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'In vivo self-assembled' nanoprobes for optimizing autophagy-mediated chemotherapy
- Source :
- Biomaterials. 141
- Publication Year :
- 2017
-
Abstract
- Autophagic therapy is regarded as a promising strategy for disease treatment. Appropriate autophagy regulations in vivo play a crucial role in translating this new concept from benchside to bedside. So far, emerging technologies are required to spatially and quantitatively monitor autophagic process in vivo in order to minimize the cytotoxity concerns associated with autophagy-mediated therapy. We successfully demonstrate the "proof-of-concept" study on autophagy-mediated chemotherapy in mice. Here, we describe a photoacoustic (PA) nanoprobe based on "in vivo self-assembly" idea for real-time and quantitative detection of autophagy in mice for the first time. The purpurin-18 (P18) monomer is connected to hydrophilic poly(amidoamine) dendrimer (4th generation) through a peptide (GKGSFGFTG) that can be cleaved by an autophagy-specific enzyme, i.e., ATG4B, consequently resulting in aggregation of P18 and enhanced PA signals. Based on this aggregation-induced "turn-on" PA signals, we noninvasively determine the ATG4B activity for monitoring autophagy of tumor in vivo. According to the results of PA imaging, we could optimize chemotherapy efficacy through precisely modulating autophagy, which thereby decrease systemic toxicity from chemotherapeutics and autophagy inhibitors. We envision it will pave the way for developing autophagy-based treatment of diseases in the future.
- Subjects :
- 0301 basic medicine
Porphyrins
medicine.medical_treatment
Biophysics
Nanoprobe
Photoacoustic imaging in biomedicine
Autophagy-Related Proteins
Bioengineering
Antineoplastic Agents
Biology
Self assembled
Biomaterials
Photoacoustic Techniques
03 medical and health sciences
Mice
In vivo
Neoplasms
medicine
Autophagy
Polyamines
Animals
Humans
Disease treatment
Chemotherapy
Mice, Inbred BALB C
Cell biology
Cysteine Endopeptidases
030104 developmental biology
Systemic toxicity
Mechanics of Materials
Immunology
Ceramics and Composites
MCF-7 Cells
Female
Subjects
Details
- ISSN :
- 18785905
- Volume :
- 141
- Database :
- OpenAIRE
- Journal :
- Biomaterials
- Accession number :
- edsair.doi.dedup.....281878fbd11ebebd40f48619babae793