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Effective systemic therapy is highly desired for the treatment of hepatocellular carcinoma (HCC). In this study, a combination of nanoparticles of poly(L-glutamic acid)- graft -methoxy poly(ethylene glycol)/combretastatin A4 sodium salt (CA4-NPs) plus sorafenib is developed for the cooperative systemic treatment of HCC. The CA4-NPs leads to the disruption of established tumor blood vessels and extensive tumor necrosis, however, inducing increased expression of VEGF-A and angiogenesis. Sorafenib reduces the VEGF-A induced angiogenesis and further inhibits tumor proliferation, cooperating with the CA4-NPs. A significant decrease in tumor volume and prolonged survival time are observed in the combination group of CA4-NPs plus sorafenib compared with CA4-NPs or sorafenib monotherapy in subcutaneous and orthotopic H22 hepatic tumor models. Seventy-one percent of the mice are alive without residual tumor at 96 days post tumor inoculation for the subcutaneous models treated with CA4-NPs 30 or 35 mg·kg−1 plus sorafenib 30 mg·kg−1. Our findings suggest that co-administration of sorafenib and CA4-NPs possesses significant antitumor efficacy for HCC treatment. Effective systemic therapy is highly desired for the treatment of hepatocellular carcinoma (HCC). Herein, we demonstrate that a combination of nanoparticles of poly(L-glutamic acid)- graft -methoxy poly(ethylene glycol)/combretastatin A4 sodium salt (CA4-NPs) plus sorafenib is a promising synergistic approach for systemic treatment of HCC. The CA4-NPs leads to the disruption of established tumor blood vessels and extensive tumor necrosis, however, inducing increased expression of VEGF-A and angiogenesis. Sorafenib reduces the VEGF-A induced angiogenesis and further inhibits tumor proliferation, cooperating with the CA4-NPs. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Gemcitabine is widely used for anticancer therapy. However, its short blood circulation time and poor stability greatly impair its application. To solve this problem, we prepared a poly (l -glutamic acid)- g -methoxy poly (ethylene glycol)-gemcitabine conjugate (l -Gem) with a 14.3 wt% drug-loading content. l -Gem showed concentration- and time-dependent cytotoxicity towards 4T1, LLC, MIA PaCa-2 and A2780 in vitro. Pharmacokinetic and biodistribution studies indicated that l -Gem had remarkably enhanced blood stability, prolonged blood circulation time and greatly improved selective tumor distribution compared with free gemcitabine. The area under the concentration–time curve from zero to infinity [AUC (0–∞) ] of l -Gem in plasma was 43-fold higher than that of free gemcitabine. The AUC (0–∞) of the inactive metabolite, 2′-deoxy-2′,2′-difluorouridine in the l -Gem group was ∼20% of that observed in the free gemcitabine group. The drug tumor accumulation ratio in the l -Gem group relative to the free gemcitabine group was 9.9 at 36 h, while the tumor AUC ratio was 15.8. Testing on Balb/C mice bearing the 4T1 tumor further demonstrated that l -Gem had significantly higher anticancer efficacy than free gemcitabine in vivo. These findings indicated that l -Gem has great potential for cancer treatment. [ABSTRACT FROM AUTHOR]

Immunotherapy has emerged as an effective strategy for the prevention and treatment of a variety of diseases, including cancer, infectious diseases, inflammatory diseases, and autoimmune diseases. Immunomodulatory nanosystems can readily improve the therapeutic effects and simultaneously overcome many obstacles facing the treatment method, such as inadequate immune stimulation, off‐target side effects, and bioactivity loss of immune agents during circulation. In recent years, researchers have continuously developed nanomaterials with new structures, properties, and functions. This Review provides the most recent advances of nanotechnology for immunostimulation and immunosuppression. In cancer immunotherapy, nanosystems play an essential role in immune cell activation and tumor microenvironment modulation, as well as combination with other antitumor approaches. In infectious diseases, many encouraging outcomes from using nanomaterial vaccines against viral and bacterial infections have been reported. In addition, nanoparticles also potentiate the effects of immunosuppressive immune cells for the treatment of inflammatory and autoimmune diseases. Finally, the challenges and prospects of applying nanotechnology to modulate immunotherapy are discussed. [ABSTRACT FROM AUTHOR]