Construction of CpG Delivery Nanoplatforms by Functionalized MoS₂ Nanosheets for Boosting Antitumor Immunity in Head and Neck Squamous Cell Carcinoma

Abstract

Despite the promising achievements of immune checkpoint blockade (ICB) therapy for tumor treatment, its therapeutic effect against solid tumors is limited due to the suppressed tumor immune microenvironment (TIME). Herein, a series of polyethyleneimine (Mw = 0.8k, PEI0.8k)‐covered MoS2 nanosheets with different sizes and charge densities are synthesized, and the CpG, a toll‐like receptor‐9 agonist, is enveloped to construct nanoplatforms for the treatment of head and neck squamous cell carcinoma (HNSCC). It is proved that functionalized nanosheets with medium size display similar CpG loading capacity regardless of low or high PEI0.8k coverage owing to the flexibility and crimpability of 2D backbone. CpG‐loaded nanosheets with medium size and low charge density (CpG@MM‐PL) could promote the maturation, antigen‐presenting capacity, and proinflammatory cytokines generation of bone marrow‐derived dendritic cells (DCs). Further analysis reveals that CpG@MM‐PL effectively boosts the TIME of HNSCC in vivo including DC maturation and cytotoxic T lymphocyte infiltration. Most importantly, the combination of CpG@MM‐PL and ICB agents anti‐programmed death 1 hugely improves the tumor therapeutic effect, inspiring more attempts for cancer immunotherapy. In addition, this work uncovers a pivotal feature of the 2D sheet‐like materials in nanomedicine development, which should be considered for the design of future nanosheet‐based therapeutic nanoplatforms.

Tackling Severe Neutrophilic Inflammation in Airway Disorders with Functionalized Nanosheets

“…In contrast, the cfDNA-binding capacity of the nanosheets increased progressively for the BP-PGA 5 , BP-PGA 25 , BP-PGA 50 , and BP-PGA 75 nanosheets (Figure F and G), and the presence of fetal bovine serum (FBS) had minimal impact on the cfDNA-binding efficacy of the nanosheets due to the protein resistance properties of polyglycerol. Of note, BP-PGA 50 nanosheets exhibited a higher cfDNA-scavenging capacity than PGA 50 NPs, indicating the importance of the 2D nanoscale geometry for cfDNA scavenger development. , BP-PGA 50 nanosheets effectively scavenged cfDNA while demonstrating mild protein adsorption and low cytotoxicity, highlighting their potential for clinical applications. Collectively, these findings provided evidence that optimization of the hydroxyl:amino ratio at around 50:50 was critical to preparing PGA-based nanoplatforms for cfDNA scavenging.…”

“…Of note, BP-PGA 50 nanosheets exhibited a higher cfDNA-scavenging capacity than PGA 50 NPs, indicating the importance of the 2D nanoscale geometry for cfDNA scavenger development. 30,42 BP-PGA 50 nanosheets effectively scavenged cfDNA while demonstrating mild protein adsorption and low cytotoxicity, highlighting their potential for clinical applications. Collectively, these findings provided evidence that optimization of the hydroxyl:amino ratio at around 50:50 was critical to preparing PGA-based nanoplatforms for cfDNA scavenging.…”

Two-dimensional nanomaterials induced nano-bio interfacial effects and biomedical applications in cancer treatment

“…Hydrophobic, π-π stacking, electrostatic, van der Waals and hydrogen bonding are some of the important non-covalent interactions that enable the loading of antigen. Moreover, the crimpable sheet-like structure and flexible 2D backbone allowed for loading cargos through wrapping and folding [ 142 ]. Such a unique cargo loading of 2D NMs provides a new theoretical basis for the development of antigen carriers.…”