Promising Nanomedicines of Shikonin for Cancer Therapy

Abstract

Malignant tumor, the leading cause of death worldwide, poses a serious threat to human health. For decades, natural product has been proven to be an essential source for novel anticancer drug discovery. Shikonin (SHK), a natural molecule separated from the root of Lithospermum erythrorhizon, shows great potential in anticancer therapy. However, its further clinical application is significantly restricted by poor bioavailability, adverse effects, and non-selective toxicity. With the development of nanotechnology, nano drug delivery systems have emerged as promising strategies to improve bioavailability and enhance the therapeutic efficacy of drugs. To overcome the shortcoming of SHK, various nano drug delivery systems such as liposomes, polymeric micelles, nanoparticles, nanogels, and nanoemulsions, were developed to achieve efficient delivery for enhanced antitumor effects. Herein, this review summarizes the anticancer pharmacological activities and pharmacokinetics of SHK. Additionally, the latest progress of SHK nanomedicines in cancer therapy is outlined, focusing on long circulation, tumor targeting ability, tumor microenvironment responsive drug release, and nanosystem-mediated combination therapy. Finally, the challenges and prospects of SHK nanomedicines in the future clinical application are spotlighted.

Shikonin-Loaded Hollow Fe-MOF Nanoparticles for Enhanced Microwave Thermal Therapy

“…Notably, SK can efficiently inhibit cancer glycolysis through the PKM2-mediated pathway and also has many other antitumor bioactivities. − However, the poorly aqueous solubility significantly hinders its practical application. Various nanosystems have been explored for the delivery of SK, including liposomes, polymeric micelles, nanoparticles, nanogels, nanoemulsions, and chimeric advanced drug delivery nanosystems . In this work, SK was loaded to HFM@HA by electrostatic adsorption to prepare a nanomedicine of SK@HFM@HA.…”

“…Various nanosystems have been explored for the delivery of SK, including liposomes, polymeric micelles, nanoparticles, nanogels, nanoemulsions, and chimeric advanced drug delivery nanosystems. 56 In this work, SK was loaded to HFM@HA by electrostatic adsorption to prepare a nanomedicine of SK@ HFM@HA. The loading amount of SK was measured by an UV−vis spectrophotometer based on the standard curve.…”

“…The drug-loading capacity is much higher than that reported previously. 56 Such a high loading capacity may be attributed to the porous and hollow structure. The drug release profiles of HFM@SK@HA were performed in PBS solution with different pH values (7.4 and 5.5) and under the stimulation of MW.…”

Generation of multicellular tumor spheroids via 3D cell culture utilizing a hydrogel comprising chitosan and allylthiourea

“…This diversity can be attributed to factors such as variances in cellularity, extracellular matrix remodeling, and angiogenesis, among others. 14,15…”

“…This diversity can be attributed to factors such as variances in cellularity, extracellular matrix remodeling, and angiogenesis, among others. 14,15 The hydrogel-based 3D culture system provides a threedimensional environment for cells to grow and interact, more closely mimicking the conditions found in the human body and therefore offering a better representation of in vivo conditions. 2 The ability to create a more precise microenvironment in a 3D culture system, with a controlled composition of the hydrogel and physical properties of the environment, can yield a more accurate depiction of how cells will behave in vivo.…”