4 results on '"Keman Cheng"'
Search Results
2. Sequentially Responsive Therapeutic Peptide Assembling Nanoparticles for Dual-Targeted Cancer Immunotherapy
- Author
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Tianjiao Ji, Shefang Ye, Ying Zhao, Lei Ren, Gregory J. Anderson, Guangjun Nie, Bin Wang, Xiao Zhao, Yanping Ding, Yinlong Zhang, Keman Cheng, and Huanhuan Wu
- Subjects
medicine.medical_treatment ,Cell ,Mice, Nude ,Bioengineering ,Peptide ,02 engineering and technology ,Isoindoles ,010402 general chemistry ,01 natural sciences ,B7-H1 Antigen ,Mice ,Drug Delivery Systems ,Immune system ,Cancer immunotherapy ,Tumor Microenvironment ,medicine ,Animals ,Cytotoxic T cell ,General Materials Science ,Melanoma ,chemistry.chemical_classification ,Mechanical Engineering ,Imidazoles ,General Chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,medicine.disease ,Small molecule ,0104 chemical sciences ,medicine.anatomical_structure ,chemistry ,Delayed-Action Preparations ,Nucleic acid ,Cancer research ,Nanoparticles ,Immunotherapy ,Peptides ,0210 nano-technology - Abstract
Combination therapeutic regimen is becoming a primary direction for current cancer immunotherapy to broad the antitumor response. Functional nanomaterials offer great potential for steady codelivery of various drugs, especially small molecules, therapeutic peptides, and nucleic acids, thereby realizing controllable drug release, increase of drug bioavailability, and reduction of adverse effects. Herein, a therapeutic peptide assembling nanoparticle that can sequentially respond to dual stimuli in the tumor extracellular matrix was designed for tumor-targeted delivery and on-demand release of a short d-peptide antagonist of programmed cell death-ligand 1 (DPPA-1) and an inhibitor of idoleamine 2,3-dioxygenase (NLG919). By concurrent blockade of immune checkpoints and tryptophan metabolism, the nanoformulation increased the level of tumor-infiltrated cytotoxic T cells and in turn effectively inhibited melanoma growth. To achieve this, an amphiphilic peptide, consisting of a functional 3-diethylaminopropyl i...
- Published
- 2018
3. Tumor-Specific Silencing of Tissue Factor Suppresses Metastasis and Prevents Cancer-Associated Hypercoagulability
- Author
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Tianjiao Ji, Jing Wang, Chunzhi Di, Guangjun Nie, Long Chen, Yinlong Zhang, Keman Cheng, Yingqiu Qi, Ying Zhao, Suping Li, Yongwei Wang, Xiao Zhao, and Shaoli Liu
- Subjects
Small interfering RNA ,Lung Neoplasms ,Mice, Nude ,Bioengineering ,02 engineering and technology ,Metastasis ,Thromboplastin ,Tissue factor ,Circulating tumor cell ,Cell Line, Tumor ,Medicine ,Gene silencing ,Animals ,Humans ,Thrombophilia ,General Materials Science ,Platelet activation ,Gene Silencing ,Neoplasm Metastasis ,RNA, Small Interfering ,Tumor microenvironment ,business.industry ,Mechanical Engineering ,Cancer ,Thrombosis ,General Chemistry ,Neoplasms, Experimental ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,medicine.disease ,Neoplastic Cells, Circulating ,Neoplasm Proteins ,Gene Expression Regulation, Neoplastic ,Cancer research ,Nanoparticles ,Female ,0210 nano-technology ,business - Abstract
Within tumors, the coagulation-inducing protein tissue factor (TF), a major initiator of blood coagulation, has been shown to play a critical role in the hematogenous metastasis of tumors, due to its effects on tumor hypercoagulability and on the mediation of interactions between platelets and tumor cells. Targeting tumor-associated TF has therefore great therapeutic potential for antimetastasis therapy and preventing thrombotic complication in cancer patients. Herein, we reported a novel peptide-based nanoparticle that targets delivery and release of small interfering RNA (siRNA) into the tumor site to silence the expression of tumor-associated TF. We showed that suppression of TF expression in tumor cells blocks platelet adhesion surrounding tumor cells in vitro. The downregulation of TF expression in intravenously administered tumor cells (i.e., simulated circulating tumor cells [CTCs]) prevented platelet adhesion around CTCs and decreased CTCs survival in the lung. In a breast cancer mouse model, siRNA-containing nanoparticles efficiently attenuated TF expression in the tumor microenvironment and remarkably reduced the amount of lung metastases in both an experimental lung metastasis model and tumor-bearing mice. What's more, this strategy reversed the hypercoagulable state of the tumor bearing mice by decreasing the generation of thrombin-antithrombin complexes (TAT) and activated platelets, both of which are downstream products of TF. Our study describes a promising approach to combat metastasis and prevent cancer-associated thrombosis, which advances TF as a therapeutic target toward clinic applications.
- Published
- 2019
4. Sequentially Responsive Therapeutic Peptide Assembling Nanoparticles for Dual-Targeted Cancer Immunotherapy.
- Author
-
Keman Cheng, Yanping Ding, Ying Zhao, Shefang Ye, Xiao Zhao, Yinlong Zhang, Tianjiao Ji, Huanhuan Wu, Bin Wang, Anderson, Gregory J., Lei Ren, and Guangjun Nie
- Subjects
- *
CANCER immunotherapy , *MOLECULAR self-assembly , *ANTINEOPLASTIC agents , *NANOSTRUCTURED materials , *NANOMEDICINE , *CONTROLLED release drugs - Abstract
Combination therapeutic regimen is becoming a primary direction for current cancer immunotherapy to broad the antitumor response. Functional nanomaterials offer great potential for steady codelivery of various drugs, especially small molecules, therapeutic peptides, and nucleic acids, thereby realizing controllable drug release, increase of drug bioavailability, and reduction of adverse effects. Herein, a therapeutic peptide assembling nanoparticle that can sequentially respond to dual stimuli in the tumor extracellular matrix was designed for tumor-targeted delivery and on-demand release of a short d-peptide antagonist of programmed cell death-ligand 1 (DPPA-1) and an inhibitor of idoleamine 2,3-dioxygenase (NLG919). By concurrent blockade of immune checkpoints and tryptophan metabolism, the nanoformulation increased the level of tumor-infiltrated cytotoxic T cells and in turn effectively inhibited melanoma growth. To achieve this, an amphiphilic peptide, consisting of a functional 3-diethylaminopropyl isothiocyanate (DEAP) molecule, a peptide substrate of matrix metalloproteinase-2 (MMP-2), and DPPA-1, was synthesized and coassembled with NLG919. The nanostructure swelled when it encountered the weakly acidic tumor niche where DEAP molecules were protonated, and further collapsed due to the cleavage of the peptide substrate by MMP-2 that is highly expressed in tumor stroma. The localized release of DPPA-1 and NLG919 created an environment which favored the survival and activation of cytotoxic T lymphocytes, leading to the slowdown of melanoma growth and increase of overall survival. Together, this study offers new opportunities for dual-targeted cancer immunotherapy through functional peptide assembling nanoparticles with design features that are sequentially responsive to the multiple hallmarks of the tumor microenvironment. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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