pH-responsive Sulfated Hyaluronic Acid Nanoparticles Targeting Tumor Cells and CAFs for the Treatment of Breast Cancer

Wang, Di; Wu, Jingliang; Qi, Cuiping; Dong, Jinping; Ding, Xueying; Yang, Guohua; Liu, Shuzhen; Zhang, Bo; Gao, Zhiqin; Wei, Xiuhong; Liu, Hongying

doi:10.2174/1574892817666220510123820

Cited by 6 publications

(3 citation statements)

References 47 publications

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“…Second, the chemotherapeutic drug SK was loaded into HFM by electrostatic adsorption to obtain HFM@SK. Since previous studies have shown that HA could target tumor cells, the HA modification can make the nanomaterials gather more in the tumor site. − Finally, HA was modified on the surface of HFM@SK to improve the tumor-targeting effect.…”

Section: Resultsmentioning

confidence: 99%

Shikonin-Loaded Hollow Fe-MOF Nanoparticles for Enhanced Microwave Thermal Therapy

Chen,

Zhao,

Ren

et al. 2023

ACS Biomater. Sci. Eng.

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Microwave (MW) thermal therapy has been widely used for the treatment of cancer in clinics, but it still shows limited efficacy and a high recurrence rate owing to non-selective heat delivery and thermo-resistance. Regulating glycolysis shows great promise to improve MW thermal therapy since glycolysis plays an important role in thermoresistance, progression, metabolism, and recurrence. Herein, we developed a delivery nanosystem of shikonin (SK)-loaded and hyaluronic acid (HA)-modified hollow Fe-MOF (HFM), HFM@SK@ HA, as an efficient glycolysis-meditated agent to improve the efficacy of MW thermal therapy. The HFM@SK@HA nanosystem shows a high SK loading capacity of 31.7 wt %. The loaded SK can be effectively released from the HFM@SK@HA under the stimulation of an acidic tumor microenvironment and MW irradiation, overcoming the intrinsically low solubility and severe toxicity of SK. We also find that the HFM@SK@HA can not only greatly improve the heating effect of MW in the tumor site but also mediate MW-enhancing dynamic therapy efficiency by catalyzing the endogenous H 2 O 2 to generate reactive oxygen species (ROS). As such, the MW irradiation treatment in the presence of HFM@SK@HA in vitro enables a highly improved anti-tumor efficacy due to the combined effect of released SK and generated ROS on inhibiting glycolysis in cancer cells. Our in vivo experiments show that the tumor inhibition rate is up to 94.75% ± 3.63% with no obvious recurrence during the 2 weeks after treatment. This work provides a new strategy for improving the efficacy of MW thermal therapy.

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Section: Resultsmentioning

confidence: 99%

Shikonin-Loaded Hollow Fe-MOF Nanoparticles for Enhanced Microwave Thermal Therapy

Chen,

Zhao,

Ren

et al. 2023

ACS Biomater. Sci. Eng.

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“…HA upon absorbing water swells up to 1000 times its dry volume, forming a hydrated and loose network that helps make pH‐sensitive hydrogels 2 . HA can be made to crosslink with divinyl sulfone (DVS) in saline media, where the vinyl groups of DVS and hydroxyl groups of HA make covalent linkages 62 . These crosslinked matrices have exceptional mucoadhesive characteristics and allow for regulated drug release at the target site.…”

Section: Classification Of Ph‐responsive Polymersmentioning

confidence: 99%

“…2 HA can be made to crosslink with divinyl sulfone (DVS) in saline media, where the vinyl groups of DVS and hydroxyl groups of HA make covalent linkages. 62 These crosslinked matrices have exceptional mucoadhesive characteristics and allow for regulated drug release at the target site. Inside microfluidic channels, endothelial cell attachment can be produced by combining HA and collagen to form semi-interpenetrating networks.…”

Section: Hyaluronic Acidmentioning

confidence: 99%

pH‐responsive polymers for drug delivery: Trends and opportunities

Singh,

Nayak

2023

Journal of Polymer Science

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Polymer science has applications in biomedical engineering, prosthetics, surgical implants, and prospective pharmaceutical excipients for drug delivery. “Intelligent or Smart Polymers” are created for drug targeting either by derivatization of natural polymers or controlled radical polymerization of electrolytes. Their mode of action is governed by the environmental stimuli viz. temperature, pH, ionic concentration, magnetism, and so on. pH‐responsive polymers, because of their self‐assembling behavior, alter their solubility, conformation, surface activity, and hydrophilicity when exposed to a specific pH. The physiological pH varies from acidic nuclei to alkaline cytoplasm and highly acidic gastric juice to slightly alkaline plasma; thus, various polymers are under study for delivering small molecules, genes, peptides, enzymes, growth factors, and antibodies. The non‐invasive drug delivery routes like oral, ocular, nasal, pulmonary, transdermal, and rectal routes can be explored for targeting recombinant proteins, monoclonal antibodies, and small molecules with particular emphasis on the individual's physiological and pathological state. Further, these polymers can be designed into various architectures like dendrimers, liposomes, micelles, and metallic nanoparticles that can serve as drug reservoirs for sustaining drug release. The challenges in this field are the selection of biocompatible polymers with ease of synthesis and scale‐up, ensuring effective drug‐loading, and stability aspects, producing robust pharmacological data, and timely regulatory approvals. This review exclusively explores the physicochemical characteristics of pH‐responsive polymers, their categorization, various architectural entities, recent studies and patents, and their emerging applications concerning specific diseases.

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Dissecting the role of cancer‐associated fibroblast‐derived biglycan as a potential therapeutic target in immunotherapy resistance: A tumor bulk and single‐cell transcriptomic study

Zheng

Liang

Tang

et al. 2023

Clinical & Translational Med

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Introduction Cancer‐associated fibroblasts (CAFs) are correlated with the immunotherapy response. However, the culprits that link CAFs to immunotherapy resistance are still rarely investigated in real‐world studies. Objectives This study aims to systematically assess the landscape of fibroblasts in cancer patients by combining single‐cell and bulk profiling data from pan‐cancer cohorts. We further sought to decipher the expression, survival predictive value and association with immunotherapy response of biglycan (BGN), a proteoglycan in the extracellular matrix, in multiple cohorts. Methods Pan‐cancer tumor bulks and 27 single‐cell RNA sequencing cohorts were enrolled to investigate the correlations and crosstalk between CAFs and tumor or immune cells. Specific secreting factors of CAFs were then identified by expression profiling at tissue microdissection, isolated primary fibroblasts and single‐cell level. The role of BGN was further dissected in additional three bulk and five single‐cell profiling datasets from immunotherapy cohorts and validated in real‐world patients who have received PD‐1 blockade using immunohistochemistry and immunofluorescence. Results CAFs were closely correlated with immune components. Frequent crosstalk between CAFs and other cells was revealed by the CellChat analysis. Single‐cell regulatory network inference and clustering identified common and distinct regulators for CAFs across cancers. The BGN was determined to be a specific secreting factor of CAFs. The BGN served as an unfavourable indicator for overall survival and immunotherapy response. In the real‐world immunotherapy cohort, patients with high BGN levels presented a higher proportion of poor response compared with those with low BGN (46.7% vs. 11.8%) and a lower level of infiltrating CD8+ T cells was also observed. Conclusions We highlighted the importance of CAFs in the tumor microenvironment and revealed that the BGN, which is mainly derived from CAFs, may be applicable in clinical practice and serve as a therapeutic target in immunotherapy resistance.

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pH-responsive Sulfated Hyaluronic Acid Nanoparticles Targeting Tumor Cells and CAFs for the Treatment of Breast Cancer

Cited by 6 publications

References 47 publications

Shikonin-Loaded Hollow Fe-MOF Nanoparticles for Enhanced Microwave Thermal Therapy

Shikonin-Loaded Hollow Fe-MOF Nanoparticles for Enhanced Microwave Thermal Therapy

pH‐responsive polymers for drug delivery: Trends and opportunities

Dissecting the role of cancer‐associated fibroblast‐derived biglycan as a potential therapeutic target in immunotherapy resistance: A tumor bulk and single‐cell transcriptomic study

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