Back to Search
Start Over
Effective targeted therapy for drug-resistant infection by ICAM-1 antibody-conjugated TPGS modified β-Ga2O3:Cr3+ nanoparticles
- Source :
- Theranostics
- Publication Year :
- 2019
- Publisher :
- Ivyspring International Publisher, 2019.
-
Abstract
- The prevalence of antibiotic resistance and lack of alternative drugs have posed an increasing threat to public health. Here, we prepared β-Ga2O3:Cr3+ nanoparticles modified with ICAM1-antibody-conjugated TPGS (I-TPGS/Ga2O3) as a novel antibiotic carrier for the treatment of drug-resistant infections. Methods: I-TPGS/Ga2O3 were firstly characterized by measuring particle size, morphology, crystal structure, drug loading capacity, and in vitro drug release behaviors. The in vitro antibacterial activities of I-TPGS/Ga2O3/TIG were evaluated using standard and drug-resistant bacteria. The internalization of I-TPGS/Ga2O3 was observed by fluorescence confocal imaging, and the expression levels of the efflux pump genes of TRKP were analyzed by real-time RT-PCR. In vitro cellular uptake and in vivo biodistribution study were performed to investigate the targeting specificity of I-TPGS/Ga2O3 using HUEVC and acute pneumonia mice, respectively. The in vivo anti-infective efficacy and biosafety of I-TPGS/Ga2O3/TIG were finally evaluated using acute pneumonia mice. Results: It was found that TPGS could down-regulate the over-expression of the efflux pump genes, thus decreasing the efflux pump activity of bacteria. I-TPGS/Ga2O3 with small particle size and uniform distribution facilitated their internalization in bacteria, and the TPGS modification resulted in a significant reduction in the efflux of loaded antibiotics. These properties rendered the encapsulated tigecycline to exert a stronger antibacterial activity both in vitro and in vivo. Additionally, targeted delivery of I-TPGS/Ga2O3 mediated by ICAM1 antibodies contributed to a safe and effective therapy. Conclusion: It is of great value to apply I-TPGS/Ga2O3 as a novel and effective antibiotic delivery system for the treatment of drug-resistant infections.
- Subjects :
- Drug
medicine.drug_class
media_common.quotation_subject
Antibiotics
Targeted antibiotic delivery
Medicine (miscellaneous)
Tocopherol polyethylene glycol succinate
Tigecycline
Drug resistance
Pharmacology
β-Ga2O3:Cr3+
Nanocomposites
Mice
In vivo
Drug Resistance, Bacterial
medicine
Animals
Vitamin E
Molecular Targeted Therapy
Internalization
Drug-resistance bacteria
Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
media_common
Drug Carriers
Chemistry
Intercellular Adhesion Molecule-1
Bioimaging
In vitro
Anti-Bacterial Agents
Klebsiella Infections
Disease Models, Animal
Klebsiella pneumoniae
Treatment Outcome
Efflux
Research Paper
medicine.drug
Subjects
Details
- ISSN :
- 18387640
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Theranostics
- Accession number :
- edsair.doi.dedup.....99b91ef3ea8b0e5bbcffc72cc427cc57