An injectable hydrogel using an immunomodulating gelator for amplified tumor immunotherapy by blocking the arginase pathway

Ren, Xiaomeng; Wang, Ningning; Zhou, Yaxin; Song, Aixin; Jin, Guoxia; Li, Zhonghao; Luan, Yuxia

doi:10.1016/j.actbio.2021.01.041

Cited by 120 publications

(67 citation statements)

References 55 publications

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“…[23][24][25][26] Up to now, a variety of carriers have been investigated for the co-delivery of drugs and genes/photosensitizers in anti-cancer trails, including cationic polymers, liposomes, human serum albumin, hydrogels and inorganic nanoparticles. [27][28][29][30][31][32][33] Among them, polymeric micelles formed by amphiphilic block copolymers have gained more attention due to their unique properties such as the core/shell structure, excellent stability, and ideal encapsulation and delivery efficiency of hydrophobic drugs. [34][35][36][37] Polyethylene glycol-polylactic acid (PEG-PLA), one of the most prominent amphiphilic block copolymers, can self-assemble into micelles with core/shell structure in aqueous phase.…”

Section: Introductionmentioning

confidence: 99%

Nucleolin-Targeting AS1411 Aptamer-Modified Micelle for the Co-Delivery of Doxorubicin and miR-519c to Improve the Therapeutic Efficacy in Hepatocellular Carcinoma Treatment

Liang¹,

Wang²,

Shi³

et al. 2021

IJN

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Background: Multidrug resistance (MDR) has emerged to be a major hindrance in cancer therapy, which contributes to the reduced sensitivity of cancer cells toward chemotherapeutic drugs mainly owing to the over-expression of drug efflux transporters. The combination of gene therapy and chemotherapy has been considered as a potential approach to improve the anti-cancer efficacy by reversing the MDR effect. Materials and Methods: The AS1411 aptamer-functionalized micelles were constructed through an emulsion/solvent evaporation strategy for the simultaneous co-delivery of doxorubicin and miR-519c. The therapeutic efficacy and related mechanism of micelles were explored based on the in vitro and in vivo active targeting ability and the suppression of MDR, using hepatocellular carcinoma cell line HepG2 as a model. Results:The micelle was demonstrated to possess favorable cellular uptake and tumor penetration ability by specifically recognizing the nucleolin in an AS1411 aptamerdependent manner. Further, the intracellular accumulation of doxorubicin was significantly improved due to the suppression of ABCG2-mediated drug efflux by miR-519c, resulting in the efficient inhibition of tumor growth. Conclusion:The micelle-mediated co-delivery of doxorubicin and miR-519c provided a promising strategy to obtain ideal anti-cancer efficacy through the active targeting function and the reversion of MDR.

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Section: Introductionmentioning

confidence: 99%

Nucleolin-Targeting AS1411 Aptamer-Modified Micelle for the Co-Delivery of Doxorubicin and miR-519c to Improve the Therapeutic Efficacy in Hepatocellular Carcinoma Treatment

Liang¹,

Wang²,

Shi³

et al. 2021

IJN

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“…Suitable carriers based on hydrogels [ 19 , 20 ], polysaccharide complexes [ 21 ], and liposomes [ 22 , 23 , 24 ] have been designed as delivery systems of poorly soluble nutraceuticals allowing their transport in aqueous media and in situ delivery, while avoiding possible undesired side effects. SLNs show greater biocompatibility, lower toxicity, and better delivery of lipophilic drugs with respect to hydrogel.…”

Section: Introductionmentioning

confidence: 99%

Solid Lipid Nanoparticles Produced via a Coacervation Method as Promising Carriers for Controlled Release of Quercetin

et al. 2021

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Quercetin is a poorly water-soluble flavonoid with many benefits to human health. Besides the natural food resources that may provide Quercetin, the interest in delivery systems that could enhance its bioavailability in the human body has seen growth in recent years. Promising delivery system candidates are represented by Solid Lipid Nanoparticles (SLNs) which are composed of well-tolerated compounds and provide a relatively high encapsulation efficiency and suitable controlled release. In this study, Quercetin-loaded and negatively charged Solid Lipid Nanoparticles were synthesized based on a coacervation method, using stearic acid as a core lipid and Arabic Gum as a stabilizer. Samples were qualitatively characterized by Dynamic light scattering (DLS), Zeta Potential, Surface infrared spectroscopy (FTIR-ATR), and Time of flight secondary ion mass spectrometry (ToF-SIMS). Encapsulation efficiency, drug release, and antioxidant effect against ABTS•+ were evaluated in vitro by UV–VIS spectrophotometry.

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“…Tumor cells avoid the immune response in a process known as immune evasion (Schreiber et al., 2011 ; Zhou et al., 2020 ; Ren et al., 2021 ; Zhou et al., 2021 ). The immune escape of tumor cells is divided into three stages: (1) Elimination phase: at this stage, antigen-presenting cells (APC) monitor the antigens expressed by tumors and present them to cytotoxic T cells through major histocompatibility complex (MHC) class I molecules, which is the first signal of T cell activation, then the molecule CD80/CD86 on the surface of APC combines the costimulatory molecule CD28 on the surface of T cells which forms a costimulatory signal (Murakami & Riella, 2014 ), thereby cytotoxic T cells are activated, they target and eliminate tumor cells by secreting perforin, granzyme or by the death ligand/death receptor pathway (Martinez-Lostao et al., 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Lysosome activable polymeric vorinostat encapsulating PD-L1KD for a combination of HDACi and immunotherapy

Hou

Wang

et al. 2021

Drug Delivery

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PD-1/PD-L1 blocking therapy has become one of the most promising methods in the field of tumor treatment. However, it encounters the challenge of immune escape due to the exhaustion of T cells. Studies have shown that the epigenetic regulation drug histone deacetylase inhibitor (HDACi) may be able to reverse exhausted T cells by changing the epigenetic transcription program. Therefore, the combination of epigenetic therapy and PD-1/PD-L1 blockade therapy is expected to reverse the immune escape, whereas the overriding goal should aim at the spontaneous release and synergy of PD-1/PD-L1 blocking siRNA and HDACi. In this study, we develop PDDS{polyethylene glycol-b-asparaginate(diethylenetriamine-vorinostat), (PEG-b-P[Asp(DET-SAHA) n ] PPDS)}encapsulating siRNA-PD-L1to provide micelles siRNA-PD-L1-loaded micelles (siRNA@PPDS). Transmission electron microscope (TEM) images demonstrate that siRNA@PPDS micelles presented spherical morphology with a size of about 120 nm; hydrodynamic data analysis indicates pH sensitivity of siRNA@PPDS micelles. The experiments reveal that siRNA@PPDS micelles could be well uptaken by the tumor cells to silence the expression of PD-L1 protein in a dose-dependent manner; compared with the free SAHA, the SAHA-loaded micelles PPDS show higher cytotoxicity to induce tumor cell apoptosis and block cell cycle in G1 phase on melanoma-bearing mice, siRNA@PPDS has shown outstanding inhibition of tumor growth and pulmonary metastasis. By comprehensively activating the immune system, lysosome activable polymeric vorinostat encapsulating PD-L1KD for the combination therapy of PD-L1-KD and HDACIs can be an effective strategy to reverse the unresponsiveness of immune checkpoint inhibitors and a promising treatment to inhibit tumor growth, recurrence, and metastasis in clinic.

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An injectable hydrogel using an immunomodulating gelator for amplified tumor immunotherapy by blocking the arginase pathway

Cited by 120 publications

References 55 publications

Nucleolin-Targeting AS1411 Aptamer-Modified Micelle for the Co-Delivery of Doxorubicin and miR-519c to Improve the Therapeutic Efficacy in Hepatocellular Carcinoma Treatment

Nucleolin-Targeting AS1411 Aptamer-Modified Micelle for the Co-Delivery of Doxorubicin and miR-519c to Improve the Therapeutic Efficacy in Hepatocellular Carcinoma Treatment

Solid Lipid Nanoparticles Produced via a Coacervation Method as Promising Carriers for Controlled Release of Quercetin

Lysosome activable polymeric vorinostat encapsulating PD-L1KD for a combination of HDACi and immunotherapy

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