Self-Assembled pH-Sensitive Nanoparticles Based on Ganoderma lucidum Polysaccharide–Methotrexate Conjugates for the Co-delivery of Anti-tumor Drugs

In tumor therapy, polymer nanoparticles are ideal drug delivery materials because they can mask the disadvantages of anti-tumor drugs such as poor solubility in water, high toxicity, and side effects. However, most polymer-based nanoparticles do not themselves have anti-tumor properties. Herein, a novel pH-sensitive nanoparticle drug delivery system based on Ganoderma lucidum polysaccharides (GLPs), which have demonstrated anti-tumor activities, was designed to enable the delivery of methotrexate (MTX) and 10-hydroxycamptothecin (HCPT) to tumor cells, where they could exert synergistic anti-tumor effects. The prepared nanoparticles were irregularly spherical in shape with a uniform particle size of ∼190 nm, and they exhibited a high drug-loading capacity (MTX 21.5% and HCPT 22.6%) and excellent biocompatibility. Moreover, the loaded MTX and HCPT units were rapidly released under acidic conditions within the tumor cells while remaining stable under normal physiological conditions. Meanwhile, compared to free MTX and HCPT, the GLP-APBA-MTX/HCPT nanoparticles presented exhibited better tumor suppressive effects and fewer side effects in vivo, which indicates that they may be an effective anti-tumor treatment strategy.