Synergetic delivery of triptolide and Ce6 with light-activatable liposomes for efficient hepatocellular carcinoma therapy

Abstract

Hepatocellular carcinoma (HCC) has been known as the second common leading cancer worldwide, as it responds poorly to both chemotherapy and medication. Triptolide (TP), a diterpenoid triepoxide, is a promising treatment agent for its effective anticancer effect on multiple cancers including HCC. However, its clinical application has been limited owing to its severe systemic toxicities, low solubility, and fast elimination in the body. Therefore, to overcome the above obstacles, photo-activatable liposomes (LP) integrated with both photosensitizer Ce6 and chemotherapeutic drug TP (TP/Ce6-LP) was designed in the pursuit of controlled drug release and synergetic photodynamic therapy in HCC therapy. The TP encapsulated in liposomes accumulated to the tumor site due to the enhanced permeability and retention (EPR) effect. Under laser irradiation, the photosensitizer Ce6 generated reactive oxygen species (ROS) and further oxidized the unsaturated phospholipids. In this way, the liposomes were destroyed to release TP. TP/Ce6-LP with NIR laser irradiation (TP/Ce6-LP+L) showed the best anti-tumor effect both in vitro and in vivo on a patient derived tumor xenograft of HCC (PDXHCC). TP/Ce6-LP significantly reduced the side effects of TP. Furthermore, TP/Ce6-LP+L induced apoptosis through a caspase-3/PARP signaling pathway. Overall, TP/Ce6-LP+L is a novel potential treatment option in halting HCC progression with attenuated toxicity.

Dynamic Adjust of Non‐Radiative and Radiative Attenuation of AIE Molecules Reinforces NIR‐II Imaging Mediated Photothermal Therapy and Immunotherapy

“…However, the common photothermal agents such as indocyanine green (ICG) and IR780 have aggregation‐caused quenching (ACQ) properties owing to intermolecular interactions ( π – π stacking and other non‐radiative decays), thus tremendously limit their application in cancer phototheranostics. [ 9 , 10 , 11 , 12 ] Since the ideal system for emission and heat production is still limited by the difficulty of blocking strong π – π stacking of molecule in nanoparticles, there is an urgent need to develop effective method to prepare advanced phototheranostic nanoparticles that can produce both high fluorescence and heat for cancer theranostics. The problem is perfectly solved by aggregation‐induced emission (AIE) agents and has received more and more attention in recent years.…”

Exosome CTLA-4 Regulates PTEN/CD44 Signal Pathway in Spleen Deficiency Internal Environment to Promote Invasion and Metastasis of Hepatocellular Carcinoma

“…According to the literature, SD may lead to dysfunction in T cell recognition by disordering the expression of TCRVβ in rats ( Chen et al, 2014 ). In addition, another study reported that immunoregulatory traditional Chinese medicine is beneficial to liver cancer and induces cell apoptosis through the Caspase-3/PARP signaling pathway ( Yu et al, 2021 ). The above studies suggest the importance of the internal environment of SD in the occurrence and development of immune recognition disorders of HCC.…”

Bioresponsive immune-booster-based prodrug nanogel for cancer immunotherapy

“…Various treatments induced translocation of the HMGB1 from nucleus to extracellular matrix, which were examined by immunofluorescence analysis. HMGB1 was a danger signal which activated a series of the related signaling pathways to promote tumorigenesis and proliferation 27 , 28 , 29 , 30 . As shown in Fig.…”

“…Nanotechnology-based drug delivery systems (DDSs) exhibited favorable tumor accumulation and deep tumor penetration 27 , 28 , 29 , 30 , which performed superior therapeutic efficacy in camparison with conventional medicines 31 , 32 , 33 . Nanogels (NGs) formed by intramolecular cross-linking can integrate good biocompatibility, environmental responsiveness, high stability and low toxicity into one single platform, holding a great promise in designing tailored DDSs 34 , 35 , 36 , 37 .…”