A Polymeric Nanogel-Based Treatment Regimen for Enhanced Efficacy and Sequential Administration of Synergistic Drug Combination in Pancreatic Cancer

Soni, Kruti S.; Thomas, Divya; Caffrey, Thomas C.; Mehla, Kamiya; Fan, Lei; O’Connell, Kelly A.; Sagar, Satish; Lele, Subodh M.; Hollingsworth, Michael A.; Radhakrishnan, Prakash; Bronich, Tatiana K.

doi:10.1124/jpet.118.255372

Cited by 19 publications

(7 citation statements)

References 36 publications

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“…In addition, antibodies can be applied not only as the ligands but also as therapeutic agents in cancer treatment; for instance, antibody-dependent cell-mediated cytotoxicity (ADCC) was indicated to inhibit cellular signaling pathways related to tumor growth and initiation [69,70]. In a previous report, an anti-STn antigen-specific antibody was employed to modify nanogels because of the aberrant expression of Sialyl Tn (STn) antigen in pancreatic ductal adenocarcinoma (PDAC), resulting in the effective accumulation of drugs in tumor tissues, which not only improved the antitumor effect, but also implied a promising target for PDAC [71].…”

Section: Antibody Conjugationmentioning

confidence: 99%

Nanogel: A Versatile Nano-Delivery System for Biomedical Applications

et al. 2020

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Nanogel-based nanoplatforms have become a tremendously promising system of drug delivery. Nanogels constructed by chemical crosslinking or physical self-assembly exhibit the ability to encapsulate hydrophilic or hydrophobic therapeutics, including but not limited to small-molecule compounds and proteins, DNA/RNA sequences, and even ultrasmall nanoparticles, within their 3D polymer network. The nanosized nature of the carriers endows them with a specific surface area and inner space, increasing the stability of loaded drugs and prolonging their circulation time. Reactions or the cleavage of chemical bonds in the structure of drug-loaded nanogels have been shown to trigger the controlled or sustained drug release. Through the design of specific chemical structures and different methods of production, nanogels can realize diverse responsiveness (temperature-sensitive, pH-sensitive and redox-sensitive), and enable the stimuli-responsive release of drugs in the microenvironments of various diseases. To improve therapeutic outcomes and increase the precision of therapy, nanogels can be modified by specific ligands to achieve active targeting and enhance the drug accumulation in disease sites. Moreover, the biomembrane-camouflaged nanogels exhibit additional intelligent targeted delivery features. Consequently, the targeted delivery of therapeutic agents, as well as the combinational therapy strategy, result in the improved efficacy of disease treatments, though the introduction of a multifunctional nanogel-based drug delivery system.

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Section: Antibody Conjugationmentioning

confidence: 99%

Nanogel: A Versatile Nano-Delivery System for Biomedical Applications

et al. 2020

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“…For targeted administration, the STn antigen, which is abundantly expressed in cancer cells, was conjugated to nanogel-encapsulated cisplatin using the TKH2 monoclonal antibody. When gemcitabine is administered in conjunction with TKH2-functionalized cisplatin-loaded nanogels, tumor development may be effectively reduced in vitro and in vivo [ 126 ]. One other team has created a biocompatible nanoparticle that selectively transports 5-fluorouracil and Paclitaxel to SLeA-expressing gastric cancer cells while avoiding healthy tissue.…”

Section: Glycans As Therapeutic Targets In Renal Cancermentioning

confidence: 99%

Glycosylation in Renal Cell Carcinoma: Mechanisms and Clinical Implications

Zhu

Al-Danakh

Zhang

et al. 2022

Cells

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Renal cell carcinoma (RCC) is one of the most prevalent malignant tumors of the urinary system, accounting for around 2% of all cancer diagnoses and deaths worldwide. Clear cell RCC (ccRCC) is the most prevalent and aggressive histology with an unfavorable prognosis and inadequate treatment. Patients’ progression-free survival is considerably improved by surgery; however, 30% of patients develop metastases following surgery. Identifying novel targets and molecular markers for RCC prognostic detection is crucial for more accurate clinical diagnosis and therapy. Glycosylation is a critical post-translational modification (PMT) for cancer cell growth, migration, and invasion, involving the transfer of glycosyl moieties to specific amino acid residues in proteins to form glycosidic bonds through the activity of glycosyltransferases. Most cancers, including RCC, undergo glycosylation changes such as branching, sialylation, and fucosylation. In this review, we discuss the latest findings on the significance of aberrant glycans in the initiation, development, and progression of RCC. The potential biomarkers of altered glycans for the diagnosis and their implications in RCC have been further highlighted.

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“…In recent work by members of our team, temperature- and pH-responsive pentablock copolymers, consisting of a temperature-responsive Pluronic ® F127 middle block and pH-responsive poly(diethylaminoethylmethacrylate) (PDEAEM) end blocks were developed for dual delivery of miR-345 and GEM 121 . Recent reports have also discussed the use of nanogels as targeted nanomedicines to increase treatment effectiveness and improve outcomes of PC therapy 122 , 123 .…”

Section: Nanocarrier-based Delivery Of Therapeutic Imaging and Theran...mentioning

confidence: 99%

Nanocarriers for pancreatic cancer imaging, treatments, and immunotherapies

Liu¹,

Kshirsagar²,

Gautam³

et al. 2022

Theranostics

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Pancreatic tumors are highly desmoplastic and immunosuppressive. Delivery and distribution of drugs within pancreatic tumors are compromised due to intrinsic physical and biochemical stresses that lead to increased interstitial fluid pressure, vascular compression, and hypoxia. Immunotherapy-based approaches, including therapeutic vaccines, immune checkpoint inhibition, CAR-T cell therapy, and adoptive T cell therapies, are challenged by an immunosuppressive tumor microenvironment. Together, extensive fibrosis and immunosuppression present major challenges to developing treatments for pancreatic cancer. In this context, nanoparticles have been extensively studied as delivery platforms and adjuvants for cancer and other disease therapies. Recent advances in nanotechnology have led to the development of multiple nanocarrier-based formulations that not only improve drug delivery but also enhance immunotherapy-based approaches for pancreatic cancer. This review discusses and critically analyzes the novel nanoscale strategies that have been used for drug delivery and immunomodulation to improve treatment efficacy, including newly emerging immunotherapy-based approaches. This review also presents important perspectives on future research directions that will guide the rational design of novel and robust nanoscale platforms to treat pancreatic tumors, particularly with respect to targeted therapies and immunotherapies. These insights will inform the next generation of clinical treatments to help patients manage this debilitating disease and enhance survival rates.

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A Polymeric Nanogel-Based Treatment Regimen for Enhanced Efficacy and Sequential Administration of Synergistic Drug Combination in Pancreatic Cancer

Cited by 19 publications

References 36 publications

Nanogel: A Versatile Nano-Delivery System for Biomedical Applications

Nanogel: A Versatile Nano-Delivery System for Biomedical Applications

Glycosylation in Renal Cell Carcinoma: Mechanisms and Clinical Implications

Nanocarriers for pancreatic cancer imaging, treatments, and immunotherapies

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