In Vitro and in Vivo mRNA Delivery Using Lipid-Enveloped pH-Responsive Polymer Nanoparticles

Abstract Although single-drug chemotherapy is still an effective treatment for esophageal cancer, its long-term application is limited by severe side effects. Nanomedicines have increasingly attracted attention because of their good biological safety, targeting and high-efficiency loading of multiple drugs. Herein, we have developed a pH-responsive nanocarrier that has high affinity for the transferrin receptor, which is overexpressed by tumor cells. The system is capable of simultaneous delivery of the chemotherapy drug, docetaxel, and the Chinese Medicine, curcumin, for treatment of esophageal cancer. This novel T7-modified targeting nanosystem releases loaded drugs when exposed to the acidic microenvironment of the tumor, and exerts a synergistic anti-tumor effect, and T7-NP-DC with docetaxel and curcumin loading of 10% and 6.1%, respectively. In vitro and in vivo studies showed that improved anti-tumor efficacy could be obtained by loading docetaxel and curcumin into the T7-modified nanocarrierwithout obvious toxicity or side effects, compared to drug without nanocarrier. Furthermore, the nanocarriers conjugated with T7 short peptides were more readily taken up by esophageal cancer cells compared with normal cells.Together, our findings indicate that the materials can safely exert synergistic anti-tumor effects and provide an excellent therapeutic platform for combination therapy of esophageal cancer.

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Evaluation of pH-responsive liposomes containing amino acid-based zwitterionic lipids for improving intracellular drug delivery in vitro and in vivo

Journal of Controlled Release ◽

10.1016/j.jconrel.2009.10.023 ◽

2010 ◽

Vol 142 (2) ◽

pp. 267-276 ◽

Cited By ~ 87

Author(s):

Yosuke Obata ◽

Shoji Tajima ◽

Shinji Takeoka

Keyword(s):

Drug Delivery ◽

Amino Acid ◽

Ph Responsive ◽

Intracellular Drug Delivery ◽

Zwitterionic Lipids

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Mitochondrial Targeted Doxorubicin-Triphenylphosphonium Delivered by Hyaluronic Acid Modified and pH Responsive Nanocarriers to Breast Tumor: in Vitro and in Vivo Studies

Molecular Pharmaceutics ◽

10.1021/acs.molpharmaceut.7b00793 ◽

2018 ◽

Vol 15 (3) ◽

pp. 882-891 ◽

Cited By ~ 23

Author(s):

Hui-Na Liu ◽

Ning-Ning Guo ◽

Tian-Tian Wang ◽

Wang-Wei Guo ◽

Meng-Ting Lin ◽

...

Keyword(s):

Hyaluronic Acid ◽

Breast Tumor ◽

In Vivo Studies ◽

Ph Responsive

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Fluorescent Polymer Nanoparticles for Cell Barcoding In Vitro and In Vivo

Small ◽

10.1002/smll.201701582 ◽

2017 ◽

Vol 13 (38) ◽

pp. 1701582 ◽

Cited By ~ 32

Author(s):

Bohdan Andreiuk ◽

Andreas Reisch ◽

Marion Lindecker ◽

Gautier Follain ◽

Nadine Peyriéras ◽

...

Keyword(s):

Polymer Nanoparticles ◽

Fluorescent Polymer

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Formulation of pH-Responsive Quatsomes from Quaternary Bicephalic Surfactants and Cholesterol for Enhanced Delivery of Vancomycin against Methicillin Resistant Staphylococcus aureus

Pharmaceutics ◽

10.3390/pharmaceutics12111093 ◽

2020 ◽

Vol 12 (11) ◽

pp. 1093

Author(s):

Daniel Hassan ◽

Calvin A. Omolo ◽

Victoria Oluwaseun Fasiku ◽

Ahmed A Elrashedy ◽

Chunderika Mocktar ◽

...

Keyword(s):

Staphylococcus Aureus ◽

High Resolution ◽

Antimicrobial Resistance ◽

Methicillin Resistant Staphylococcus Aureus ◽

Human Beings ◽

Ph Responsive ◽

Methicillin Resistant ◽

13C Nuclear Magnetic Resonance

Globally, human beings continue to be at high risk of infectious diseases caused by methicillin-resistant Staphylococcus aureus (MRSA); and current treatments are being depleted due to antimicrobial resistance. Therefore, the synthesis and formulation of novel materials is essential for combating antimicrobial resistance. The study aimed to synthesize a quaternary bicephalic surfactant (StBAclm) and thereof to formulate pH-responsive vancomycin (VCM)-loaded quatsomes to enhance the activity of the antibiotic against MRSA. The surfactant structure was confirmed using 1H, 13C nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FT-IR), and high-resolution mass spectrometry (HRMS). The quatsomes were prepared using a sonication/dispersion method and were characterized using various in vitro, in vivo, and in silico techniques. The in vitro cell biocompatibility studies of the surfactant and pH-responsive vancomycin-loaded quatsomes (VCM-StBAclm-Qt1) revealed that they are biosafe. The prepared quatsomes had a mean hydrodynamic diameter (MHD), polydispersity index (PDI), and drug encapsulation efficiency (DEE) of 122.9 ± 3.78 nm, 0.169 ± 0.02 mV, and 52.22 ± 8.4%, respectively, with surface charge switching from negative to positive at pH 7.4 and pH 6.0, respectively. High-resolution transmission electron microscopy (HR-TEM) characterization of the quatsomes showed spherical vesicles with MHD similar to the one obtained from the zeta-sizer. The in vitro drug release of VCM from the quatsomes was faster at pH 6.0 compared to pH 7.4. The minimum inhibitory concentration (MIC) of the drug loaded quatsomes against MRSA was 32-fold and 8-fold lower at pH 6.0 and pH 7.4, respectively, compared to bare VCM, demonstrating the pH-responsiveness of the quatsomes and the enhanced activity of VCM at acidic pH. The drug-loaded quatsomes demonstrated higher electrical conductivity and a decrease in protein and deoxyribonucleic acid (DNA) concentrations as compared to the bare drug. This confirmed greater MRSA membrane damage, compared to treatment with bare VCM. The flow cytometry study showed that the drug-loaded quatsomes had a similar bactericidal killing effect on MRSA despite a lower (8-fold) VCM concentration when compared to the bare VCM. Fluorescence microscopy revealed the ability of the drug-loaded quatsomes to eradicate MRSA biofilms. The in vivo studies in a skin infection mice model showed that groups treated with VCM-loaded quatsomes had a 13-fold decrease in MRSA CFUs when compared to the bare VCM treated groups. This study confirmed the potential of pH-responsive VCM-StBAclm quatsomes as an effective delivery system for targeted delivery and for enhancing the activity of antibiotics.

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