A Novel DNA Aptamer for Dual Targeting of Polymorphonuclear Myeloid-derived Suppressor Cells and Tumor Cells

Liu, Haoran; Mai, Junhua; Shen, Jianliang; Wolfram, Joy; Li, Zhaoqi; Zhang, Guodong; Xu, Rong; Li, Yan; Mu, Chaofeng; Zu, Youli; Li, Xin; Lokesh, G.L.; Thiviyanathan, Varatharasa; Volk, David E.; Gorenstein, David G.; Ferrari, Mauro; Hu, Zhongbo; Shen, Haifa

doi:10.7150/thno.21342

Cited by 50 publications

(41 citation statements)

References 48 publications

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“…Methods have also been developed for in vivo SELEX, where aptamers are selected by binding tumors in situ in animal models . This has resulted in aptamers with minimal off‐target binding to healthy tissues that can bind multiple cell types in heterogeneous tumors . Because aptamers can be generated for a range of molecules expressed in tumors, this targeting approach circumvents the problem of resistance, which is common when targeting a single receptor …”

Section: Tumor Targetingmentioning

confidence: 99%

Cancer‐Targeting Nanoparticles for Combinatorial Nucleic Acid Delivery

2019

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Nucleic acids are a promising type of therapeutic for the treatment of a wide range of conditions, including cancer, but they also pose many delivery challenges. For efficient and safe delivery to cancer cells, nucleic acids must generally be packaged into a vehicle, such as a nanoparticle, that will allow them to be taken up by the target cells and then released in the appropriate cellular compartment to function. As with other types of therapeutics, delivery vehicles for nucleic acids must also be designed to avoid unwanted side effects; thus, the ability of such carriers to target their cargo to cancer cells is crucial. Classes of nucleic acids, hurdles that must be overcome for effective intracellular delivery, types of nonviral nanomaterials used as delivery vehicles, and the different strategies that can be employed to target nucleic acid delivery specifically to tumor cells are discussed. Additonally, nanoparticle designs that facilitate multiplexed delivery of combinations of nucleic acids are reviewed.

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Section: Tumor Targetingmentioning

confidence: 99%

Cancer‐Targeting Nanoparticles for Combinatorial Nucleic Acid Delivery

2019

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“…As a single‐stranded oligonucleotide, aptamers (Apts) have emerged as a promising targeting agent for specific penetration into biological compartments with non‐immunogenicity 17. AS1411 Apt is one of the DNA Apts which can bind to nucleolin (NCL) with high specificity and affinity 18.…”

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confidence: 99%

Polydopamine‐Modified Black Phosphorous Nanocapsule with Enhanced Stability and Photothermal Performance for Tumor Multimodal Treatments

et al. 2018

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As a novel 2D material, black phosphorus (BP) nanosheets are considered as a promising candidate for drug delivery platform for synergistic chemo/photothermal therapy. However, the intrinsic instability of bare BP poses a challenge in its biomedical applications. To date, some strategies have been employed to prevent BP from rapid ambient degradation. Unfortunately, most of these strategies are not suitable for the drug delivery systems. Here, a simple polydopamine modification method is developed to enhance the stability and photothermal performance of bare BP nanosheets. Then, this nanocapsule is used as a multifunctional codelivery system for the targeted chemo, gene, and photothermal therapy against multidrug‐resistant cancer. The enhanced tumor therapy effect is demonstrated by both in vitro and in vivo studies.

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“…Aptamer (T1) conjugated to liposomal doxorubicin [32] or lipid-coated biodegradable hollow mesoporous silica nanoparticle co-encapsulated with all-trans retinoic acid (ATRA), doxorubicin and IL-2 [33] showed a high affinity for both tumor cells and PMN-MDSCs [32] or to induce a reduction in the number of MDSCs in the tumor microenvironment of mouse models [33]. However, these systems showed no affinity for M-MDSCs or macrophages therefore reducing their applicability only to tumors in which PMN MDSCs are mainly involved [32]. Besides, they affected other cell subsets present in the tumor microenvironment, and thus cannot be considered a nanosystem with a specific targeting towards MDSCs.…”

Section: Discussionmentioning

confidence: 99%

Targeting of immunosuppressive myeloid cells from glioblastoma patients by modulation of size and surface charge of lipid nanocapsules

et al. 2020

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Background: Myeloid derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) are two of the major players involved in the inhibition of anti-tumor immune response in cancer patients, leading to poor prognosis. Selective targeting of myeloid cells has therefore become an attractive therapeutic strategy to relieve immunosuppression and, in this frame, we previously demonstrated that lipid nanocapsules (LNCs) loaded with lauroyl-modified gemcitabine efficiently target monocytic MDSCs in melanoma patients. In this study, we investigated the impact of the physico-chemical characteristics of LNCs, namely size and surface potential, towards immunosuppressive cell targeting. We exploited myeloid cells isolated from glioblastoma patients, which play a relevant role in the immunosuppression, to demonstrate that tailored nanosystems can target not only tumor cells but also tumor-promoting cells, thus constituting an efficient system that could be used to inhibit their function. Results: The incorporation of different LNC formulations with a size of 100 nm, carrying overall positive, neutral or negative charge, was evaluated on leukocytes and tumor-infiltrating cells freshly isolated from glioblastoma patients. We observed that the maximum LNC uptake was obtained in monocytes with neutral 100 nm LNCs, while positively charged 100 nm LNCs were more effective on macrophages and tumor cells, maintaining at low level the incorporation by T cells. The mechanism of uptake was elucidated, demonstrating that LNCs are incorporated mainly by caveolae-mediated endocytosis. Conclusions: We demonstrated that LNCs can be directed towards immunosuppressive cells by simply modulating their size and charge thus providing a novel approach to exploit nanosystems for anticancer treatment in the frame of immunotherapy.

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A Novel DNA Aptamer for Dual Targeting of Polymorphonuclear Myeloid-derived Suppressor Cells and Tumor Cells

Cited by 50 publications

References 48 publications

Cancer‐Targeting Nanoparticles for Combinatorial Nucleic Acid Delivery

Cancer‐Targeting Nanoparticles for Combinatorial Nucleic Acid Delivery

Polydopamine‐Modified Black Phosphorous Nanocapsule with Enhanced Stability and Photothermal Performance for Tumor Multimodal Treatments

Targeting of immunosuppressive myeloid cells from glioblastoma patients by modulation of size and surface charge of lipid nanocapsules

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