Tailored Multivalent Targeting of Siglecs with Photosensitizing Liposome Nanocarriers

Abstract

The modification of surfaces with multiple ligands allows the formation of platforms for the study of multivalency in diverse processes. Herein we use this approach for the implementation of a photosensitizer (PS)-nanocarrier system that binds efficiently to siglec-10, a member of the CD33 family of siglecs (sialic acid (SA)-binding immunoglobulin-like lectins). In particular, a zinc phthalocyanine derivative bearing three SA moieties (PcSA) has been incorporated in the membrane of small unilamellar vesicles (SUVs), retaining its photophysical properties upon insertion into the SUV's membrane. The interaction of these biohybrid systems with human siglec-10-displaying supported lipid bilayers (SLBs) has shown the occurrence of weakly multivalent, superselective interactions between vesicle and SLB. The SLB therefore acts as an excellent cell membrane mimic, while the binding with PS-loaded SUVs shows the potential for targeting siglec-expressing cells with photosensitizing nanocarriers.

Multivalent glycosystems for human lectins

“…Recently, trivalent sialic acid glycodendrons functionalised in the focal position with different molecules such as phthalocyanine as a photosensitiser or tetraphenylethene as an aggregation-induced emission (AIE)-active fluorophore have been used to target different Siglec subtypes. 310,311…”

“…Regarding the first one, Almeida-Marrero et al 310 have employed a sialic acid glycodendron zinc phthalocyanine derivative, incorporated into the membrane of small unilamellar vesicles, as multivalent ligand for targeting Siglec-10-displaying supported lipid bilayers as proof of concept (Fig. 13).…”

Engineering Nanoenzymes Integrating Iron-based MOFs with Pt NPs for Enhanced PDT-Ferroptosis Therapy

“…With the development of nanotechnology, numerous drug delivery carriers have been explored to deliver PSs, such as liposomes [4], polymeric micelles [5], inorganic nanoparticles[6], and so on. However, most nanocarriers show shortcomings such as poor drug loading [7], poor physical stability [8], and nonrepeatability.…”

Programming DNA Aptamer Arrays of Prescribed Spatial Features with Enhanced Bioavailability and Cell Growth Modulation

“…There are a variety of scaffold materials that have been used to assemble multivalent ligand systems including polymers, , nanoparticles, , peptides, , vesicles, , and DNA and RNA structures, − among which DNA nanotechnology has demonstrated unparallel ligand-assembling capability with unprecedented precision, accuracy, and versatility for studying ligand–receptor interactions. − Herein, we aim to construct a nanoscale multivalent EpCAM aptamer array by using DNA scaffolds to enhance its targeting capability to EpCAM clusters on the cell surface toward better performances both in vitro and in vivo . Specifically, we constructed a nanoscale rectangular DNA pegboard with a number of 12 docking sites for the assembly of EpCAM aptamer (SYL3C) arrays.…”

“…6,7 The well-delineated patch-like clustering nature of EpCAM on the cell membrane inspires us that designing scaffold-templated multivalent ligand systems against EpCAM clusters may significantly boost its targeting capability to benefit its applications in cancer diagnosis and therapy. 8 There are a variety of scaffold materials that have been used to assemble multivalent ligand systems including polymers, 9,10 nanoparticles, 11,12 peptides, 13,14 vesicles, 15,16 and DNA and RNA structures, 17−23 among which DNA nanotechnology has demonstrated unparallel ligand-assembling capability with unprecedented precision, accuracy, and versatility for studying ligand−receptor interactions. 24−30 Herein, we aim to construct a nanoscale multivalent EpCAM aptamer array by using DNA scaffolds to enhance its targeting capability to EpCAM clusters on the cell surface toward better performances both in vitro and in vivo.…”