Reducing Postoperative Recurrence of Early‐Stage Hepatocellular Carcinoma by a Wound‐Targeted Nanodrug

Abstract

New strategies to decrease risk of relapse after surgery are needed for improving 5‐year survival rate of hepatocellular carcinoma (HCC). To address this need, a wound‐targeted nanodrug is developed, that contains an immune checkpoint inhibitor (anti‐PD‐L1)and an angiogenesis inhibitor (sorafenib)). These nanoparticles consist of highly biocompatible mesoporous silica (MSNP) that is surface‐coated with platelet membrane (PM) to achieve surgical site targeting in a self‐amplified accumulation manner. Sorafenib is introduced into the MSNP pores while covalently attaching anti‐PD‐L1 antibody on the PM surface. The resulting nano‐formulation, abbreviated as a‐PM‐S‐MSNP, can effectively target the surgical margin when intraperitoneally (IP) administered into an immune competent murine orthotopic HCC model. Multiple administrations of a‐PM‐S‐MSNP generate potent anti‐HCC effect and significantly prolong overall mice survival. Immunophenotyping and immunochemistry staining reveal the signatures of favorable anti‐HCC immunity and anti‐angiogenesis effect at tumor sites. More importantly, microscopic inspection of a‐PM‐S‐MSNP treated mice shows that 2 out 6 are histologically tumor‐free, which is in sharp contrast to the control mice where tumor foci can be easily identified. The data suggest that a‐PM‐S‐MSNP can efficiently inhibit post‐surgical HCC relapse without obvious side effects and holds considerable promise for clinical translation as a novel nanodrug.

Revolutionising hepatocellular carcinoma surveillance: Harnessing contrast-enhanced ultrasound and serological indicators for postoperative early recurrence prediction

“…[5] Effectively addressing the challenge of early recurrence and improving treatment outcomes necessitates the implementation of effective strategies, such as perioperative targeted therapy, immunotherapy, and transarterial chemoembolisation (TACE). [6][7][8][9] These approaches aim to target the residual tumor cells and impede their growth and dissemination postoperatively. However, accurately predicting which patients are at a high risk of early recurrence remains a complex task in clinical practice.…”

Nanomaterial-Based Antivascular Therapy in the Multimodal Treatment of Cancer

“…In 2020, the FDA approved ICIs in combination with anti-angiogenic drugs for the treatment of patients with inoperable HCC or patients with HCC ineligible for transplantation [51]. Some studies have shown that antivascular strategies combined with immune checkpoint blockade can effectively improve the efficacy of immunotherapy [45,52]. VEGF can prevent T cells from infiltrating tumors by promoting endothelial nonreactivity; thus, it inhibits the anticancer effect of ICIs and leads to the apoptosis of CD8 + T cells.…”

Immunotherapy-based novel nanoparticles in the treatment of gastrointestinal cancer: Trends and challenges

“…Moreover, combination with anti-PD-1 therapy can reverse the inhibitory immune microenvironment of HCC. To solve the problem of HCC recurrence after surgery, Li et al [ 84 ] designed a bionic NDDS consisting of MSNPs loaded with anti-PD-L1 and sorafenib and coated with platelet membranes at the surface of the MSNPs. This NDDS can target wounds and generate potent anti-HCC immunity, providing a new therapeutic idea for preventing recurrence in postsurgery HCC patients.…”