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Senescence Reprogramming by TIMP1 Deficiency Promotes Prostate Cancer Metastasis

Ilaria Guccini,
 Ajinkya Revandkar,
 Mariantonietta D'Ambrosio,
Manuel Colucci,
Emiliano Pasquini,
Simone Mosole,
Martina Troiani,
Daniela Brina,
Raheleh Sheibani-Tezerji,
Angela Rita Elia,
Andrea Rinaldi,
Nicolò Pernigoni,
Jan Hendrik Rüschoff,
Susanne Dettwiler,
Angelo M. De Marzo,
Emmanuel S. Antonarakis,
Costanza Borrelli,
Andreas E. Moor,
Ramon Garcia-Escudero,
Abdullah Alajati,
Giuseppe Attanasio,
Marco Losa,
Holger Moch,
Peter Wild,
Gerda Egger,
Andrea Alimonti

Cancer Cell


Infectious diseases induced by multidrug-resistant bacteria are a challenging problem in medicine because of global rise in the drug resistance to pathogenic bacteria.

Despite great efforts on the development of antibiotics and antimicrobial agents, there is still a great need to develop a strategy to early detect bacterial infections and eradicate bacteria effectively and simultaneously. The innate immune systems of various organisms produce antimicrobial peptides, which kill a broad range of bacteria with minimal cytotoxicity to mammalian cells.

Therefore, antimicrobial peptides have recently attracted increasing attention as an alternative to conventional antibiotics in antibacterial medications.

Here, we report a new family of antibacterial agents, which is formulated from self-assembly of a chimeric antimicrobial lipopeptide (DSPE-HnMc) and amphiphilic biodegradable polymers. HnMc micelles could effectively bind the bacterial membrane to kill a wide spectrum of bacteria and bacterial biofilms.

In the studies of mouse models of drug-resistant bacterial infections, HnMc micelles could target bacterial infections with high specificity and also kill drug-resistant bacteria effectively, demonstrating the great potential of HnMc micelles as imaging and targeted antibacterial agents.

These findings also provide new insight into the design of antimicrobial peptide-based nanomedicine for detection and treatment of bacterial infections.


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