Inhibition of post-surgery tumour recurrence via a hydrogel releasing CAR-T cells and anti-PDL1-conjugated platelets.

The immunosuppressive microenvironment of solid tumours reduces the antitumour activity of chimeric antigen receptor T cells (CAR-T cells). Here, we show that the release-through the implantation of a hyaluronic acid hydrogel-of CAR-T cells targeting the human chondroitin sulfate proteoglycan 4, polymer nanoparticles encapsulating the cytokine interleukin-15 and platelets conjugated with the checkpoint inhibitor programmed death-ligand 1 into the tumour cavity of mice with a resected subcutaneous melanoma tumour inhibits the local recurrence of the tumour as well as the growth of distant tumours, through the abscopal effect. The hydrogel, which functions as a reservoir, facilitates the enhanced distribution of the CAR-T cells within the surgical bed, and the inflammatory microenvironment triggers platelet activation and the subsequent release of platelet-derived microparticles. The post-surgery local delivery of combination immunotherapy through a biocompatible hydrogel reservoir could represent a translational route for preventing the recurrence of cancers with resectable tumours.

Red blood cell-derived nanoerythrosome for antigen delivery with enhanced cancer immunotherapy.

Erythrocytes or red blood cells (RBCs) represent a promising cell-mediated drug delivery platform due to their inherent biocompatibility. Here, we developed an antigen delivery system based on the nanoerythrosomes derived from RBCs, inspired by the splenic antigen-presenting cell targeting capacity of senescent RBCs. Tumor antigens were loaded onto the nanoerythrosomes by fusing tumor cell membrane-associated antigens with nanoerythrosomes. This tumor antigen-loaded nanoerythrosomes (nano-Ag@erythrosome) elicited antigen responses in vivo and, in combination with the anti-programmed death ligand 1 (PD-L1) blockade, inhibited the tumor growth in B16F10 and 4T1 tumor models. We also generated a tumor model showing that "personalized nano-Ag@erythrosomes" could be achieved by fusing RBCs and surgically removed tumors, which effectively reduced tumor recurrence and metastasis after surgery.

In situ thermal ablation of tumors in combination with nano-adjuvant and immune checkpoint blockade to inhibit cancer metastasis and recurrence.

Tumor ablation therapies provide a minimally invasive approach to treat cancer. However, inhibition of cancer metastasis and recurrence after ablation is still a challenge in clinical trials. Here, we propose a strategy using combinatorial thermal ablation, adjuvants and immune checkpoint blockade (ICB) to inhibit metastatic tumor and recurrence via antitumor immune responses post tumor thermal ablation, which are frequently used in the clinic. Furthermore, a strong immune memory against cancer was observed 80 days after the primary tumor was ablated. Considering that all components in our design are approved by Food and Drug Administration (FDA), we provide a strategy based on clinically used cancer treatment technique that is promising in clinical translation.

Leveraging H2 O2 Levels for Biomedical Applications.

Hydrogen peroxide (H2 O2 )-responsive materials have been employed as drug delivery or diagnostic systems to treat or detect diseases with abnormal oxidative stress. A number of H2 O2 -responsive systems have been developed, and they have achieved great progress in controlled drug delivery for disease treatment. However, pathological sites with elevated H2 O2 level, such as cancer and inflammation, have their own characteristics; therefore the material structures and the subsequent formulations should be reasonably designed to acquire maximized therapeutic effects. In this progress report, we overview the development of H2 O2 -responsive functional groups for constructing H2 O2 -responsive formulations, as well as the guidance for designing suitable formulations to treat each specific pathological condition. The challenges and perspectives in this field are also discussed.