One‐Pot, Multicomponent Strategy for Designing Lymphoseek‐Inspired Hetero‐Glycoadjuvant@AuNPs

Abstract

transported to draining lymph nodes. The second approach is based on the activation of antigen-presenting cells (APCs) to induce T cell. [9,10] Recently, inspired by the lymphoseek [11] (which is a mannose-conjugated, dextran-based LN imaging agent, acting as receptor-targeted radiotracer in breast cancer and melanoma patients), we have first developed LN-targeting adjuvant by conjugating toll-like receptor (TLR) [9] agonists, unmethylated Cytosinephosphate-Guanosine (CpG) to natural dextran. [12] Although dextran-functionalized adjuvant could not increase adjuvant internalization, they could distinctly enhance CD8 + T-cell responses, and improve cancer immunotherapy. [12] More importantly, dextran-based adjuvants could not only activate tumor-specific CTL responses, but also inhibit myeloid-derived suppressor cells (MDSCs) in tumor immune microenvironment. [13] Many works indicate that binding between C-type lectin receptors (CLRs) and carbohydrate ligands [14][15][16][17][18][19] is important not only for the induction of T-cell responses, but also for the inhibition of immunosuppressive microenvironment. [13] Therefore, lymphoseek-inspired vaccine should have advantages of promoting vaccine internalization, potentiating CD8 + T-cell responses and reducing the immunosuppressive activity, and become a promising candidate for nextgeneration cancer vaccine.Much effort has been devoted to developing new methodologies for the design and preparation of multifunctional adjuvant, which is the most challenging work. To obtain bioactive adjuvant, simple and highly efficient reaction should be used to formulate adjuvant. To date, most of the works use "grafting to" method to generate target adjuvant. [20][21][22][23] Lynn et al. attached small-molecule TLR-7/8a agonists to hydrophilic polymers to form polymer-TLR-7/8a conjugates by "grafting to" strategy. [24] Recently, inspired by quinone chemistry, we have also introduced "thiol-quinone" reaction to attach thiolated CpG to NPs for fabricating pathogen-mimetic [25][26][27] adjuvants by the "grafting to" method. [28] Besides, few works employ multicomponent strategy to design adjuvants. It is well known that onepot multicomponent strategy offers obvious advantages of simplicity and high efficiency over traditional chemical reactions. Moreover, one-pot strategy is more convenient to obtain high concentration adjuvants. Herein, we report a novel multicomponent strategy to develop lymphoseek-inspired adjuvants in one-pot. First, photo-induced reversible addition-fragmentation Glycoadjuvants Searching for vaccines (antigen and adjuvant) with easy preparation and strong T-cell response are crucial for antitumor immunity. In this work, to design lymphoseek-inspired vaccine possessing the abilities of promoting vaccine internalization and enhancing CD8 + T-cell responses, a simple multicomponent strategy is successfully utilized to fabricate lymph node and dendritic cell dual-targeting glycoadjuvant@AuNPs in one pot, where three different components, catechol-containing glycopol...

Tailor-made glycopolymersviareversible deactivation radical polymerization: design, properties and applications

“…85 Chen and co-workers reported an efficient and green strategy for the synthesis of catechol and sugar-containing polymers via light-induced RAFT polymerization at room temperature. 122–124 In this polymerization process, the RAFT agent itself plays the role of an initiator, chain transfer agent, and termination agent. The catechol groups present in the polymer were exploited for the surface anchoring of gold/silver NPs.…”

“…3,120,156–158 Apart from the “grafting to” method, several authors reported the synthesis of glycopolymer–AuNPs using catechol chemistry without adding any reducing agent. 123,124…”

“…The recognition behavior of glycopolymer decorated gold nanomaterials inspired many researchers for the design of cancer vaccines, vaccine adjuvants, and targeted photothermal therapy (PTT) systems. 123,124,158,159 Some recent articles described the role of glycopolymer–AuNPs in cancer immunotherapy where “pathogen-mimetic” glycoadjuvants are recognized by Toll-like receptors (TLRs) and C-type lectin receptors (CLRs) for the activation of the immune system. 123,124 As a part of the immune system, CD8+ T-cells play crucial roles in suppressing tumours.…”

“…123,124,158,159 Some recent articles described the role of glycopolymer–AuNPs in cancer immunotherapy where “pathogen-mimetic” glycoadjuvants are recognized by Toll-like receptors (TLRs) and C-type lectin receptors (CLRs) for the activation of the immune system. 123,124 As a part of the immune system, CD8+ T-cells play crucial roles in suppressing tumours. CD8+ T cells can kill tumour cells with cytotoxic molecules, such as granzymes and perforin.…”

Green synthesis of gold nanoparticles for immune response regulation: Mechanisms, applications, and perspectives

“…Liu et al 108 conjugated GNPs with mannose and cytosine phosphate guanosine (CpG), which simultaneously activated mannose receptors and TLR9 in innate immune cells. These GNPs promote dendritic cell maturation, thus acting as adjuvants in vaccine development to potentiate the T cell immune response.…”