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.

Platinum(iv) prodrugs of clinically used cisplatin and oxaliplatin with two axial long lipid chains were developed for nanoparticle delivery to combat cisplatin resistance.

Multidrug-resistance (MDR) featuring complicated and poorly defined mechanisms is a major obstacle to the success of cancer chemotherapy in the clinic. Compound nanoparticles comprising multiple cytostatics with different mechanisms of action are commonly developed to tackle the multifaceted nature of clinical MDR. However, the different pharmacokinetics and release profiles of various drugs result in inconsistent drug internalization and suboptimal drug synergy at the tumor sites. In the present study, a type of self-targeting hyaluronate (HA) nanogels (^CDDPHANG/DOX) to reverse drug resistance through the synchronized pharmacokinetics, intratumoral distribution, and intracellular release of topoisomerase II inhibitor doxorubicin (DOX) and DNA-crosslinking agent cisplatin (CDDP) is developed. With prolonged circulation time and enhanced intratumoral accumulation in vivo, ^CDDPHANG/DOX shows efficient drug delivery into the drug-resistant MCF-7/ADR breast cancer cells and enhanced antitumor activity. Besides, fluorescence imaging of DOX combined with the micro-computed tomography (micro-CT) imaging of CDDP facilitates the visualization of this combination tumor chemotherapy. With visualizable synchronized drug delivery, the self-targeting in situ crosslinked nanoplatform may hold good potential in future clinical therapy of advanced cancers.