Biodegradable Nanoplatforms with the Multiple Modulation of Tumor Microenvironment for Enhanced Sonodynamic Therapy
TL;DR: Based on the multiple adjustments to tumor microenvironment, the nanoplatform displayed extraordinary sonodynamic therapeutic effect with low systemic toxicity.
Abstract: The specific microenvironment of solid tumors, which is characterized by hypoxia, overexpression of glutathione (GSH) and high accumulation of anti-inflammatory tumor associated macrophages (TAMs), limits the efficiency of sonodynamic therapy (SDT). Herein, a multifunctional nanoplatform was engineered to modulate the tumor microenvironment for highly efficient SDT. In this system, sonosensitizers and catalase were encapsulated in disulfide-bridged mesoporous organosilicon nanoparticles with high loading, which protected the activity of catalase and ensure the stability of sonosensitizers and enzyme. Subsequently hyaluronic acid was grafted onto the nanoplatform to reeducate TAMs and induce the secretion of exogenous hydrogen peroxide. Due to the good protection of enzyme, the catalase within the nanoplatform efficiently produced the mount of O 2 through decomposing the H 2 O 2 in tumor tissues, which remarkably alleviated tumor hypoxia. Furthermore, degradation of the nanoparticles was observed in response to GSH, which effectively decreased the intracellular GSH level, further favoring SDT-triggered anticancer effect. Based on the multiple adjustments to tumor microenvironment, our nanoplatform displayed extraordinary sonodynamic therapeutic effect with low systemic toxicity.
References
More filters
TL;DR: The catalase assay performed using polarographic and spectrophotometric determination of hydrogen peroxide yielded a good correlation and in 742 healthy individuals the mean and SD values of serumCatalase were 50.5 +/- 18.1 kU/l with 17.7% higher activity in males than in females.
1,780 citations
TL;DR: The microenvironment of solid tumors is characterized by a reactive stroma with an abundance of inflammatory mediators and leukocytes, dysregulated vessels and proteolytic enzymes, which makes TAM an attractive target of novel biological therapies of tumors.
Abstract: The microenvironment of solid tumors is characterized by a reactive stroma with an abundance of inflammatory mediators and leukocytes, dysregulated vessels and proteolytic enzymes TAM, major players in the connection between inflammation and cancer, summarize a number of functions (eg, promotion of tumor cell proliferation and angiogenesis, incessant matrix turnover, repression of adaptive immunity), which ultimately have an important impact on disease progression Thus, together with other myeloid-related cells present at the tumor site (Tie2 macrophages and MDSCs), TAM represent an attractive target of novel biological therapies of tumors
1,225 citations
"Biodegradable Nanoplatforms with th..." refers background in this paper
...enriched by macrophages, which is termed tumor-associated macrophages (TAMs)[21, 22]....
[...]
...[22] Solinas G, Germano G, Mantovani A, Allavena P....
[...]
TL;DR: An overview of mechanisms responsible for TAM recruitment is presented and the roles of TAMs in the regulation of tumor angiogenesis, invasion, metastasis, immunosuppression, and chemotherapeutic resistance are highlighted.
Abstract: During tumor progression, circulating monocytes and macrophages are actively recruited into tumors where they alter the tumor microenvironment to accelerate tumor progression. Macrophages shift their functional phenotypes in response to various microenvironmental signals generated from tumor and stromal cells. Based on their function, macrophages are divided broadly into two categories: classical M1 and alternative M2 macrophages. The M1 macrophage is involved in the inflammatory response, pathogen clearance, and antitumor immunity. In contrast, the M2 macrophage influences an anti-inflammatory response, wound healing, and pro-tumorigenic properties. Tumor-associated macrophages (TAMs) closely resemble the M2-polarized macrophages and are critical modulators of the tumor microenvironment. Clinicopathological studies have suggested that TAM accumulation in tumors correlates with a poor clinical outcome. Consistent with that evidence, experimental and animal studies have supported the notion that TAMs can provide a favorable microenvironment to promote tumor development and progression. In this review article, we present an overview of mechanisms responsible for TAM recruitment and highlight the roles of TAMs in the regulation of tumor angiogenesis, invasion, metastasis, immunosuppression, and chemotherapeutic resistance. Finally, we discuss TAM-targeting therapy as a promising novel strategy for an indirect cancer therapy.
1,161 citations
"Biodegradable Nanoplatforms with th..." refers background in this paper
...enriched by macrophages, which is termed tumor-associated macrophages (TAMs)[21, 22]....
[...]
...[21] Chanmee T, Ontong P, Konno K, Itano N....
[...]
TL;DR: The results suggest that ferumoxytol could be applied 'off label' to protect the liver from metastatic seeds and potentiate macrophage-modulating cancer immunotherapies.
Abstract: Until now, the Food and Drug Administration (FDA)-approved iron supplement ferumoxytol and other iron oxide nanoparticles have been used for treating iron deficiency, as contrast agents for magnetic resonance imaging and as drug carriers. Here, we show an intrinsic therapeutic effect of ferumoxytol on the growth of early mammary cancers, and lung cancer metastases in liver and lungs. In vitro, adenocarcinoma cells co-incubated with ferumoxytol and macrophages showed increased caspase-3 activity. Macrophages exposed to ferumoxytol displayed increased mRNA associated with pro-inflammatory Th1-type responses. In vivo, ferumoxytol significantly inhibited growth of subcutaneous adenocarcinomas in mice. In addition, intravenous ferumoxytol treatment before intravenous tumour cell challenge prevented development of liver metastasis. Fluorescence-activated cell sorting (FACS) and histopathology studies showed that the observed tumour growth inhibition was accompanied by increased presence of pro-inflammatory M1 macrophages in the tumour tissues. Our results suggest that ferumoxytol could be applied 'off label' to protect the liver from metastatic seeds and potentiate macrophage-modulating cancer immunotherapies.
1,089 citations
"Biodegradable Nanoplatforms with th..." refers background in this paper
...[20] Zanganeh S, Hutter G, Spitler R, Lenkov O, Mahmoudi M, Shaw AK, et al....
[...]
...superoxide anion radicals and nitric oxide to exert their antiproliferative and cytotoxic activities[19, 20]....
[...]
TL;DR: Macrophages are widely distributed innate immune cells that play indispensable roles in the innate and adaptive immune response to pathogens and in-tissue homeostasis and mediating macrophage to resist tumors is considered to be potential therapy.
Abstract: Macrophages are widely distributed innate immune cells that play indispensable roles in the innate and adaptive immune response to pathogens and in-tissue homeostasis. Macrophages can be activated by a variety of stimuli and polarized to functionally different phenotypes. Two distinct subsets of macrophages have been proposed, including classically activated (M1) and alternatively activated (M2) macrophages. M1 macrophages express a series of proinflammatory cytokines, chemokines, and effector molecules, such as IL-12, IL-23, TNF-α, iNOS and MHCI/II. In contrast, M2 macrophages express a wide array of anti-inflammatory molecules, such as IL-10, TGF-β, and arginase1. In most tumors, the infiltrated macrophages are considered to be of the M2 phenotype, which provides an immunosuppressive microenvironment for tumor growth. Furthermore, tumor-associated macrophages secrete many cytokines, chemokines, and proteases, which promote tumor angiogenesis, growth, metastasis, and immunosuppression. Recently, it was also found that tumor-associated macrophages interact with cancer stem cells. This interaction leads to tumorigenesis, metastasis, and drug resistance. So mediating macrophage to resist tumors is considered to be potential therapy.
787 citations
"Biodegradable Nanoplatforms with th..." refers background in this paper
...[19] Hao N, Lu M, Fan Y, Cao Y, Zhang Z, Yang S....
[...]
...superoxide anion radicals and nitric oxide to exert their antiproliferative and cytotoxic activities[19, 20]....
[...]