A comprehensive overview of triptolide utilizing nanotechnology and its potential applications in prostate diseases

Abstract

Triptolide (TPL) demonstrates a broad spectrum of biological and pharmacological activities, with its primary effects encompassing anti-inflammatory and anti-tumor properties, thereby rendering it applicable in the treatment of various diseases. However, the toxicity associated with TPL has considerably limited its clinical application. In recent years, the advancement of functional nanotechnology has created new opportunities for the application of TPL. TPL has been formulated using nanotechnology, resulting in a stable and tightly bound preparation. Regarding nanoparticle release, TPL can rapidly release the drug in acidic environments, such as tumor tissues, through pH-sensitive nanoparticles, while releasing the drug slowly under normal pH conditions. Furthermore, the surface characteristics and particle size of the carrier can be adjusted to control the drug release rate, thereby enhancing efficacy and reducing side effects. In terms of nanotargeting, active targeting achieved through surface modification can increase the concentration of the drug at the lesion site. Nanotechnology enhances the effectiveness of TPL, underscores its clinical advantages and potential, improves its disease-related performance, and offers novel strategies for disease treatment. This strategy is essential for improving therapeutic efficacy while minimizing side effects and enhancing bioavailability. Nano-TPL exhibits considerable potential for clinical application, owing to its effective targeted anti-inflammatory and anti-tumor properties, as well as its minimal toxic side effects. In this review, we present a succinct summary of the pharmacological activities and adverse effects of TPL, modifications made to its delivery system via nanotechnology, and its clinical application prospect is exemplified by prostate disease.

Keywords: anti-inflammatory; anti-tumor; nanotechnology; prostate diseases; triptolide.

FIGURE 1

Schematic representation of different types of commonly used TPL nanocarriers. The diagram illustrates various types of commonly used TPL nanocarriers: TPL preparation of hydrophilic and lipophilic emulsions; Formation of liposomes (TP-LP) via the thin film dispersion method; Modification of liposomes with transferrin on their surface to create transferrin-modified liposomes (Tf-Tp@Lip); Development of polymeric micelles; Synthesis of TPL solid lipid nanoparticles (TCM) through a process involving pre-emulsion, emulsion, dispersion, and solid nanoparticles; and Creation of pH-stimulated responsive nanocarriers using a specific polymer through film evaporation hydration.

FIGURE 2

Intravascular release and mechanism of pH-responsive TwHF nanocarrier. Folate-conjugated F127, pH-sensitive peptides, and TwHF were co-assembled to construct a pH-responsive nanocarrier for the drug TwHF. In the in vivo environment, the TwHF nanoparticles are transported to inflammatory areas via blood vessels, where they disassemble due to the reduced pH at these sites. This process facilitates the release of TPL, allowing it to exert its anti-inflammatory and anti-tumor activities at the targeted locations. At inflammatory sites, TwHF exhibits various mechanisms of action on different cell types: it is absorbed by endothelial cells, inhibiting the release of adhesion factors VCAM-1 and ICAM-2 through the inhibition of the IKK signaling pathway, thereby reducing the adhesion of these factors to endothelial cells. In Th17 cells, it suppresses the transcription and translation of the pro-inflammatory factors IL-17 and the chemokine MMP-9 by inhibiting the SMADs and RORγT signaling pathways. In macrophages, TwHF promotes the differentiation of macrophages into M1 macrophages by inhibiting the JAK, STAT1, MyD88, and NF-kB signaling pathways. Concurrently, it enhances the activation of the JAK, STAT3, and STAT6 signaling pathways through the promotion of PPAR-γ signaling, further facilitating the differentiation of macrophages into M2 macrophages. In inflammatory cells, TwHF can inhibit the synthesis of pro-inflammatory cytokines and proteins by targeting IKKs, NF-kB (P65), and TAK1 signaling pathways, and by interfering with the translation program of RNA polymerase II.