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

AGAZZI, MAXIMILIANO L.; HERRERA, SANTIAGO E.; CORTEZ, M. LORENA; MARMISOLLÉ, WALDEMAR; AZZARONI, OMAR

Vancouver

Simposio; Vancouver Nanomedicine Day 2020; 2020

The University of British Columbia

Nanocarriers with a size of approximately 100-200 nm show good tumor accumulation but havelimited tissue penetration capability. In contrast a size smaller than 10 nm is capable of deeptumor penetration but will be quickly cleared by the systemic circulation. To surmount this dilemma, multistage delivery systems with size reduction capacity have been proposed.Here we developed a simple and fast supramolecular approach to construct size-shrinkablepolyamine-salt aggregates by ionic cross-linking of biodegradable poly-L-lysine dendrigraft withtripolyphosphate 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.