posted on 2021-12-09, 13:03authored byFeihu Bi, Jin Zhang, Zengming Wei, Deshui Yu, Shuai Zheng, Jie Wang, Hongyu Li, Zan Hua, Hui Zhang, Guang Yang
A library
of 14 dynamic glycopeptide amphiphilic dendrimers composed
of 14 hydrophilic and bioactive saccharides (seven kinds) as dendrons
and 7 hydrophobic peptides (di- and tetrapeptides) as arms with β-cyclodextrin
(CD) as a core were facially designed and synthesized in several steps.
Fourteen saccharides were first conjugated to the C-2 and C-3 positions
of CD, forming glycodendrons. Subsequently, seven oligopeptide arms
were introduced at the C-6 positions of a CD moiety by an acylhydrazone
dynamic covalent bond, resulting in unique Janus amphiphilic glycopeptide
dendrimers with precise and varied molecular structures. The kinds
of hydrophilic parts of saccharides and hydrophobic parts of peptides
were easily varied to prepare a series of amphiphilic Janus glycopeptide
dendrimers. Intriguingly, these obtained amphiphilic glycopeptide
dendrimers showcased very different self-assembly behaviors from the
traditional amphiphilic linear block-copolymers and self-assembled
into different glyco-nanostructures with controllable morphologies
including glycospheres, worm-like micelles, and fibers depending upon
the repeat unit ratio of saccharides and phenylalanine. Both glycodendrons
and glycopeptide assemblies displayed strong and specific recognitions
with C-type mannose-specific lectin. Moreover, these glycopeptide
nanomaterials can encapsulate exemplary hydrophobic molecules such
as Nile red (NR). The dye-loaded glycopeptide nanostructures showed
a pH-controllable release behavior around the physiological and acidic
tumor environment. Furthermore, cell experiments demonstrated that
such glyco-nanostructures can further facilitate the functions of
a model drug of the pyridone agent to reduce the expression of monocyte
chemotactic protein-1 (MCP-1) and interleukin -1beta (IL-1β)
in the primary peritoneal macrophages via encapsulating drugs. Considering
all the abovementioned advantages including unique and precise structures,
bioactivity, targeting, and controllable cargo release, we believe
that these findings can not only enrich the library of glycopeptides
but also provide a new avenue to the fabrication of smart and structure-controllable
glyco-nanomaterials which hold great potential biological applications
such as targeted delivery and release of therapeutic and bioactive
molecules.