The activity of polysaccharides is usually related to molecular weight. The molecular weight of polysaccharides is critical to their immunological effect in cancer therapy. Herein, the Codonopsis polysaccharides of different molecular weights were isolated using ultrafiltration membranes of 60- and 100-wDa molecular weight cut-off to determine the relationship between molecular weight and antitumor activities. First, three water-soluble polysaccharides CPPS-I (<60 wDa), CPPS-II (60–100 wDa), and CPPS-III (>100 wDa) from Codonopsis were isolated and purified using a combination of macroporous adsorption resin chromatography and ultrafiltration. Their structural characteristics were determined through chemical derivatization, GPC, HPLC, FT–IR, and NMR techniques. In vitro experiments indicated that all Codonopsis polysaccharides exhibited significant antitumor activities, with the tumor inhibition rate in the following order: CPPS-II > CPPS-I > CPPS-III. The treatment of CPPS-II exhibited the highest inhibition rate at a high concentration among all groups, which was almost as efficient as that of the DOX·HCL (10 μg/mL) group at 125 μg/mL concentration. Notably, CPPS-II demonstrated the ability to enhance NO secretion and the antitumor ability of macrophages relative to the other two groups of polysaccharides. Finally, in vivo experiments revealed that CPPS-II increased the M1/M2 ratio in immune system regulation and that the tumor inhibition effect of CPPS-II + DOX was superior to that of DOX monotherapy, implying that CPPS-II + DOX played a synergistic role in regulating the immune system function and the direct tumor-killing ability of DOX. Therefore, CPPS-II is expected to be applied as an effective cancer treatment or adjuvant therapy.

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Isolation, Purification, and Structural Characterization of Polysaccharides from Codonopsis pilosula and Their Anti-Tumor Bioactivity by Immunomodulation

Recent advances in the field of drug delivery have opened new avenues for the development of novel nanodrug delivery systems (NDDS) in cancer therapy. Self-assembled nanoparticles (SANPs) based on tumor microenvironment have great advantages in improving antitumor effect, and pH-responsive SANPs prepared by the combination of pH-responsive nanomaterials and self-assembly technology can effectively improve the efficacy and reduce the systemic toxicity of antitumor drugs. In this review, we describe the characteristics of self-assembly and its driving force, the mechanism of pH-responsive NDDS, and the nanomaterials for pH-responsive SANPs type. A series of pH-responsive SANPs for tumor-targeted drug delivery are discussed, with an emphasis on the relation between structural features and theranostic performance.

pH-Responsive Self-Assembled Nanoparticles for Tumor-Targeted Drug Delivery.

Targeting tumor-associated macrophages (TAMs) has emerged as a promising approach in cancer therapy. This article provides a comprehensive review of recent advancements in the field of nanomedicines targeting TAMs. According to the crucial role of TAMs in tumor progression, strategies to inhibit macrophage recruitment, suppress TAM survival, and transform TAM phenotypes are discussed as potential therapeutic avenues. To enhance the targeting capacity of nanomedicines, various approaches such as the use of ligands, immunoglobulins, and short peptides are explored. The utilization of live programmed macrophages, macrophage cell membrane-coated nanoparticles and macrophage-derived extracellular vesicles as drug delivery platforms is also highlighted, offering improved biocompatibility and prolonged circulation time. However, challenges remain in achieving precise targeting and controlled drug release. The heterogeneity of TAMs and the variability of surface markers pose hurdles in achieving specific recognition. Furthermore, the safety and clinical applicability of these nanomedicines requires further investigation. In conclusion, nanomedicines targeting TAMs hold great promise in cancer therapy, offering enhanced specificity and reduced side effects. Addressing the existing limitations and expanding our understanding of TAM biology will pave the way for the successful translation of these nano-therapies into clinical practice.

Tumor-associated macrophages in nanomaterial-based anti-tumor therapy: as target spots or delivery platforms

The immune functions of the body are intricately intertwined with the onset and advancement of tumors, and immunotherapy mediated by bioactive compounds has exhibited initial effectiveness in overcoming chemotherapy resistance and inhibiting tumor growth. However, the comprehensive interpretation of the roles played by immunologic components in the process of combating tumors remains to be elucidated. In this study, the Codonopsis pilosula glucofructan (CPG) prepared in our previous research was employed as an immunopotentiator, and the impacts of CPG on both the humoral and cellular immunity of S180 tumor-bearing mice were investigated. Results showed that CPG administration of 100 mg/kg could effectively inhibit tumor growth in mice with an inhibitory ratio of 45.37% and significantly improve the expression of Interleukin-2 (IL-2), Interferon-γ (IFN-γ), and Tumor Necrosis Factor-α (TNF-α). Additionally, CPG clearly enhanced B-cell-mediated humoral immunity and immune-cell-mediated cellular immunity, and, finally, induced S180 cell apoptosis by arresting cells in the G0/G1 phase, which might result from the IL-17 signaling pathway. These data may help to improve comprehension surrounding the roles of humoral and cellular immunity in anti-tumor immune responses.

Systemic Immunomodulatory Effects of Codonopsis pilosula Glucofructan on S180 Solid-Tumor-Bearing Mice

In recent years, Flammulina velutipes (F. velutipes) has attracted consequential attention in various research fields due to its rich composition of proteins, vitamins, amino acids, polysaccharides, and polyphenols. F. velutipes polysaccharides (FVPs) are considered as key bioactive components of F. velutipes, demonstrating multiple physiological activities, including immunomodulatory, anti-inflammatory, and antibacterial properties. Moreover, they offer health benefits such as antioxidant and anti-aging properties, which have exceptionally valuable clinical applications. Polysaccharides derived from different sources exhibit a wide range of biomedical functions and distinct biological activities. The varied biological functions of polysaccharides, coupled with their extensive application in functional foods and clinical applications, have prompted a heightened focus on polysaccharide research. Additionally, the extraction, deproteinization, and purification of FVPs are fundamental to investigate the structure and biological activities of polysaccharides. Therefore, this review provides a comprehensive and systematic overview of the extraction, deproteinization, purification, characterization, and structural elucidation of FVPs. Furthermore, the biological activities and mechanisms of FVPs have been further explored through in vivo and in vitro experiments. This review aims to provide a theoretical foundation and guide future research and development of FVPs. 

Research progress and future development potential of Flammulina velutipes polysaccharides in the preparation process, structure analysis, biology, and pharmacology: A review.

Rhodiola rosea polysaccharides-based nanoparticles loaded with DOX boosts chemo-immunotherapy for triple-negative breast cancer by re-educating tumor-associated macrophages.

Self-adjuvant Astragalus polysaccharide-based nanovaccines for enhanced tumor immunotherapy: a novel delivery system candidate for tumor vaccines.

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Rhodiola rosea polysaccharides-based nanoparticles loaded with DOX boosts chemo-immunotherapy for triple-negative breast cancer by re-educating tumor-associated macrophages.

Isolation, Purification, and Structural Characterization of Polysaccharides from Codonopsis pilosula and Their Anti-Tumor Bioactivity by Immunomodulation

Self-adjuvant Astragalus polysaccharide-based nanovaccines for enhanced tumor immunotherapy: a novel delivery system candidate for tumor vaccines.