Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
Add more filters










Database
Language
Publication year range
1.
ACS Nano ; 17(7): 6292-6316, 2023 04 11.
Article in English | MEDLINE | ID: mdl-36951612

ABSTRACT

Bacterial drug resistance is becoming increasingly serious, and it is urgent to develop effective antibacterial drugs. Antimicrobial peptides (AMPs), as potential candidates against bacteria, have a broad prospect for development. Herein, a series of AMPs with biological characteristics (net positive charge, amphiphilicity, and α-helix), an AXA motif recognized by membrane bound serine protease type I signal peptidases (SPase I), an FLPII motif to reduce hemolysis, and a monosaccharide motif to improve the stability and activity were designed and synthesized, and among which, the glycolipidpeptide GLP6 (glycosylated LP6 lipopeptide) had excellent antibacterial and immunomodulatory activity, good stability and biocompatibility, and excellent biofilm eradication and membrane penetrating activity. The positively charged spherical aggregates formed by self-assembly of GLP6 could encapsulate tetracycline (TC) to form GLP6@TC with a sustained-release effect, which could enhance the sensitivity of bacteria to the antibiotic and realize combined sterilization. The results of acute peritonitis and bacterial keratitis showed that GLP6@TC had a good combined antibacterial effect and the ability to inhibit interleukin-2 (IL-2), which could significantly reduce the inflammatory response while treating bacterial infection, and it had great potential for application. The results of computer molecular docking showed the AXA motif could effectively bind to SPase I, which was consistent with the results of biological experiments. In general, the study could provide a perspective for the design of AMPs and combined antibacterial therapy.


Subject(s)
Anti-Infective Agents , Antimicrobial Cationic Peptides , Molecular Docking Simulation , Antimicrobial Cationic Peptides/chemistry , Anti-Infective Agents/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Bacteria , Microbial Sensitivity Tests
2.
Colloids Surf B Biointerfaces ; 223: 113186, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36746066

ABSTRACT

Herein, an amphiphilic cationic anticancer lipopeptide P17 with α-helical structure was synthesized based on the integration of KLA and RGD peptide which could bind with the receptor of integrin αvß3. P17 could self assemble into stable spherical aggregates in aqueous solution, and which could encapsulate the anticancer drugs (Such as Dox) to form P17 @ Anticancer drug nanomedicine (P17 @ Dox nanomedicine) which could play the combined therapy of P17 and anticancer drugs (Dox). The encapsulation efficiency of P17 aggregates to Dox was 80.4 ± 3.2 %, and the release behavior of P17 @ Dox nanomedicine in vitro had the characteristics of slow-release and pH responsiveness. The experiments in vitro showed that P17 lipopeptide had low cytotoxicity, high serum stability, low hemolysis and strong penetrating membrane ability. The release of Dox from P17 @ Dox in cells was time-dependment, and the P17 @ Dox nanomedicine had a good anticancer effect. The experiments in vivo showed that P17 and P17 @ Dox nanomedicine both had low hemolysis, and P17 @ Dox nanomedicine could effectively inhibit tumor growth and significantly reduce the toxic and side effects of Dox. Molecular docking experiments showed that P17 could effectively interact with the receptor of integrin αvß3. In conclusion, P17 lipopeptide could be used as an excellent drug carrier and play the combined anticancer effect of P17 and anticancer drugs.


Subject(s)
Antineoplastic Agents , Nanoparticles , Humans , Doxorubicin/chemistry , Lipopeptides , Hemolysis , Molecular Docking Simulation , Nanoparticles/chemistry , Antineoplastic Agents/pharmacology , Oligopeptides/chemistry , Drug Carriers/chemistry , Integrins , Hydrogen-Ion Concentration , Cell Line, Tumor
3.
Biomater Sci ; 10(7): 1724-1741, 2022 Mar 29.
Article in English | MEDLINE | ID: mdl-35253807

ABSTRACT

Herein, an amphiphilic cationic α-helical anticancer lipopeptide, P10 with low toxicity and high penetrating membrane activity was developed. This lipopeptide could self-assemble into stable spherical aggregates in aqueous solution and encapsulate Dox with a hydrophobic structure to form the P10@Dox nanomedicine. The Dox encapsulation efficiency was 81.3% ± 3.48% and its release from the P10@Dox nanomedicine had the characteristics of slow release and pH response. The in vitro experiments showed that the P10 lipopeptide had low toxicity, excellent membrane penetrating activity and high serum stability, the release of Dox from P10@Dox in cells was time and concentration dependent, and the P10@Dox nanomedicine played a good anti-cancer role. The animal experiments and tissue sections showed that the P10 lipopeptide and P10@Dox nanomedicine both had low hemolysis, and P10@Dox nanomedicine not only greatly reduced the toxicity and side effects of Dox, but also effectively inhibited the tumor growth. Additionally, it was surprising that P10 exhibited certain analgesic activity, which could reduce the accompanying cancer pain, while playing an effective role in cancer therapy. Thus, the results showed that the P10 lipopeptide can be used as an ideal drug carrier and it has great application potential in the field of clinical cancer therapy.


Subject(s)
Doxorubicin , Nanoparticles , Analgesics/pharmacology , Animals , Doxorubicin/chemistry , Doxorubicin/pharmacology , Hemolysis , Hydrogen-Ion Concentration , Nanoparticles/chemistry , Peptides/chemistry , Peptides/pharmacology
4.
J Mater Chem B ; 10(11): 1858-1874, 2022 03 16.
Article in English | MEDLINE | ID: mdl-35229088

ABSTRACT

The development of new antimicrobial drugs is urgently required to overcome bacterial resistance which is a serious threat to human health. Antimicrobial peptides (AMPs) which are ideal substitutes for traditional antibiotics have a unique mechanism of action and do not easily cause bacterial resistance. Herein, a series of new AMPs were designed and synthesized based on the biological characteristics of natural AMPs (such as the positive charge, α-helical structure and amphiphilicity). Biological screening of the AMPs provided an antimicrobial lipopeptide LP21 with efficient antimicrobial activity, serum stability, low cytotoxicity and high membrane-disruptive activity. Besides, LP21 could self-assemble into spherical aggregates in aqueous solutions which encapsulated TC to form LP21@TC nanomedicine, and the encapsulation efficiency was about 50.03 ± 3.03%. More impressively, both LP21 and LP21@TC nanomedicine displayed significant therapeutic effects in vivo, and the LP21@TC nanomedicine could exert a synergistic antimicrobial effect. This work is expected to provide a new research vision for the design of AMPs and synergistic antibacterial sensitization treatment.


Subject(s)
Anti-Infective Agents , Bacterial Infections , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/chemistry , Antimicrobial Peptides , Humans , Lipopeptides
SELECTION OF CITATIONS
SEARCH DETAIL
...