CD44 targeting nanodrug based on chondroitin sulfate for melanoma therapy by inducing mitochondrial apoptosis pathways

Li, Yan; Hou, Huiwen; Zengmei, Liu; Wen, Ting‐Chi; Wang, Jie; Lu, Lu; Fu, Jiaai; Gao, Didi; Zhao, Fei; Gao, Xueshan; Ling, Peixue; Wang, Fengshan; Sun, Feng; Tan, Haining

doi:10.1016/j.carbpol.2023.121255

Cited by 7 publications

(4 citation statements)

References 40 publications

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“… 126 Moreover, nanodrug based on CS could target CD44 to treat melanoma by inducing mitochondrial apoptosis. 127 …”

Section: Cd44 In Neoplastic Diseasesmentioning

confidence: 99%

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CD44 and its implication in neoplastic diseases

Xu,

Bai,

Lan

et al. 2024

MedComm

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CD44, a nonkinase single span transmembrane glycoprotein, is a major cell surface receptor for many other extracellular matrix components as well as classic markers of cancer stem cells and immune cells. Through alternative splicing of CD44 gene, CD44 is divided into two isoforms, the standard isoform of CD44 (CD44s) and the variant isoform of CD44 (CD44v). Different isoforms of CD44 participate in regulating various signaling pathways, modulating cancer proliferation, invasion, metastasis, and drug resistance, with its aberrant expression and dysregulation contributing to tumor initiation and progression. However, CD44s and CD44v play overlapping or contradictory roles in tumor initiation and progression, which is not fully understood. Herein, we discuss the present understanding of the functional and structural roles of CD44 in the pathogenic mechanism of multiple cancers. The regulation functions of CD44 in cancers‐associated signaling pathways is summarized. Moreover, we provide an overview of the anticancer therapeutic strategies that targeting CD44 and preclinical and clinical trials evaluating the pharmacokinetics, efficacy, and drug‐related toxicity about CD44‐targeted therapies. This review provides up‐to‐date information about the roles of CD44 in neoplastic diseases, which may open new perspectives in the field of cancer treatment through targeting CD44.

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“… 126 Moreover, nanodrug based on CS could target CD44 to treat melanoma by inducing mitochondrial apoptosis. 127 …”

Section: Cd44 In Neoplastic Diseasesmentioning

confidence: 99%

“…For instance, expressing BMP4/7‐dependent Id1/3 protein was reported to decrease the survival rate in melanoma patients promoted by HA–CD44 interactions with BMPR 126 . Moreover, nanodrug based on CS could target CD44 to treat melanoma by inducing mitochondrial apoptosis 127 …”

Section: Cd44 In Neoplastic Diseasesmentioning

confidence: 99%

CD44 and its implication in neoplastic diseases

Xu,

Bai,

Lan

et al. 2024

MedComm

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“…CD44, a cell surface receptor highly expressed on CRC cells, became our focus due to its potential signi cance. CS, known to speci cally target the CD44 receptor, was selected as the modifying agent to facilitate the binding of CS-HAP NPs to CRC cells by recognizing this receptor on the tumor cell membrane [32]. In our study, CRC cells were incubated with CS-HAP@ATO NPs for 8 h, and observations were made using TEM.…”

Section: In Vitro Cellular Uptake and Anti-tumor Effects Of Cs-hap@at...mentioning

confidence: 99%

“…For instance, some tumor cells exhibit a signi cant presence of CD44v receptors on their cell membranes. The CD44v receptor, a variant of the CD44 receptor, serves as a speci c binding site for hyaluronic acid and enables cells to speci cally recognize and interact with glycosaminoglycan-based biomaterials like CS [32,33]. Furthermore, atorvastatin (ATO), usually an enzyme inhibitor, wields negative effects on the mevalonate pathway by competitively inhibiting HMG-CoA reductase activity and curtails the production of cellular ubiquinone (CoQ10) [34].…”

Section: Introductionmentioning

confidence: 99%

Tumor-targeting hydroxyapatite nanoparticles for remodeling tumor immune microenvironment (TIME) by activating mitoDNA- pyroptosis pathway in cancer

Yang,

Zhu

et al. 2023

Preprint

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In recent years, immunotherapy has emerged as a promising strategy for treating solid tumors, although its efficacy remains limited to a subset of patients. Transforming non-responsive "cold" tumor types into immuno-responsive "hot" ones is critical to enhance the efficacy of immune-based cancer treatments. Pyroptosis, a programmed cell death mechanism, not only effectively eliminates tumor cells but also triggers a potent inflammatory response to initiate anti-tumor immune activities. This sheds light on the potential of pyroptosis to sensitize tumors to immune therapy. Hence, it is urgent to explore and develop novel treatments (e.g., nanomedicines) which are capable of inducing pyroptosis. In this study, we constructed tumor-targeting nanoparticles (CS-HAP@ATO NPs) by loading atorvastatin (ATO) onto chondroitin sulfate (CS) modified hydroxyapatite (HAP) nanoparticles (CS-HAP). CS was strategically employed to target tumor cells, while HAP exhibited the capacity to release calcium ions (Ca2+) in response to the tumor microenvironment. Moreover, ATO disrupted the mitochondrial function was disrupted, leading to intracellular energy depletion and consequential changes in mitochondrial membrane permeability, following by the influx of Ca2+ into the cytoplasm and mitochondria. CS and HAP synergetically augmented mitochondrial calcium overload, inciting the production of substantial amount of reactive oxygen species (ROS) and the subsequent liberation of mitochondrial DNA (mitoDNA). This intricate activation process promoted the assembly of inflammasomes, most notably the NLRP3 inflammasome, followed by triggering caspase-1 activation. The activated caspase-1 was able to induce gasderminD (GSDMD) protein cleavage and present the GSDM-N domain, which interacted with membrane phospholipids on the cell membrane. Then, the cell membrane permeability was raised, cellular swelling was observed, and abundant cell contents and inflammatory mediators were released. Ultimately, this orchestrated sequence of events served to enhance the anti-tumor immunoresponse within the organism.

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