Salicylic acid-based hypoxia-responsive chemodynamic nanomedicines boost antitumor immunotherapy by modulating immunosuppressive tumor microenvironment

Sun, Kai; Yu, Jiaying; Hu, Jinzhong; Chen, Jian; Song, Jia; Chen, Zhuo; Cai, Zhuoer; Lu, Zhuoxuan; Zhang, Liming; Wang, Zhifei

doi:10.1016/j.actbio.2022.06.026

Cited by 22 publications

(22 citation statements)

References 44 publications

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“…Frontiers in Pharmacology frontiersin.org tumor infiltration of dendritic cells or cytotoxic T lymphocytes (Ahmadi et al, 2008;Liu et al, 2012;Sun et al, 2022). The emergence of cancer stem cells (CSCs) is related to different PGE 2 -related signaling pathways as well (Li et al, 2012;Wang et al, 2015;Fang et al, 2017).…”

Section: Inflammation and Cancer Developmentmentioning

confidence: 99%

“…Besides, PGE 2 promotes angiogenesis in cancer development ( Zhang and Daaka, 2011 ; Xu et al, 2014 ). Generation of immunosuppressive tumor microenvironment (TME) by regulating tumor-infiltrating immune cells is also achieved by PGE 2 , which includes stimulating type-2 macrophage polarization, inducing T cell dysfunction and preventing tumor infiltration of dendritic cells or cytotoxic T lymphocytes ( Ahmadi et al, 2008 ; Liu et al, 2012 ; Sun et al, 2022 ). The emergence of cancer stem cells (CSCs) is related to different PGE 2 -related signaling pathways as well ( Li et al, 2012 ; Wang et al, 2015 ; Fang et al, 2017 ).…”

Section: Inflammation and Cancer Developmentmentioning

confidence: 99%

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Targeting cancer-related inflammation with non-steroidal anti-inflammatory drugs: Perspectives in pharmacogenomics

Lai

Liu

et al. 2022

Front. Pharmacol.

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Inflammatory processes are essential for innate immunity and contribute to carcinogenesis in various malignancies, such as colorectal cancer, esophageal cancer and lung cancer. Pharmacotherapies targeting inflammation have the potential to reduce the risk of carcinogenesis and improve therapeutic efficacy of existing anti-cancer treatment. Non-steroidal anti-inflammatory drugs (NSAIDs), comprising a variety of structurally different chemicals that can inhibit cyclooxygenase (COX) enzymes and other COX-independent pathways, are originally used to treat inflammatory diseases, but their preventive and therapeutic potential for cancers have also attracted researchers’ attention. Pharmacogenomic variability, including distinct genetic characteristics among different patients, can significantly affect pharmacokinetics and effectiveness of NSAIDs, which might determine the preventive or therapeutic success for cancer patients. Hence, a more comprehensive understanding in pharmacogenomic characteristics of NSAIDs and cancer-related inflammation would provide new insights into this appealing strategy. In this review, the up-to-date advances in clinical and experimental researches targeting cancer-related inflammation with NSAIDs are presented, and the potential of pharmacogenomics are discussed as well.

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Section: Inflammation and Cancer Developmentmentioning

confidence: 99%

Section: Inflammation and Cancer Developmentmentioning

confidence: 99%

Targeting cancer-related inflammation with non-steroidal anti-inflammatory drugs: Perspectives in pharmacogenomics

Lai

Liu

et al. 2022

Front. Pharmacol.

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“…Hydrogels are three-dimensional meshed colloidal materials with many water molecules . Many natural polysaccharides such as chitosan, hyaluronate, and alginate-derived hydrogels, especially in situ formable hydrogels, have been fabricated and their application verified. − Because of their strong hygroscopicity, plasticity, and immunoregulation, they can be used as a multifunctional platform for drug release. − …”

Section: Introductionmentioning

confidence: 99%

Fabrication of an Injectable Star-polylactide/Thiolated Hyaluronate Hydrogel as a Double Drug-Delivery System for Cancer Treatment

Zhang

Fang

Tan³

et al. 2023

ACS Omega

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Unsatisfactory solid-tumor penetration or rapid metabolism of nanomaterials limits their therapeutic efficacy. Here, we designed an injectable thiolated hyaluronate (HA-SH) hydrogel as a stable drugreleasing platform for in situ tumor treatment. Biodegradable star-shaped polylactide (S-PLLA) was first synthesized and fabricated to porous microspheres to encapsulate hydrophobic curcumin (Cur@S-PLLA), which was then blended with hydrophilic doxorubicin (Dox) and the HA-SH precursor to form composite in situ formable hydrogels [Cur@S-PLLA/ (Dox)HA-SH]. The results showed that adding the microspheres improved the performance of the hydrogel, such as decreasing the gelation time from 1080 s to 960 s and also the swelling ratio. The mechanical strength increased from 27 to 45 kPa. In addition, the double drug system guaranteed a sustained release of drugs, releasing Dox at the early stage, with the continuous later release of Cur after gel swelling or S-PLLA degradation to achieve long-lasting tumor suppression, which inhibits the survival of cancer cells. The inhibitory effects of the hydrogels on MCF-7 were studied. The cell activity in the doubleloaded hydrogel was significantly lower than that of the control groups, and apparent dead cells appeared in 2 days and fewer living cells with time. Flow cytometry revealed that the Cur@S-PLLA/(Dox)HA-SH group had the highest apoptosis ratio of 86.60% at 12 h, and the drugs caused the cell cycle to be blocked in phase M to reduce cell division. In summary, the innovative release platform is expected to be used in long-lasting tumor suppression and provides more ideas for the design of drug carriers.

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“…7,11,12 However, one lethal vulnerability is that oral high-dose administration of COX-2/PGE 2 inhibitors can cause gastrointestinal bleeding and cardiac events. 13,14 Salicylic acid (SA), as the FDA approved antiinflammatory drug, is the functional ingredient of aspirin, which has been reported to restrain the activity of the COX-2/ PGE 2 axis. 9,10,15 Given its side effects limiting potential application in tumor therapy, nanoparticles-based drug delivery systems may be developed for the selective delivery of SA to tumor sites.…”

mentioning

confidence: 99%

“…Several previous studies have revealed the antitumor effect of COX-2/PGE 2 inhibitors to boost antitumor immunotherapy at high-dose administration. ,, However, one lethal vulnerability is that oral high-dose administration of COX-2/PGE 2 inhibitors can cause gastrointestinal bleeding and cardiac events. , Salicylic acid (SA), as the FDA approved anti-inflammatory drug, is the functional ingredient of aspirin, which has been reported to restrain the activity of the COX-2/PGE 2 axis. ,, Given its side effects limiting potential application in tumor therapy, nanoparticles-based drug delivery systems may be developed for the selective delivery of SA to tumor sites. Nanotherapy platforms have been particularly promising for tumor therapy over two decades.…”

mentioning

confidence: 99%

Pemetrexed–Poly(salicylic acid) Assemblies Reshape Immunosuppressive Tumor Microenvironment for Enhanced Chemo-immunotherapy

Sun

et al. 2023

ACS Materials Lett.

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Although chemotherapy can elicit antitumor immune response by the induction of immunogenic cell death (ICD), cyclooxygenase-2 (COX-2) and its downstream product prostaglandin E 2 (PGE 2 ), as negative immune regulators, impede the effect of antitumor immunotherapy. Herein, we rationally synthesized the COX-2/PGE 2 -inhibiting poly-(salicylic acid) (PSA) and constructed the esterase-responsive pemetrexed-conjugated PSA-PEG-FA prodrug nanoparticles (PEM−PPFs) by a self-assembly strategy, thereby inducing sufficient ICD, boosting the migration and maturation of dendritic cells (DCs), and activating cytotoxic T lymphocytes (CTLs) for enhanced chemo-immunotherapy. Meanwhile PEM−PPFs could reactivate intercellular reactive oxygen species (ROS) signaling to further potentiate tumor suppression, and recognize the overexpressed folate receptors (FRs) on the surface of colorectal cancer cells to reach tumor specific enrichment. Accordingly, this work presents a promising approach for the application of pemetrexed-conjugated poly(salicylic acid) nanomedicines for modulation of immunosuppressive tumor microenvironments, and inspires the design of functional old-drug polymers.

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Salicylic acid-based hypoxia-responsive chemodynamic nanomedicines boost antitumor immunotherapy by modulating immunosuppressive tumor microenvironment

Cited by 22 publications

References 44 publications

Targeting cancer-related inflammation with non-steroidal anti-inflammatory drugs: Perspectives in pharmacogenomics

Targeting cancer-related inflammation with non-steroidal anti-inflammatory drugs: Perspectives in pharmacogenomics

Fabrication of an Injectable Star-polylactide/Thiolated Hyaluronate Hydrogel as a Double Drug-Delivery System for Cancer Treatment

Pemetrexed–Poly(salicylic acid) Assemblies Reshape Immunosuppressive Tumor Microenvironment for Enhanced Chemo-immunotherapy

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