A Hepatocellular Carcinoma Targeting Nanostrategy with Hypoxia-Ameliorating and Photothermal Abilities that, Combined with Immunotherapy, Inhibits Metastasis and Recurrence

Abstract

Hepatocellular carcinoma (HCC) is a common and highly malignant tumor that is prone to recurrence and metastasis and has no effective treatment. Unsurprisingly, its prognosis is quite poor; early detection methods and effective low-toxicity treatments are urgently needed. To achieve these goals, we designed a multifunctional, U.S. Food and Drug Administration-approved Prussian blue (PB) nanoparticle (NP) with a porous metal organic frame loaded with sorafenib (SF), conjugated with HCC-specific targeting peptide SP94 and the near-infrared dye cyanine (Cy)5.5. These NPs are amenable to multimodal imaging for dynamic monitoring of their biodistribution and tumor-targeting effects. The SP94-PB-SF-Cy5.5 NPs achieved targeted delivery and controlled SF release and exhibited good photothermal effects. In this strategy, photothermal therapy and SF treatment complement each other, reducing the side effects of SF and achieving a therapeutic effect without local tumor recurrence. In addition, the catalase-like ability of the NPs alleviates tumor hypoxia, and their photothermal effects induce immunogenic cell death, leading to the release of tumor-associated antigens. These effects combine to trigger an antitumor immune response; the NPs also displayed promising inhibitory effects on tumor metastasis and recurrence and produced an abscopal effect and long-term immunological memory when combined with antiprogrammed death-ligand 1 (PD-L1) immunotherapy. These safe, multifunctional NPs represent a valuable treatment option for HCC. In addition, this next-generation treatment model may provide some ideas for the management of HCC and other cancers.

Immune signature-based hepatocellular carcinoma subtypes may provide novel insights into therapy and prognosis predictions

“…HCC is a leading cause of cancer-related mortality, with most patients in advanced stages of the disease when they are initially diagnosed [ 40 ]. These advanced-stage patients, with high rates of recurrence and metastases, are no longer good candidates for surgical resection [ 40 , 41 ]. HCC carcinogenesis and progression are complex, with interactions between a variety of genetic backgrounds and tumour microenvironments.…”

Synergistic effect of toosendanin and regorafenib against cell proliferation and migration by regulating WWOX signaling pathway in hepatocellular carcinoma

“…Despite extensive efforts to develop novel drugs and therapeutic strategies over the past decade, a single drug generally achieves limited therapeutic effects toward HCC (T. Zhou et al, 2020). Therefore, novel therapeutic approaches such as combining therapy are needed to enhance the efficacy of treatment.…”

Biocompatible nanoreactors of catalase and nanozymes for anticancer therapeutics

“…Therefore, such immunomodulation strategies towards multimodal imaging for dynamic monitoring of biodistribution of functionalized nanoparticles and their tumor‐targeting effects have transformed into a synergistic between PDT and immunotherapy. [ 116 ] In this process, targeted delivery and controlled release of drug while being conjugated with specific targetting peptide attached with fluorescent dye cyanine (Cy)5.5 turn the nanosystem capable of multimodal imaging for their biodistribution check.…”