Self-assembled peptide dendrigraft supraparticles with potential application in pH/enzyme-triggered multistage drug release

• Published in: Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2020-06, Vol.190, p.110895, Article 110895
• Main Authors: Agazzi, Maximiliano L., Herrera, Santiago E., Cortez, M. Lorena, Marmisollé, Waldemar A., Azzaroni, Omar
• Format: Article
• Language: English
• Subjects: Curcumin - chemistry; Curcumin - metabolism; Dendrimers - chemical synthesis; Dendrimers - chemistry; Dendrimers - metabolism; Doxorubicin - chemistry; Doxorubicin - metabolism; Drug Delivery Systems; Drug Liberation; Hydrogen-Ion Concentration; Macromolecular Substances - chemistry; Macromolecular Substances - metabolism; Molecular Structure; Multistage drug release; Particle Size; Peptides - chemical synthesis; Peptides - chemistry; Peptides - metabolism; Poly-L-lysine dendrigraft; Polyamine-salt aggregates; Polyamines - chemistry; Polyamines - metabolism; Polylysine - chemistry; Polylysine - metabolism; Size pH-switchable supraparticles; Surface Properties; Trypsin - chemistry; Trypsin - metabolism; Trypsin-triggered release
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2020.110895

[Display omitted] •Ionic crosslinking of biodegradable peptide dendrimers can lead to well-defined polymeric supraparticles.•pH-sensitive size-switchable dendrimer-based supraparticles show a remarkable capacity to encapsulate different molecules.•After pH-triggered disassembly, the cargo trapped in dendrimers can be released by action of trypsin enzyme.•Dendrimer supraparticles are promising multistage nanocarriers with remarkable properties for drug delivery applications. Multistage delivery systems with size reduction capacity have been proposed as a powerful strategy for improving tissue drug penetration. Here we developed a simple and fast supramolecular approach to construct size-shrinkable polyamine-salt aggregates by ionic cross-linking of biodegradable poly-L-lysine dendrigraft with tripolyphosphate anion. The use of a peptide dendrimer as a nanobuilding block (∼7 nm in diameter) allows the formation of supraparticles (SPs) with well-defined dimensions (∼200 nm in diameter), narrow size distribution and great capacity to encapsulate different molecules, including chemotherapeutic agents as Curcumin and Doxorubicin. When exposed to slightly acidic environments, the crosslinked matrix is instantaneously disassembled to free dendrimer units. Subsequently, model cargo molecules entrapped in the dendrimer architecture can be released by the action of trypsin enzyme through peptide biodegradation. Therefore, these SPs with proved sequential pH and enzyme-responsiveness could be exploited as nanocarriers in multistage drug delivery systems.