Sequential depletion of myeloid-derived suppressor cells and tumor cells with a dual-pH-sensitive conjugated micelle system for cancer chemoimmunotherapy

Wan, Dandan; Yang, Yiliang; Liu, Yiyao; Cun, Xingli; Li, Man; Xu, Shanshan; Zhao, Wei; Xiang, Yangyang; Qiu, Yue; Yu, Qianwen; Tang, Xian; Zhang, Zhirong; He, Qin

doi:10.1016/j.jconrel.2019.11.011

Cited by 34 publications

(18 citation statements)

References 46 publications

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“…Such effects of immune enhancement and stimulation conferred by sunitinib were consistent with the observations in the literature. [14,21] The combination of these two drugs (DS@ HLipo+L) exhibited the strongest enhancement in antitumor immunity. However, without light irradiation (DS@HLipo), the benefits were largely compromised, highlighting the advantage and necessity of light-triggered rapid release of sunitinib and liberation of DOX-NP in stimulating the immune system.…”

Section: Anticancer Therapy In Vivomentioning

confidence: 99%

Light‐Triggered Efficient Sequential Drug Delivery of Biomimetic Nanosystem for Multimodal Chemo‐, Antiangiogenic, and Anti‐MDSC Therapy in Melanoma

Lai

Pan

et al. 2022

Advanced Materials

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In view of the multiple pathological hallmarks of tumors, nanosystems for the sequential delivery of various drugs whose targets are separately located inside and outside tumor cells are desired for improved cancer therapy. However, current sequential delivery is mainly achieved through enzyme‐ or acid‐dependent degradation of the nanocarrier, which would be influenced by the heterogeneous tumor microenvironment, and unloading efficiency of the drug acting on the target outside tumor cells is usually unsatisfactory. Here, a light‐triggered sequential delivery strategy based on a liposomal formulation of doxorubicin (DOX)‐loaded small‐sized polymeric nanoparticles (DOX‐NP) and free sunitinib in the aqueous cavity, is developed. The liposomal membrane is doped with photosensitizer porphyrin–phospholipid (PoP) and hybridized with red blood cell membrane to confer biomimetic features. Near‐infrared light‐induced membrane permeabilization triggers the “ultrafast” and “thorough” release of sunitinib (100% release in 5 min) for antiangiogenic therapy and also myeloid‐derived suppressor cell (MDSC) inhibition to reverse the immunosuppressive tumor environment. Subsequently, the small‐sized DOX‐NP liberated from the liposomes is more easily uptaken by tumor cells for improved immunogenic chemotherapy. RNA sequencing and immune‐related assay indicates therapeutic immune enhancement. This light‐triggered sequential delivery strategy demonstrates the potency in cancer multimodal therapy against multiple targets in different spatial positions in tumor microenvironment.

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Section: Anticancer Therapy In Vivomentioning

confidence: 99%

Light‐Triggered Efficient Sequential Drug Delivery of Biomimetic Nanosystem for Multimodal Chemo‐, Antiangiogenic, and Anti‐MDSC Therapy in Melanoma

Lai

Pan

et al. 2022

Advanced Materials

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“…Notably, modifications of the nanoparticle surface charge dictate the subset of immune cells that will be targeted, where neutral particles are primarily engulfed by monocytes and M-MDSCs and negative particles are predominantly captured by macrophages in tumour samples of patients with glioma [248]. Alternatively, dual-pH-sensitive vesicles have been designed and tested to directly transport immunomodulatory drugs into the TME [249]. These premises establish a solid basis for CRISPR-loaded nanoparticle-mediated approaches to relieve MDSC-derived immunosuppression, and these could soon be translated into new cancer immunotherapies.…”

Section: New Perspectives In Mdsc-targeting Approachesmentioning

confidence: 99%

A Complex Metabolic Network Confers Immunosuppressive Functions to Myeloid-Derived Suppressor Cells (MDSCs) within the Tumour Microenvironment

Hofer

Sario

Musiu

et al. 2021

Cells

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Myeloid-derived suppressor cells (MDSCs) constitute a plastic and heterogeneous cell population among immune cells within the tumour microenvironment (TME) that support cancer progression and resistance to therapy. During tumour progression, cancer cells modify their metabolism to sustain an increased energy demand to cope with uncontrolled cell proliferation and differentiation. This metabolic reprogramming of cancer establishes competition for nutrients between tumour cells and leukocytes and most importantly, among tumour-infiltrating immune cells. Thus, MDSCs that have emerged as one of the most decisive immune regulators of TME exhibit an increase in glycolysis and fatty acid metabolism and also an upregulation of enzymes that catabolise essential metabolites. This complex metabolic network is not only crucial for MDSC survival and accumulation in the TME but also for enhancing immunosuppressive functions toward immune effectors. In this review, we discuss recent progress in the field of MDSC-associated metabolic pathways that could facilitate therapeutic targeting of these cells during cancer progression.

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“…The depletion of these immune cells induced a major infiltration of cytotoxic T cells (CD8+) in the tumoral tissue. Wan et al have recently developed pH-sensitive size-changeable micelles capable of delivering liver-X nuclear receptor (LXR) agonist RGX-104 and paclitaxel (PTX) to tumor stromal cells and tumor cells, respectively, which are two cell populations located in different areas of the tumor [56]. This system was composed of two types of micelles, which released their payloads under different pH conditions.…”

Section: Nanoparticles To Enhance the Antitumoral Action Of Innate Immentioning

confidence: 99%

Tumor Targeted Nanocarriers for Immunotherapy

Baeza

2020

Molecules

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The paramount discovery of passive accumulation of nanoparticles in tumoral tissues triggered the development of a wide number of different nanoparticles capable of transporting therapeutic agents to tumoral tissues in a controlled and selective way. These nanocarriers have been endowed with important capacities such as stimuli-responsive properties, targeting abilities, or the capacity to be monitored by imaging techniques. However, after decades of intense research efforts, only a few nanomedicines have reached the market. The reasons for this disappointing outcome are varied, from the high tumor-type dependence of enhanced permeation and retention (EPR) effect to the poor penetration capacity of nanocarriers within the cancerous tissue, among others. The rapid nanoparticle clearance by immune cells, considered another important barrier, which compromises the efficacy of nanomedicines, would become an important ally in the fight against cancer. In the last years, the fine-tuned ability of immune cells to recognize and engulf nanoparticles have been exploited to deliver immunoregulating agents to specific immune cell populations selectively. In this work, the recent advances carried out in the development of nanocarriers capable of operating with immune and tumoral cells in order to orchestrate an efficient antitumoral response will be presented. The combination of nanoparticles and immunotherapy would deliver powerful weapons to the clinicians that offer safer and more efficient antitumoral treatments for the patients.

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Sequential depletion of myeloid-derived suppressor cells and tumor cells with a dual-pH-sensitive conjugated micelle system for cancer chemoimmunotherapy

Cited by 34 publications

References 46 publications

Light‐Triggered Efficient Sequential Drug Delivery of Biomimetic Nanosystem for Multimodal Chemo‐, Antiangiogenic, and Anti‐MDSC Therapy in Melanoma

Light‐Triggered Efficient Sequential Drug Delivery of Biomimetic Nanosystem for Multimodal Chemo‐, Antiangiogenic, and Anti‐MDSC Therapy in Melanoma

A Complex Metabolic Network Confers Immunosuppressive Functions to Myeloid-Derived Suppressor Cells (MDSCs) within the Tumour Microenvironment

Tumor Targeted Nanocarriers for Immunotherapy

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