Polarization of tumor associated macrophages (TAMs) has been a promising therapeutic paradigm for tumor. However, how to achieve precise regulation of TAMs and high efficiency of tumor immunotherapy is still a huge challenge. Here, we report dicarboxy fullerene modified with mannose (DCFM) as an immunomodulator to selectively polarize TAMs and prominently boost anti-tumor immunity. The dicarboxy fullerene molecule was synthesized through the Prato reaction and further covalently bonded with mannose, obtaining the DCFM with well-defined structure. Due to the exist of mannose in DCFM, it could accurately recognize mannose receptor in TAMs. Our cellular experiment results showed that mannose modification could notably promote the uptake of DCFM by the immunosuppressive M2-type macrophages that effectively reprogrammed M2-type macrophages into anti-tumor M1-type macrophages, leading to enhance the phagocytosis of tumor cells by macrophages and inhibiting tumor cells migration. Subsequently, we observed that DCFM could significantly distribute into tumor tissues by in vivo fluorescence imaging. Importantly, DCFM exhibited a superior anti-tumor efficiency in the subcutaneous colorectal tumor model. In addition, it showed that DCFM precisely polarized TAMs into M1-type macrophages and actively increased the infiltration of cytotoxic T lymphocytes (CTLs), inducing profound tumor growth inhibition.

Fullerenes and metallofullerenes have unique structure and novel electronic characteristics, which have great application potential in biomedicine, quantum and information fields. However, how to increase the yields of metallofullerenes is a key technical problem that must be solved for practical application. In order to synthesize metallofullerenes with high yields and selectivity, it is necessary to understand the formation mechanism and develop new synthesis methods. Our research focuses on the comprehensive analysis of the formation mechanism of fullerenes and metallofullerenes in order to find a way to break through the bottleneck of their productivity. On the one hand, the formation process of fullerenes was simulated by density functional theory and molecular dynamics, which directed the optimization of the synthesis conditions of fullerenes. On the other hand, a series of metallofullerenes with specific structures and functions were prepared by accurately controlling the inert gas pressure, arc gas composition and raw material composition of metallofullerenes, and the efficient preparation strategy of metallofullerenes was developed. Finally, we also explored the protection methods after the formation of metallofullerenes, and achieved certain results, laying a solid foundation for the industrialization of metallofullerenes in the future.

Functional fullerene derivatives exhibit special inhibitory effects on tumor progress and metastasis via diverse tumor microenvironment regulations, while the elusive molecular mechanisms hinder their clinical transformation. Herein, it is initially revealed that nanosize aminated fullerene (C₇₀-EDA) can activate autophagic flux, induce G0/G1 cell cycle arrest to abrogate cancer cell proliferation, and significantly inhibit tumor growth in vivo. Mechanismly, C₇₀-EDA promotes the expression of cathepsin D involved in autophagic activation via post-transcriptional regulation, attributing to the interaction with a panel of RNA binding proteins. The accumulation of cathepsin D induces the autophagic degradation of cyclin D1, which arouses G0/G1 phase arrest. This work unveils the fantastic anti-tumor activity of aminated fullerene, elucidates the molecular mechanism, and provides a new strategy for the antineoplastic drug development on functional fullerenes.

Magneto-luminescent molecules have significant applications in data storage and quantum computing. However, design of these bi-functional molecules coupled with magnetic behavior and photoluminescence is still challenging. In this work, we report a metallofullerene DyErScN@Ⅰ_h-C₈₀ exhibiting single-molecule magnet (SMM) behavior and near-infrared emission. For DyErScN@Ⅰ_h-C₈₀, two functional lanthanide metal ions of Dy³⁺ (SMM function) and Er³⁺ (luminescent function) are integrated inside a fullerene cage using a trimetallic nitride template, and its structure has been unambiguously characterized by single-crystal X-ray diffraction. Magnetic measurements revealed that DyErScN@Ⅰ_h-C₈₀ behaves as a SMM with a blocking temperature up to 9 K resulting from the intramolecular magnetic interaction between Dy³⁺ and Er³⁺ ions. Moreover, DyErScN@Ⅰ_h-C₈₀ exhibits temperature-dependent near-infrared emission around 1.5 µm with multiple splitting peaks from Er³⁺, which arises from the influence of Dy³⁺ ion. This study provides a new strategy to synthesize new magneto-luminescent molecule materials.