diagnosis and Treatment of Cerebral Glial Tumours

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