Fabrication of dual responsive co-delivery system based on three-armed peptides for tumor therapy

Chen, Si; Lei, Qi; Li, Shi‐Ying; Qin, Si‐Yong; Jia, Hui‐Zhen; Cheng, Yin‐Jia; Zhang, Xian‐Zheng

doi:10.1016/j.biomaterials.2016.03.031

Cited by 41 publications

(29 citation statements)

References 41 publications

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“…Disulfide bonds physiologically respond to the intracellular GSH, which has been widely applied in smart drug delivery systems [15,[31][32][33]. Since the concentration of intracellular GSH (1-11 mM) for dissociating the disulfide bonds within the framework of PMOs is much higher than that of extracellular (10 µM) in cancer cells, the payload release can be triggered in vitro [34,35].…”

Section: Resultsmentioning

confidence: 99%

Tri-stimuli-responsive biodegradable theranostics for mild hyperthermia enhanced chemotherapy

et al. 2017

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The combination of hyperthermia and chemotherapy is able to greatly enhance the treatment efficacy mainly due to the synergistic interactions between these two treatments. In this study, we propose a new concept of mild hyperthermia enhanced chemotherapy to explore and validate the synergistic mechanism in vitro and in vivo. To do this, a novel kind of biodegradable nanotheranostics based on copper sulfide doped periodic mesoporous organosilica nanoparticles (CuS@PMOs) was constructed via an in situ growth method for light-triggered mild hyperthermia and drug delivery. The as-prepared CuS@PMOs exhibit a high doxorubicin (DOX) loading capacity of 470 mg/g. The DOX release from CuS@PMOs can be precisely controlled by three stimuli, including intracellular glutathione (GSH), acidic environment in tumor cells, and external laser irradiation. Most intriguingly, mild hyperthermia induced by laser-irradiated CuS nanoparticles can dramatically improve the cell uptake of nanotheranostics both in vitro and in vivo, thus significantly enhancing the chemotherapeutic efficacy for complete tumor growth suppression without recurrence. Meanwhile, the fluorescence recovery following the DOX release can be used as an indicator to monitor the chemotherapeutic progress.

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Section: Resultsmentioning

confidence: 99%

Tri-stimuli-responsive biodegradable theranostics for mild hyperthermia enhanced chemotherapy

et al. 2017

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“…On the other hand, one of the disadvantages of plasmid delivery is the fact that they need to reach the cell nucleus to be effective, which is harder to achieve than cytosol delivery. Although plasmid DNA has been successfully used in combination with small molecule therapeutics, achieving a clinical effect by plasmid delivery alone still needs to be improved. Plasmid DNA delivery by cell penetrating peptides for tumor treatment is still a challenge; CPPs need to be tumor specific to achieve safe and efficient cancer therapy through systemic delivery.…”

Section: Discussionmentioning

confidence: 99%

Tumor gene therapy by systemic delivery of plasmid DNA with cell-penetrating peptides

et al. 2018

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Gene therapy is a prospective strategy for treating cancer. However, finding efficient and tumor‐specific gene delivery vectors remains an issue. Tumor responsive cell‐penetrating peptide (CPP) PepFect144 (PF144) has previously been shown to deliver reporter gene encoding plasmid DNA specifically into tumors upon systemic administration, but its capability to reduce tumor growth has not yet been evaluated. Here, we study the potential of PF144‐based anti‐angiogenic gene delivery to inhibit tumor growth by silencing vascular endothelial growth factor (VEGF) expression in tumors. This approach led to the inhibition of tumor growth in both the HT1080 fibrosarcoma model and orthotopic 4T1 breast tumor model. We additionally saw that the addition of αvβ3 integrin targeting did not further improve the tumor sensitive CPPs. Our results suggest that activatable cell‐penetrating peptide PF144 is a promising nonviral plasmid DNA delivery vector for cancer treatment.

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“…Confocal laser scanning microscope (CLSM) was employed to study in vitro cellular uptake [29]. HepG2 cells were incubated at 2 × 10 5 per well in 6-well plates (Costar, Corning, NY, USA) for 24 h. After the medium was removed, DOX⋅HCl or DOX-loaded GA-GEL micelles (equivalent DOX concentration: 5 g/mL) were added.…”

Section: In Vitro Cellularmentioning

confidence: 99%

Preparation and Evaluation of Doxorubicin-Loaded Micelles Based on Glycyrrhetinic Acid Modified Gelatin Conjugates for Targeting Hepatocellular Carcinoma

Fan

Yan

et al. 2018

Journal of Nanomaterials

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Hepatocellular carcinoma (HCC) is one of the most prevalent fatal diseases and the incidence of HCC is increasing worldwide. Polymeric micelles with targeting groups have drawn great attention as carriers for drug delivery in HCC therapy. Herein, novel glycyrrhetinic acid modified gelatin (GA-GEL) conjugates with three substitution degrees were synthesized and characterized. Doxorubicin (DOX) was applied as a model drug. DOX-loaded GA-GEL (DOX/GA-GEL) micelles were prepared by an emulsionsolvent evaporation method. The mean diameters of DOX/GA-GEL micelles were in the range of 195-235 nm. The encapsulation efficiency of DOX/GA-GEL micelles was 63.6%-96.2%, and the loading content was 8.3%-12.5%. Drug release from DOX-loaded micelles exhibited a biphasic manner in phosphate buffer solution (PBS) at pH 7.4. DOX/GA-GEL could be efficiently accumulated into human liver cancer HepG2 cells. The IC 50 values of DOX/GA-GEL-2 and DOX⋅HCl in HepG2 cells were 0.33 and 0.66 g/mL, respectively. In vivo imaging analysis demonstrated that the fluorescence signals of DiR-labeled GA-GEL-2 micelles were mainly distributed in liver and H22 orthotopic tumor, indicating that GA-GEL had the liver-targeting activity. Compared to DOX⋅HCl, DOX/GA-GEL-2 exhibited better antitumor activity in H22 orthotopic mice. Therefore, these results indicated that GA-GEL could be used as carrier of hydrophobic drug for targeting HCC.

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Fabrication of dual responsive co-delivery system based on three-armed peptides for tumor therapy

Cited by 41 publications

References 41 publications

Tri-stimuli-responsive biodegradable theranostics for mild hyperthermia enhanced chemotherapy

Tri-stimuli-responsive biodegradable theranostics for mild hyperthermia enhanced chemotherapy

Tumor gene therapy by systemic delivery of plasmid DNA with cell-penetrating peptides

Preparation and Evaluation of Doxorubicin-Loaded Micelles Based on Glycyrrhetinic Acid Modified Gelatin Conjugates for Targeting Hepatocellular Carcinoma

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