Biocompatible single-chain polymer nanoparticles loaded with an antigen mimetic as potential anticancer vaccine

Abstract

The “pancarcinoma” Tn antigen (αGalNAc-O-Ser/Thr) is a tumor-associated carbohydrate antigen (TACA) overexpressed on the surface of cancer cells and suitable target for anticancer vaccines. However, TACAs commonly show weak immunogenicity, low in vivo stability, and poor bioavailability. To address these issues, the development of physiologically stable TACA synthetic mimetics and novel nanocarriers for multivalent display are object of intense research. Nanomaterials represent suitable scaffolds to multimerize antigens, but absence of toxicity, easy functionalization and capability to incorporate biomolecules are compulsory characteristics for vaccine nanocarriers. Here, we report on the conjugation of a synthetic Tn-antigen mimetic to biocompatible and water-dispersible dextran-based single-chain nanoparticles (DXT-SCPNs). In vitro stimulation of PBMCs and analysis of interleukins production indicated a specific innate immune modulation mediated by the multivalent presentation of the Tn mimetic at the nanoparticle surface. These preliminary results pave the way for the development of Tn-mimetic clusters on biocompatible DXT-SCPN for TACA-based vaccines.

The B & B approach: Ball-milling conjugation of dextran with phenylboronic acid (PBA)-functionalized BODIPY

“…Furthermore, the presence of hydroxy groups allows for an easy chemical functionalization with complementary functional groups. Indeed, dextrans and their derivatives have been widely used in biomedical applications, especially as drug and gene carriers, both in hydrogels and in nanoparticulate formulations [ 29 – 32 ]. In this regard, the incorporation of hydrophobic moieties in the branched structure of dextrans induces self-assembly into nanoparticles, depending on the degree of substitution.…”

Nucleic acids presenting polymer nanomaterials as vaccine adjuvants

“…128,129 Nativi and co-workers incorporated the a-Tn antigen mimetic moiety to dextran SCNPs to trigger immune responses similar to immune proteins on human peripheral blood mononuclear cells (PBMCs). 130 Since the native antigen has limitations in terms of stability and antibody response, presentation on a SCNP was hypothesized to enhance the immune active potential. Indeed, upregulation of IL-6 and IL-10 was measured, which was absent in nonfunctionalized SCNPs.…”

Spontaneous Self-Assembly of Single-Chain Amphiphilic Polymeric Nanoparticles in Water

“…Water-soluble SCPNs have attracted significant attention in recent years due to their potential applications in various fields, such as catalysis [ 23 , 24 , 25 ], drug delivery [ 26 , 27 , 28 ] and bioimaging [ 29 , 30 , 31 ]. Current strategies for the synthesis of water-soluble SCPNs are mainly based on noncovalent interactions (intramolecular hydrogen bonds and metal-ligand interactions) [ 15 , 23 , 32 , 33 , 34 , 35 ] and photochemical reactions [ 9 , 21 , 36 ] in aqueous solution.…”