A novel redox-responsive ursolic acid polymeric prodrug delivery system for osteosarcoma therapy

Abstract

Ursolic acid (UA), found widely in nature, exerts effective anti-tumoral activity against various malignant tumors. However, the low water solubility and poor bioavailability of UA have greatly hindered its translation to the clinic. To overcome these drawbacks, a simple redox-sensitive UA polymeric prodrug was synthesized by conjugating UA to polyethylene glycol using a disulfide bond. This formulation can self-assemble into micelles (U-SS-M) in aqueous solutions to produce small size micelles ($62.5 nm in diameter) with high drug loading efficiency ($16.7%) that exhibit pH and reduction dual-sensitivity. The cell and animal studies performed using the osteosarcoma MG-63 cell line and MG-63 cancer xenograft mice as the model systems consistently confirmed that the U-SS-M formulation could significantly prolong the circulation in blood and favor accumulation in tumor tissue. Targeted accumulation allows the U-SS-M to be effectively internalized by cancer cells, where the rapid release of UA is favored by a glutathione-rich and acidic intracellular environment, and ultimately achieves potent antitumor efficacy.

Nanoparticles use for Delivering Ursolic Acid in Cancer Therapy: A Scoping Review

“…From the results of relative body weight calculations contained in Table 6, no significant differences existed in the weight of the mice, proving that nanoparticle administration neither caused side effects nor produced symptoms of toxicity (Poudel et al, 2020;Liu et al, 2021;Fu et al, 2021). This result is also supported by other toxicity data presented in Table 7, which shows that there was no clear cell damage and no morphological changes in the major organs i.e.…”

“…In tumor tissue, the concentration of UA decreases over time, although the amount delivered by the polymer-drug conjugate gradually increases. The concentration of U-SS-M in tumor tissue is significantly higher than that of native UA at both 6 and 12 h after administration (Fu et al, 2021).…”

“…IR (%) or TGI (%) W T of negative control group − W T of treatment group W T of negative control group where W T is the weight of the tumor (Wang et al, 2017;Shen et al, 2018;Fu et al, 2021). In this study, the relative tumor weight and relative inhibition rate were each calculated using the following formulas:…”

Redox-sensitive iodinated polymersomes carrying histone deacetylase inhibitor as a dual-functional nano-radiosensitizer for enhanced radiotherapy of breast cancer

“…In this study, we designed redox-sensitive iodinated polymersomes (RIP) carrying SAHA, as a dual-functional nano-radiosensitizer for enhanced breast cancer radiotherapy ( Scheme 1 ). RIP is disulfide-crosslinked to improve its stability and accelerate intracellular drug release, as reported previously for delivery of different drugs (Liu et al., 2020 ; Fu et al., 2021 ; Gong et al., 2021 ). RIP not only possesses a high iodine content of 55.4 wt.% but also efficiently loads and delivers SAHA into tumor cells.…”

Novel ROS-responsive marine biomaterial fucoidan nanocarriers with AIE effect and chemodynamic therapy

“…High ROS levels have been widely used in the development of stimulus-responsive drug delivery systems. Compared with widely used intrinsic signals such as pH and GSH, ROS in tumor tissues has higher speci city [17][18][19][20].…”