Low dose gemcitabine-loaded lipid nanocapsules target monocytic myeloid-derived suppressor cells and potentiate cancer immunotherapy

Sasso, Maria Stella; Lollo, Giovanna; Pitorre, Marion; Solito, Samantha; Pinton, Laura; Valpione, Sara; Bastiat, Guillaume; Mandruzzato, Susanna; Bronte, Vincenzo; Marigo, Ilaria; Benoit, Jean‐Pierre

doi:10.1016/j.biomaterials.2016.04.010

Cited by 129 publications

(85 citation statements)

References 64 publications

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“…[67] To achieve precise and controlled drug delivery, smart nanoparticles with more complex structures and specific drug release properties are also being produced according to the hallmarks of TME, such as weak acidic pH (6.5-6.8), high level of glutathione and hydrogen peroxide (H 2 O 2 ), and disorder of proteinases production, such as matrix metalloproteinase-2 (MMP-2). HDL-mimicking nanodisc Patient-derived neoantigen and cholesterol-modified CpG -- [135] PLGA NP OVA, Pam3Csk4, and Poly(I:C) CD40 on DCs - [136] Chitosan nanoparticle Cell lysate from B16 melanoma Mannose receptor on DCs - [38] Lipo-CpG micelle CpG Albumin hitchhiking - [137] γPGA-based CNNP OVA and poly(I:C) -- [138] PLGA-based AC-NP --- [139] mBiNE CRT HER-2 on tumor cells - [140] T cell activation DMAEMA, PAA, and butyl methacrylate OVA -pH [134] polyPAA OVA -pH [133] CNT MHC1 peptide, anti-CD28, and PLGA NPs encapsulating IL-2 and magnetite -- [141] Magnetic nanocluster MHC1-OVA, anti-CD28, and leukocyte membrane fragments Magnetic navigation - [128] PD-1 receptor-expressing NV --- [142] PEG-PLA NP CTLA-4 siRNA -- [143] Platelet-derived microparticle Anti-PD-L1 Ab -- [144] PEG-PLGA NP Anti-PD-1 Ab and aOX40 -- [145] Super-paramagnetic iron oxide nanoparticle Anti-PD-L1 Ab, anti-CD3/anti-CD28 Ab, fucoidan, and dextran Magnetic navigation - [129] Regulation of TME PLGA NP core with lipid shell Imatinib Nrp1 receptor on Tregs - [43] CDNP consisting of CD and lysine R848 -- [146] NV derived from type 1 macrophage --- [147] Carboxyl-functionalied and aminofunctionalized polystyrene nanoparticle --- [148] Super-paramagnetic iron oxide --- [149] Ferumoxytol --- [150] HDL NP -Scavenger receptor B1 on MDSCs - [151] PEGylated LNC lmGem -- [152] LPH NP HMGA1 siRNA Sigma receptor on tumor cells - [153] LCP NP TGF-β siRNA, tumor antigen, and CpG -- [154] PEG-PLGA NP SD-208 PD-1 on T cells - [155] Nanoparticle assembled from DEAP molecule, PD-L1 antagonist, NGL919, and a substrate peptide of MMP-2 -pH and MMP-2 …”

Section: Doi: 101002/advs201900101mentioning

confidence: 99%

“…[210,211] Treatment with HDL NPs significantly minimized the activity of MDSCs and exerted phenomenal antitumor effect characterized by reduced tumor size and metastasis, and prolonged survival time. [152] A low dose of lmGem-LNC was sufficient to induce remarkable decrease of monocytic MDSCs both in the spleen and tumor. [212] PEGylated lipid nanocapsules (LNCs) containing lauroyl-modified gemcitabine (lmGem) were developed for targeting depletion of monocytic MDSCs.…”

Section: Doi: 101002/advs201900101mentioning

confidence: 99%

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Immunomodulatory Nanosystems

et al. 2019

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Immunotherapy has emerged as an effective strategy for the prevention and treatment of a variety of diseases, including cancer, infectious diseases, inflammatory diseases, and autoimmune diseases. Immunomodulatory nanosystems can readily improve the therapeutic effects and simultaneously overcome many obstacles facing the treatment method, such as inadequate immune stimulation, off‐target side effects, and bioactivity loss of immune agents during circulation. In recent years, researchers have continuously developed nanomaterials with new structures, properties, and functions. This Review provides the most recent advances of nanotechnology for immunostimulation and immunosuppression. In cancer immunotherapy, nanosystems play an essential role in immune cell activation and tumor microenvironment modulation, as well as combination with other antitumor approaches. In infectious diseases, many encouraging outcomes from using nanomaterial vaccines against viral and bacterial infections have been reported. In addition, nanoparticles also potentiate the effects of immunosuppressive immune cells for the treatment of inflammatory and autoimmune diseases. Finally, the challenges and prospects of applying nanotechnology to modulate immunotherapy are discussed.

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Section: Doi: 101002/advs201900101mentioning

confidence: 99%

Section: Doi: 101002/advs201900101mentioning

confidence: 99%

Immunomodulatory Nanosystems

et al. 2019

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“…Higher uptake of lipid nanocapsules was observed in monocytes. Low levels of gemcitabine in the nanocapsules significantly reduced tumor immunosuppression [56]. C57BL/6 CD45.2 mice injected with EG7-OVA tumors were treated with GemC12 lipid nanocapsules on day 8, followed by ACT on day 9.…”

Section: Alternate Targeting Strategiesmentioning

confidence: 99%

Nanoparticle Design Strategies for Effective Cancer Immunotherapy

et al. 2017

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Cancer immunotherapy is a rapidly evolving and paradigm shifting treatment modality that adds a strong tool to the collective cancer treatment arsenal. It can be effective even for late stage diagnoses and has already received clinical approval. Tumors are known to not only avoid immune surveillance but also exploit the immune system to continue local tumor growth and metastasis. Because of this, most immunotherapies, particularly those directed against solid cancers, have thus far only benefited a small minority of patients. Early clinical substantiation lends weight to the claim that cancer immunotherapies, which are adaptive and enduring treatment methods, generate much more sustained and robust anticancer effects when they are effectively formulated in nanoparticles or scaffolds than when they are administered as free drugs. Engineering cancer immunotherapies using nanomaterials is, therefore, a very promising area worthy of further consideration and investigation. This review focuses on the recent advances in cancer immunoengineering using nanoparticles for enhancing the therapeutic efficacy of a diverse range of immunotherapies. The delivery of immunostimulatory agents to antitumor immune cells, such as dendritic or antigen presenting cells, may be a far more efficient tactic to eradicate tumors than delivery of conventional chemotherapeutic and cytotoxic drugs to cancer cells. In addition to its immense therapeutic potential, immunoengineering using nanoparticles also provides a valuable tool for unearthing and understanding the basics of tumor biology. Recent research using nanoparticles for cancer immunotherapy has demonstrated the advantage of physicochemical manipulation in improving the delivery of immunostimulatory agents. In vivo studies have tested a range of particle sizes, mostly less than 300 nm, and particles with both positive and negative zeta potentials for various applications. Material composition and surface modifications have been shown to contribute significantly in selective targeting, efficient delivery and active stimulation of immune system targets. Thus, these investigations, including a wide array of nanoparticles for cancer immunotherapy, substantiate the employment of nanocarriers for efficacious cancer immunotherapies.

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“…After the postsurgical treatment with fibrin gel, tumor recurrence and potential metastatic spread were inhibited ( Figure 5E). [143] Huang and co-workers took one step further to inhibit both the MDSC and T reg cells using nanomedicine carrying plasmid encoding a trap protein of CXC-chemokine ligand 12 (CXCL12), as endogenous CXCL12 expressed by hepatic stellate cells (HSCs) could recruit MDSCs and T reg cells toward the area of inflammation as well as CXCR4 + cancer cells. [142] Aside from TAM, monocytic MDSCs (M-MDSCs) are also immunosuppressive and abundant in the blood and tumor of patients with metastatic melanoma.…”

Section: Nanomedicine For Immunosuppressive Cell Inhibitionmentioning

confidence: 99%

Nanomedicine‐Based Immunotherapy for the Treatment of Cancer Metastasis

et al. 2019

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Metastasis is the leading cause of cancer‐associated death, with poor prognosis even after extensive treatment. The dormancy of metastatic cancer cells during dissemination or after colony formation is one major reason for treatment failure, as most drugs target cells of active proliferation. Immunotherapy has shown great potential in cancer therapy because the activity of effector cells is less affected by the metabolic status of cancer cells. In addition, metastatic cells out of immunosuppressive tumor microenvironment (TME) are more susceptible to immune clearance, although these cells can achieve immune surveillance evasion via strategies such as platelet and macrophage recruitment. Since nanomaterials themselves or their carried drugs have the capability to modulate the immune system, a great amount of focus has been placed on nanomedicine strategies that leverage immune cells participating the metastatic cascade. These nanomedicines successfully inhibit the tumor metastasis and prolong the survival of model animals. Immune cells that are involved in the metastasis cascade are first summarized and then recent and inspiring strategies and nanomaterials in this growing field are highlighted.

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Low dose gemcitabine-loaded lipid nanocapsules target monocytic myeloid-derived suppressor cells and potentiate cancer immunotherapy

Cited by 129 publications

References 64 publications

Immunomodulatory Nanosystems

Immunomodulatory Nanosystems

Nanoparticle Design Strategies for Effective Cancer Immunotherapy

Nanomedicine‐Based Immunotherapy for the Treatment of Cancer Metastasis

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