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

Abstract

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.

Design, fabrication and evaluation of amphiphilic hyaluronic acid conjugates as efficient carriers of 6‐thioguanine for in vitro anticancer drug delivery applications

“…TG, into the system which resisted further proliferation of the cancer cells hence resulted in lower IC 50 with increasing time. 65 Similarly, the results for HeLa cells showed an efficient anticancer effect of HD-2(TG) nanoparticles where IC 50 values were similar to those for HepG2 cells. Comparative analysis of HD-2(TG) and HD-2 on HeLa and HepG2 cells showed a greater degree of anticancer effect against HepG2 cells as compared with HeLa cells, which might be attributed to higher expression of CD44 receptors on HepG2 cells, as reported in the literature.…”

“…This could be due to sustained release of the entrapped drug, i.e. TG, into the system which resisted further proliferation of the cancer cells hence resulted in lower IC 50 with increasing time 65 . Similarly, the results for HeLa cells showed an efficient anticancer effect of HD‐2(TG) nanoparticles where IC 50 values were similar to those for HepG2 cells.…”

Advances in Antitumor Nano-Drug Delivery Systems of 10-Hydroxycamptothecin

“…The NPs are irregularly spherical with uniform particle size, have high drug loading capacity and excellent biocompatibility, and can be rapidly released in the acidic microenvironment of tumor cells. 224 As a natural and renewable biomolecule, dextran is not only biodegradable but also has excellent biocompatibility. 225 Zhao et al constructed HCPT-loaded cinnamaldehyde (CA)-dextran polymers.…”

Nano-drug co-delivery system of natural active ingredients and chemotherapy drugs for cancer treatment: a review

“…They can be used as natural drug carrier for nano-drug delivery, which can improve the bioavailability and efficacy of drugs. At present, ASP (Wang et al., 2020 ), bletilla polysaccharide (Wang et al., 2019a ), Ganoderma lucidum polysaccharide (Zheng et al., 2021a ), ursodeoxycholic acid (MDCA) (Anwar et al., 2018 ), Semen Armeniacae Amarum protein (Lin et al., 2020 ) have been successfully used for the delivery of DOX, MTX, sulfasalazine and PTX. A summary of the studies of natural active components as drug carriers in NDCDS is shown in Table 3 .…”