Trapping of Lipopolysaccharide to Promote Immunotherapy against Colorectal Cancer and Attenuate Liver Metastasis

Song, Wantong; Tiruthani, Karthik; Wang, Ying; Shen, Limei; Hu, Mengying; Dorosheva, Oleksandra; Qiu, Kunyu; Kinghorn, Karina; Liu, Rihe; Huang, Leaf

doi:10.1002/adma.201805007

Cited by 155 publications

(96 citation statements)

References 54 publications

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“…Now protein drugs play a vital role for treating a broad range of diseases, including cancer, metabolic disorders, and autoimmune diseases . Certain types of protein drugs like Atezolizumab, zinbryta, and cytochrome C have been approved by FDA for clinical use . Protein drugs have been widely applied in the treatment of various diseases attributed to their high specificity, great activity, and superior biocompatibility .…”

Section: Introductionmentioning

confidence: 99%

Glucose and pH Dual‐Responsive Nanogels for Efficient Protein Delivery

Song

Yang

et al. 2019

Macromolecular Bioscience

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Direct delivery of protein suffers from their in vitro and in vivo instability, immunogenicity, and a relatively short half‐life within the body. To overcome these challenges, pH and glucose dual‐responsive biodegradable nanogels comprised of dextran and poly(L‐glutamic acid)‐g‐methoxy poly‐(ethylene glycol)/phenyl boronic acid (PLG‐g‐mPEG/PBA) are designed. The cross‐linked network imparted drug‐loading efficacy of α‐amylase up to 55.6% and hyaluronidase up to 29.1%. In vitro protein release profiles reveal that the release of protein is highly dependent on the pH or glucose concentrations, that is, less amount of protein is released at pH 7.4 or healthy blood glucose level (1 mg mL−1 glucose), while quicker release of protein occurs at pH 5.5 or diabetic blood glucose level (above 3 mg mL−1 glucose). Circular dichroism spectra show that the secondary structure of released protein is maintained compared to naive protein. Overall, the nanogels have provided a simple and effective strategy to deliver protein.

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Section: Introductionmentioning

confidence: 99%

Glucose and pH Dual‐Responsive Nanogels for Efficient Protein Delivery

Song

Yang

et al. 2019

Macromolecular Bioscience

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“…Huang and co‐workers developed cationic liposome‐protamine‐HA nanoparticles to deliver siRNA to silence CD47 expression in solid tumors . Starting in 2017, the Huang group published a series of papers using a similar particle design (i.e., a liposome‐protamine‐DNA (LPD) nanoparticle) to deliver genes for various anticancer purposes, including those that encode for proteins that bind to (or trap): i) the immunosuppressive proteins PD‐L1 and C‐X‐C motif chemokine (CXCL)12, ii) the signaling protein Wnt family member 5A (Wnt5a), which has been implicated in inducing dendritic cell tolerance, iii) IL‐10, which is known to suppress dendritic cells from releasing IL‐12, to develop Th1 responses, iv) LPS, which relieved the immunosuppressive microenvironment and boosted anti‐PD‐L1 therapy against colorectal tumors, and v) CCR‐7, which is associated with the metastasis of breast cancer . The group also investigated the delivery of siRNA to silence high mobility group protein A1 (HMGA1), which is associated with immunosuppression .…”

Section: Nanoscale Materials For Immunotherapymentioning

confidence: 99%

Materials for Immunotherapy

et al. 2019

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Breakthroughs in materials engineering have accelerated the progress of immunotherapy in preclinical studies. The interplay of chemistry and materials has resulted in improved loading, targeting, and release of immunomodulatory agents. An overview of the materials that are used to enable or improve the success of immunotherapies in preclinical studies is presented, from immunosuppressive to proinflammatory strategies, with particular emphasis on technologies poised for clinical translation. The materials are organized based on their characteristic length scale, whereby the enabling feature of each technology is organized by the structure of that material. For example, the mechanisms by which i) nanoscale materials can improve targeting and infiltration of immunomodulatory payloads into tissues and cells, ii) microscale materials can facilitate cell‐mediated transport and serve as artificial antigen‐presenting cells, and iii) macroscale materials can form the basis of artificial microenvironments to promote cell infiltration and reprogramming are discussed. As a step toward establishing a set of design rules for future immunotherapies, materials that intrinsically activate or suppress the immune system are reviewed. Finally, a brief outlook on the trajectory of these systems and how they may be improved to address unsolved challenges in cancer, infectious diseases, and autoimmunity is presented.

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“…The morphological changes were all evaluated by TEM before and after incubation for 6 h. As shown in Figure F, before incubation, the surface of spores was smooth and consistent with the SEM characterization (Figure A,b). However, after 6 h incubation some of the protein‐like lamellar structures were observed around the spores, but without the NPs formulated, which was mainly attributed to the physiological growth behavior of spores . By contrast, when the DOX/SOR/Spore‐DA was incubated for 2 h, its surface began to get rough and some shedding substances were observed around the spores (Figure G).…”

Section: Methodsmentioning

confidence: 97%

A Probiotic Spore‐Based Oral Autonomous Nanoparticles Generator for Cancer Therapy

Song¹,

Zheng²,

Jia³

et al. 2019

Advanced Materials

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Spores, the dormant life forms of probiotics, can germinate to metabolically active vegetative cells with the disintegration of their hydrophobic protein coat in the intestinal microenvironment, which provides the possibility for the formation of nanoparticles (NPs) in vivo. Inspired by the natural physiological process of spores, herein, an oral autonomous NPs generator is developed to overcome the spatially variable gastrointestinal tract environment and multibiological barriers. Spores modified with deoxycholic acid (DA) and loaded with chemotherapeutic drugs (doxorubicin and sorafenib, DOX/SOR) serve as an autonomous production line of NPs, which can efficaciously protect the drugs passing through the rugged environment of the stomach and furthermore can be transported to the intestinal environment and colonized rapidly. Subsequently, the DOX/SOR/Spore‐DA NPs are produced by the autonomous NPs generator in the intestinal regions based on the disintegrated hydrophobic protein and the hydrophilic DA, and they can efficiently penetrate the epithelial cells via the bile acid pathway, increasing basolateral drug release. In vitro and in vivo studies confirm that this biological nanogenerator can autonomously produce substantial NPs in the intestine, providing a promising strategy for cancer therapy.

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Trapping of Lipopolysaccharide to Promote Immunotherapy against Colorectal Cancer and Attenuate Liver Metastasis

Cited by 155 publications

References 54 publications

Glucose and pH Dual‐Responsive Nanogels for Efficient Protein Delivery

Glucose and pH Dual‐Responsive Nanogels for Efficient Protein Delivery

Materials for Immunotherapy

A Probiotic Spore‐Based Oral Autonomous Nanoparticles Generator for Cancer Therapy

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