Delivery of triptolide with reduction-sensitive polymer nanoparticles for liver cancer therapy on patient-derived xenografts models

He, Meizi; Yu, Ling; Yang, Yuanyuan; Zou, Binhua; Wen, Ming‐Shien; Yu, Meng; Lu, Jiandong; Xiong, Guoliang; Yu, Zhiqiang; Li, Aimin

doi:10.1016/j.cclet.2020.05.034

Cited by 83 publications

(37 citation statements)

References 29 publications

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“…Mouse blood was centrifuged at 4 ℃ for 10 min at 4,000 rpm, and serum was collected and stored at − 20 °C for analysis. The levels of blood AST, ALT, BUN, and Cr were detected using a blood biochemical analyzer [ 40 ].…”

Section: Methodsmentioning

confidence: 99%

“…Additionally, redox-responsive nanoparticles have also aroused considerable enthusiasm because of the high intracellular concentration of glutathione (GSH) (approximately 2–10 mM) in tumors in comparison with that in the extracellular environment (2–20 μM) [ 19 ]. Several pH- [ 20 ] or redox-responsive [ 21 , 22 ] nanoparticles loading TPL have been reported to benefit the delivery of TPL with enhanced antitumor effects and reduced toxicity to normal tissues. Nonetheless, although these functional nano-vehicles including tumor-targeting/ pH-sensitive/ redox-responsive NPs were used for the encapsulation of TPL, few studies were implemented to combine the advantages of tumor-targeting and tumor microenvironment responsive drug release.…”

Section: Introductionmentioning

confidence: 99%

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Novel CD44-targeting and pH/redox-dual-stimuli-responsive core–shell nanoparticles loading triptolide combats breast cancer growth and lung metastasis

Shi

Ren

et al. 2021

J Nanobiotechnol

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Background The toxicity and inefficient delivery of triptolide (TPL) in tumor therapy have greatly limited the clinical application. Thus, we fabricated a CD44-targeting and tumor microenvironment pH/redox-sensitive nanosystem composed of hyaluronic acid-vitamin E succinate and poly (β-amino esters) (PBAEss) polymers to enhance the TPL-mediated suppression of breast cancer proliferation and lung metastasis. Results The generated TPL nanoparticles (NPs) had high drug loading efficiency (94.93% ± 2.1%) and a desirable average size (191 nm). Mediated by the PBAEss core, TPL/NPs displayed a pH/redox-dual-stimuli-responsive drug release profile in vitro. Based on the hyaluronic acid coating, TPL/NPs exhibited selective tumor cellular uptake and high tumor tissue accumulation capacity by targeting CD44. Consequently, TPL/NPs induced higher suppression of cell proliferation, blockage of proapoptotic and cell cycle activities, and strong inhibition of cell migration and invasion than that induced by free TPL in MCF-7 and MDA-MB-231 cells. Importantly, TPL/NPs also showed higher efficacy in shrinking tumor size and blocking lung metastasis with decreased systemic toxicity in a 4T1 breast cancer mouse model at an equivalent or lower TPL dosage compared with that of free TPL. Histological immunofluorescence and immunohistochemical analyses in tumor and lung tissue revealed that TPL/NPs induced a high level of apoptosis and suppressed expression of matrix metalloproteinases, which contributed to inhibiting tumor growth and pulmonary metastasis. Conclusion Collectively, our results demonstrate that TPL/NPs, which combine tumor active targeting and pH/redox-responsive drug release with proapoptotic and antimobility effects, represent a promising candidate in halting breast cancer progression and metastasis while minimizing systemic toxicity. Graphic Abstract

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Novel CD44-targeting and pH/redox-dual-stimuli-responsive core–shell nanoparticles loading triptolide combats breast cancer growth and lung metastasis

Shi

Ren

et al. 2021

J Nanobiotechnol

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Section: Applicationsmentioning

confidence: 99%

“…By engineering the polymers, nanoparticles can also achieve target drug delivery by actively delivering the particles to the diseased tissues through enhanced permeability and retention (EPR) effect. [64,65,66] Lale et al prepared AS1411 aptamer and folic acid functionalized pH-responsive pPEGMA-PCL-pPEGMA polymeric nanoparticles via atom transfer radical polymerization (ATRP). The folate-mediated endocytosis improves the targeting efficiency of the nanoparticles to the cancer cells and their accumulation.…”

Section: Applications Of Nanoparticlesmentioning

confidence: 99%

Diverse Particle Carriers Prepared by Co‐Precipitation and Phase Separation: Formation and Applications

Sun

Ren

et al. 2020

ChemPlusChem

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Nanoparticles with diverse structures and unique properties have attracted increasing attention for their widespread applications. Co‐precipitation under rapid mixing is an effective method to obtained biocompatible nanoparticles and diverse particle carriers are achieved by controlled phase separation via interfacial tensions. In this Minireview, we summarize the underlying mechanism of co‐precipitation and show that rapid mixing is important to ensure co‐precipitation. In the binary polymer system, the particles can form four different morphologies, including occluded particle, core‐shell capsule, dimer particle, and heteroaggregate, and we demonstrate that the final morphology could be controlled by surface tensions through surfactant, polymer composition, molecular weight, and temperature. The applications of occluded particles, core‐shell capsules and dimer particles prepared by co‐precipitation or microfluidics upon the regulation of interfacial tensions are discussed in detail, and show great potential in the areas of functional materials, colloidal surfactants, drug delivery, nanomedicine, bio‐imaging, displays, and cargo encapsulation.

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“…Moreover, a patient-derived tumor xenograft (PDX) model of HCC (PDXHCC) was used to explore the potential of TP/Ce6-LP under light irradiation for effective anti-tumor therapy. The PDX model had the following advantages that could not only maintain biological stability and intratumoral heterogeneity, but also regenerated a microenvironment similar to the human tumor (for example, tumor vasculature, extracellular matrix and macrophages) 34 , 35 . Therefore, the PDX model could more accurately evaluate the therapeutic effect of nanomedicine.…”

Section: Introductionmentioning

confidence: 99%

Synergetic delivery of triptolide and Ce6 with light-activatable liposomes for efficient hepatocellular carcinoma therapy

Wang

et al. 2021

Acta Pharmaceutica Sinica B

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124

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Hepatocellular carcinoma (HCC) has been known as the second common leading cancer worldwide, as it responds poorly to both chemotherapy and medication. Triptolide (TP), a diterpenoid triepoxide, is a promising treatment agent for its effective anticancer effect on multiple cancers including HCC. However, its clinical application has been limited owing to its severe systemic toxicities, low solubility, and fast elimination in the body. Therefore, to overcome the above obstacles, photo-activatable liposomes (LP) integrated with both photosensitizer Ce6 and chemotherapeutic drug TP (TP/Ce6-LP) was designed in the pursuit of controlled drug release and synergetic photodynamic therapy in HCC therapy. The TP encapsulated in liposomes accumulated to the tumor site due to the enhanced permeability and retention (EPR) effect. Under laser irradiation, the photosensitizer Ce6 generated reactive oxygen species (ROS) and further oxidized the unsaturated phospholipids. In this way, the liposomes were destroyed to release TP. TP/Ce6-LP with NIR laser irradiation (TP/Ce6-LP+L) showed the best anti-tumor effect both in vitro and in vivo on a patient derived tumor xenograft of HCC (PDXHCC). TP/Ce6-LP significantly reduced the side effects of TP. Furthermore, TP/Ce6-LP+L induced apoptosis through a caspase-3/PARP signaling pathway. Overall, TP/Ce6-LP+L is a novel potential treatment option in halting HCC progression with attenuated toxicity.

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Delivery of triptolide with reduction-sensitive polymer nanoparticles for liver cancer therapy on patient-derived xenografts models

Cited by 83 publications

References 29 publications

Novel CD44-targeting and pH/redox-dual-stimuli-responsive core–shell nanoparticles loading triptolide combats breast cancer growth and lung metastasis

Novel CD44-targeting and pH/redox-dual-stimuli-responsive core–shell nanoparticles loading triptolide combats breast cancer growth and lung metastasis

Diverse Particle Carriers Prepared by Co‐Precipitation and Phase Separation: Formation and Applications

Synergetic delivery of triptolide and Ce6 with light-activatable liposomes for efficient hepatocellular carcinoma therapy

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