Antiglioma via regulating oxidative stress and remodeling tumor-associated macrophage using lactoferrin-mediated biomimetic codelivery of simvastatin/fenretinide

Mo, Xiaopeng; Zheng, Zening; He, Yang; Zhong, Huihai; Kang, Xuejia; Shi, Mingjie; Liu, Tuanbing; Jiao, Z.; Huang, Yongzhuo

doi:10.1016/j.jconrel.2018.08.012

Cited by 55 publications

(58 citation statements)

References 31 publications

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“…Activated ERK signal promoted cell survival under ROS microenvironment 19 and inactivated ERK pathway induced the ROS-mediated mitochondrial apoptotic pathway. 20 Similarly, AKT activation maintained the cell redox homeostasis, while AKT suppression weakened the antioxidant capacity of cells. 21 Both proteins and extracellular vesicles, especially exosomes, have been reported to mediate pivotal paracrine functions of MSCs.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells alleviate hypoxia-induced oxidative stress and enhance the pro-survival pathways in porcine islets

Tan

Nie

Chen

et al. 2019

Exp Biol Med (Maywood)

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Islet transplantation is a promising treatment for selected patients with type 1 diabetes mellitus (T1DM). Hypoxia and oxidative stress are major causes of damage to transplanted islets. Mesenchymal stem cells (MSCs) have been shown to enhance cell survival mainly through paracrine secretion. However, mechanisms of action underlying the protective effects of MSCs on islets have not been fully elucidated. In this study, we investigated whether human umbilical cord-derived MSCs (huc-MSCs) could inhibit hypoxia and ROS-related cell death of neonatal porcine islet cell clusters (NICCs) and further determined the underlying molecular mechanisms. NICCs were cultured in vitro under normoxic and hypoxic (1% O2) conditions with or without MSC-conditioned medium (MSC-CM). Apoptosis of NICCs was evaluated by the AO/EB staining and Annexin V/PI flow cytometry analysis. Total and mitochondrial ROS production was detected by fluorometric assays. Western blot and the ERK pathway inhibitor, PD98059, were used to assess the possible pathways involved. The results showed that MSC-CM suppressed hypoxia-induced oxidative stress and cell death of NICCs. MSC-CM also activated several pro-survival pathways in NICCs under hypoxic conditions. Furthermore, MSC-secreted exosomes and IL-6 partially recapitulated the multifunctional benefits of MSC-CM. This study showed that huc-MSCs protected NICCs from hypoxia-induced cell death by regulating the cell redox state and cell signaling pathways. This increased understanding may enable MSCs to become a more promising adjuvant cell therapy for islet transplantation. Impact statement The utilization of mesenchymal stem cells (MSCs) is a promising approach to serve as adjuvant therapy for islet transplantation. But the inability to translate promising preclinical results into sound therapeutic effects in human subjects indicates a lack of key knowledge of MSC-islet interactions that warrant further research. Hypoxia and oxidative stress are critical factors which lead to a tremendous loss of islet grafts. However, previous studies mainly focused on other aspects of MSC protection such as inducing revascularization, enhancing insulin secretion, and reducing islet apoptosis. In this study, we aim to investigate whether MSC can protect islet cells from hypoxic damage by inhibiting ROS production and the potential underlying pathways involved. We also explore the effects of MSC-derived exosomes and IL-6 on hypoxia-injured islets. Our data provide new molecular targets for developing MSC applications, and this may ultimately promote the efficiency of clinical islet transplantation.

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Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells alleviate hypoxia-induced oxidative stress and enhance the pro-survival pathways in porcine islets

Tan

Nie

Chen

et al. 2019

Exp Biol Med (Maywood)

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“…Importantly, Lf was found efficient in the specific targeting of central nervous system (CNS) by overcoming blood-brain barrier (BBB) [206][207][208][209]. As a matter of fact, one of the most critical limitation for the treatment of CNS pathologies, including cancer, is represented by BBB which restricts the delivery of therapeutic agents to the brain.…”

Section: Lactoferrin As a Cargo For Cancer Targetingmentioning

confidence: 99%

“…The use of Lf as carrier for CNS treatment is due to the high expression of LRP1 on cells constituting BBB and even more on glioma cells, the most recurrent type of cancer in the brain [66,210]. Overall, studies employing Lf-bearing NPs co-loaded with different type of chemotherapeutics in the treatment of glioblastoma reported a good safety profile, an enhanced permeation of BBB and efficient drug delivery to glioma cells [206][207][208][209].…”

Section: Lactoferrin As a Cargo For Cancer Targetingmentioning

confidence: 99%

Lactoferrin’s Anti-Cancer Properties: Safety, Selectivity, and Wide Range of Action

et al. 2020

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Despite recent advances in cancer therapy, current treatments, including radiotherapy, chemotherapy, and immunotherapy, although beneficial, present attendant side effects and long-term sequelae, usually more or less affecting quality of life of the patients. Indeed, except for most of the immunotherapeutic agents, the complete lack of selectivity between normal and cancer cells for radioand chemotherapy can make them potential antagonists of the host anti-cancer self-defense over time. Recently, the use of nutraceuticals as natural compounds corroborating anti-cancer standard therapy is emerging as a promising tool for their relative abundance, bioavailability, safety, low-cost effectiveness, and immuno-compatibility with the host. In this review, we outlined the anti-cancer properties of Lactoferrin (Lf), an iron-binding glycoprotein of the innate immune defense. Lf shows high bioavailability after oral administration, high selectivity toward cancer cells, and a wide range of molecular targets controlling tumor proliferation, survival, migration, invasion, and metastasization. Of note, Lf is able to promote or inhibit cell proliferation and migration depending on whether it acts upon normal or cancerous cells, respectively. Importantly, Lf administration is highly tolerated and does not present significant adverse effects. Moreover, Lf can prevent development or inhibit cancer growth by boosting adaptive immune response. Finally, Lf was recently found to be an ideal carrier for chemotherapeutics, even for the treatment of brain tumors due to its ability to cross the blood-brain barrier, thus globally appearing as a promising tool for cancer prevention and treatment, especially in combination therapies.

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“…Accordingly, they encapsulated simvastatin and fenretinide into a lactoferrin nanoparticle system to repolarize TAMs from M2 phenotype to M1 and induce the innate immunity for anti‐glioma therapy. [ 53 ] Likewise, hydrazinocurcumin, a synthesized substitute of curcumin with STAT3 inhibitory effect, hold great potential for macrophages repolarization toward M1 phenotype. A legumain‐sensitive liposome loading hydrazinocurcumin was developed to reprogram TAMs to antitumoral M1 macrophages by STAT3 suppression and exert the antitumor effects in a breast cancer model.…”

Section: Nanomedicine Mediated Tams Targeting To Promote Their Re‐edumentioning

confidence: 99%

Reprogramming Tumor Associated Macrophages toward M1 Phenotypes with Nanomedicine for Anticancer Immunotherapy

Gong

et al. 2020

Advanced Therapeutics

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Tumor-associated macrophages (TAMs), one of the most important constituents in tumor immunosuppressive microenvironments, are a potential therapeutic target due to their essential role in promoting tumor progression and metastasis. Macrophages are usually divided into two categories of protumoral M2-like TAMs and antitumoral M1 phenotypes at the two extremes. Reprogramming M2-like TAMs toward tumoricidal M1 phenotype is especially intriguing in terms of the restoration of antitumor immunity for anticancer immunotherapy. In this review, the recent advances of nanomedicine-mediated reprogramming of TAMs from M2 to M1 to elicit the antitumor immunity are discussed. This reprogramming can be achieved via direct re-education by targeted delivery of various active agents to TAMs and indirect re-education by modulating the abnormal tumor microenvironment. Perspectives on nanomedicine mediated TAMs-M1 reprogramming for effective anticancer immunotherapy are also presented.

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Antiglioma via regulating oxidative stress and remodeling tumor-associated macrophage using lactoferrin-mediated biomimetic codelivery of simvastatin/fenretinide

Cited by 55 publications

References 31 publications

Mesenchymal stem cells alleviate hypoxia-induced oxidative stress and enhance the pro-survival pathways in porcine islets

Mesenchymal stem cells alleviate hypoxia-induced oxidative stress and enhance the pro-survival pathways in porcine islets

Lactoferrin’s Anti-Cancer Properties: Safety, Selectivity, and Wide Range of Action

Reprogramming Tumor Associated Macrophages toward M1 Phenotypes with Nanomedicine for Anticancer Immunotherapy

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