Macrophages Actively Transport Nanoparticles in Tumors After Extravasation

Lin, Zachary P.; Nguyen, Luan N.; Ouyang, Ben; MacMillan, Presley; Ngai, Jessica; Kingston, Benjamin R.; Mladjenovic, Stefan M.; Chan, Warren C. W.

doi:10.1021/acsnano.1c11578

Cited by 51 publications

(32 citation statements)

References 39 publications

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“…Although this was observed for both NP sizes, only the animals administered with 60 nm NPs showed any significance ( p < 0.05). This size-dependent uptake of NPs by macrophages is in line with recent data, where it has been shown that smaller NPs are less internalized by CD11b + phagocytes compared to larger ones. In both cases, the lower levels of TAMs were still able to phagocytose significantly more NPs compared to the control ( p < 0.01).…”

Section: Resultssupporting

confidence: 91%

Gold Nanoparticle Delivery to Solid Tumors by Macrophage Depletion, Hypoxia Inhibition, and Collagen Degradation

Maksoudian

Izci

Salembier

et al. 2023

ACS Appl. Nano Mater.

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The delivery of nanomaterials (NMs) to solid tumors remains a heavily researched topic, and while significant efforts have been aimed at optimizing NM design for active tumor targeting, it has become clear that the aberrant and heterogeneous nature of the tumor microenvironment (TME) serves as a physical barrier to NM uptake by tumor cells. In our previous work, we show that NM delivery efficacy is dependent on NM size and is linked to various TME parameters, with the levels of tumorassociated macrophages (TAMs) and hypoxia, and density of the extracellular matrix (ECM) having the largest impact. In this study, we examined the effect of modulating these three components on the delivery of 20 and 60 nm gold nanoparticles (Au NPs) to the tumor in view of various TME parameters, including tumor size, necrosis, hypoxia, ECM density, blood vessel area and maturity, as well as different cell populations within the TME. While TAM depletion led to significant improvements in tumor vasculature maturity and coverage and increased NP uptake by cancer cells, it had no significant effect on overall NP delivery efficacy, possibly due to the failure of completely removing Kupffer cells. Additionally, reduction of hypoxia using acriflavine, a potent inhibitor of HIF-1α, was expected to improve NP delivery, but the results were also not significant. However, ECM breakdown using both acriflavine and collagenase led to significant improvements in NP delivery, especially for the larger NPs, although collagenase treatment alone resulted in increased tumor cell intravasation and metastasis. This study highlights the complexity and heterogeneity of the TME and the difficulties in optimizing NP delivery to solid tumors.

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Section: Resultssupporting

confidence: 91%

Gold Nanoparticle Delivery to Solid Tumors by Macrophage Depletion, Hypoxia Inhibition, and Collagen Degradation

Maksoudian

Izci

Salembier

et al. 2023

ACS Appl. Nano Mater.

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“…NPs with smaller sizes (15, 50, and 100 nm in this experiment) tended to diffuse for transport in the TME. [ 73 ] This study provides another possibility to reconsider the TAMs in the TME.…”

Section: Tumor Microenvironmentmentioning

confidence: 99%

Smart Nanoparticle‐Based Platforms for Regulating Tumor Microenvironment and Cancer Immunotherapy

Cheng

Santos

2022

Adv Healthcare Materials

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Tumor development and metastasis are closely related to the tumor microenvironment (TME). Recently, several studies indicate that modulating TME can enhance cancer immunotherapy. Among various approaches to modulating TME, nanoparticles (NPs) with unique inherent advantages and smart modified characteristics are promising candidates in delivering drugs to cancer cells, amplifying the therapeutic effects, and leading to a cascade of immune responses. In this review, several smart NP-based platforms are briefly introduced, such as responsive NPs, targeting NPs, and the composition of TME, including dendritic cells, macrophages, fibroblasts, endothelial cells, myeloid-derived suppressor cells, and regulatory T cells. Moreover, the recent applications of smart NP-based platforms in regulating TME and cancer immunotherapy are briefly introduced. Last, the advantages and disadvantages of these smart NP-based platforms in potential clinical translation are discussed.

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“…This is because plasma proteins (e.g., immunoglobulins, adhesion mediators, complement proteins) may act as opsonins to bind with the nanomaterials, leading to e cient phagocytosis by macrophages 36,41,42 . Considering the slow blood ow in the dense capillary network inside marrows 37,43 , the local macrophages take their time to capture nanoparticles and transport them to a distance from the vessels 44 .…”

Section: Resultsmentioning

confidence: 99%

Bone Disease Imaging through the Near-Infrared-II Window

Jin

Zhang

et al. 2023

Preprint

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Bone health related skeletal disorders are commonly diagnosed by X-ray imaging, but the radiation limits its use. Light excitation and optical imaging through the near-infrared-II window (NIR-II, 1000–1700 nm) can penetrate deep tissues without radiation risk, but the targeting of contrast agent is non-specific. Here, we report that lanthanide-doped nanocrystals can be passively transported by endothelial cells and macrophages from the blood vessels into bone marrow microenvironment. We found that this bone targeting scheme can be effective for longer than two months. We therefore developed an intravital 3D and high-resolution planar imaging instrumentation for bone disease diagnosis. We demonstrated the regular monitoring of 1 mm bone defects for 11 days in NIR-II window, with spatial resolution similar to X-ray imaging result, but more flexible use in prognosis. Moreover, the passive targeting can be used to reveal the early onset inflammation at the joints as the synovitis in the early stage of rheumatoid arthritis. Furthermore, the proposed method is comparable to micro computed tomography (µCT) in recognizing symptoms of osteoarthritis, including the mild hyperostosis in femur which is ~ 100 µm thicker than normal, and the growth of millimeter-scale osteophyte in the knee joint, which further proves the power and universality of our approach.

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Macrophages Actively Transport Nanoparticles in Tumors After Extravasation

Cited by 51 publications

References 39 publications

Gold Nanoparticle Delivery to Solid Tumors by Macrophage Depletion, Hypoxia Inhibition, and Collagen Degradation

Gold Nanoparticle Delivery to Solid Tumors by Macrophage Depletion, Hypoxia Inhibition, and Collagen Degradation

Smart Nanoparticle‐Based Platforms for Regulating Tumor Microenvironment and Cancer Immunotherapy

Bone Disease Imaging through the Near-Infrared-II Window

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