Cancer immunotherapies, such as immune checkpoint blockade and chimeric antigen receptor (CAR) T cell therapy, have transformed clinical oncology. However, limited patient response rates and immune-related adverse events remain major clinical challenges. The immunosuppressive tumour microenvironment (TME) has a key role in the response to immunotherapy. The TME of solid tumours can prevent infiltration and negatively affect the activity of immune cells. The immunosuppressive features of the TME can be modulated using biomaterials-based tools that target, respond to and modulate the physicochemical properties of the TME, including hypoxia, acidity, high levels of reactive oxygen species, a dense extracellular matrix and abnormal vasculature. In this Review, we introduce hallmarks of the TME and discuss biomaterials and nanomedicine technologies that can regulate the TME of solid tumours to improve the efficacy of different types of immunotherapy. We outline the remaining challenges in the clinical translation of TME-modulating biomaterials tools and conclude by envisioning future milestones in this field. The tumour microenvironment of solid tumours can prevent immune cell infiltration and negatively affect the efficacy of immunotherapies. This Review discusses the design of biomaterials-based tools that can modulate the physicochemical features of the tumour microenvironment to assist immunotherapies. 

Biomaterials tools to modulate the tumour microenvironment in immunotherapy

Abstract Osteosarcoma, with poor survival after metastasis, is considered the most common primary bone cancer in adolescents. Notwithstanding the efforts of researchers, its five-year survival rate has only shown limited improvement, suggesting that existing therapeutic strategies are insufficient to meet clinical needs. Notably, immunotherapy has shown certain advantages over traditional tumor treatments in inhibiting metastasis. Therefore, managing the immune microenvironment in osteosarcoma can provide novel and valuable insight into the multifaceted mechanisms underlying the heterogeneity and progression of the disease. Additionally, given the advances in nanomedicine, there exist many advanced nanoplatforms for enhanced osteosarcoma immunotherapy with satisfactory physiochemical characteristics. Here, we review the classification, characteristics, and functions of the key components of the immune microenvironment in osteosarcoma. This review also emphasizes the application, progress, and prospects of osteosarcoma immunotherapy and discusses several nanomedicine-based options to enhance the efficiency of osteosarcoma treatment. Furthermore, we examine the disadvantages of standard treatments and present future perspectives for osteosarcoma immunotherapy. 

/pdf/managing-the-immune-microenvironment-of-osteosarcoma-the-2nn6doin.pdf

Managing the immune microenvironment of osteosarcoma: the outlook for osteosarcoma treatment

Pyroptosis has garnered increasing attention in cancer immunotherapy. Moreover, increasing plasma membrane damage by reactive oxygen species (ROS) is considered an effective strategy for promoting pyroptosis. However, the current tactics for enhancing membrane rupture in pyroptosis are limited by the inherent drawbacks of ROS and the immunosuppressive tumor microenvironment. Herein, a self‐adaptive pyroptosis inducer (LPZ) is designed by integrating Lactobacillus rhamnosus GG (LGG) and an enzyme‐like metal‐organic framework to achieve potent pyroptosis immunotherapy. LPZ can adhere to cancer cell membranes through the interaction between the pili of LGG and the mucin of cancer cells. In particular, the adaptive formula can gradually enhance the ability of nanozymes to produce ROS by creating an acidic microenvironment through anaerobic respiration. These results verify that LPZ could generate high levels of ROS both on the membrane and within cancer cells, leading to pyroptotic cell death and strong antitumor immunity. Meanwhile, LGG are eventually killed by ROS in this process to halt their respiration and prevent potential biosafety concerns. Overall, this work provides new inspiration for the design of self‐adaptive nanocatalytic drugs for cancer immunotherapy.

A Self-Adaptive Pyroptosis Inducer: Optimizing the Catalytic Microenvironment of Nanozymes by Membrane-Adhered Microbe Enables Potent Cancer Immunotherapy.

https://doi.org/10.1016/j.apsb.2023.05.016

Light-responsive nanomedicine for cancer immunotherapy

Hypoxia is a hallmark of solid tumors and it significantly contributes to the development of key biological features of tumors, including the microenvironment, migration, invasion, metastasis, pathological angiogenesis, drug resistance, immunosuppression, and poor prognosis. Hypoxia hampers the efficacy of current anti-tumor approaches, including radiotherapy, chemotherapy, immunotherapy, and photodynamic therapy. This has fueled the development of nanomaterials to reoxygenate the tumor’s microenvironment by delivering exogenous O2 or generating O2 in situ as therapeutic approaches per se or to improve the efficacy of current anti-tumor approaches. Herein, we review the recent research progress of nanomaterials for O2 delivery and generation in situ. Their potential transition to the clinics is also discussed. 

Nanomaterials relieving hypoxia for enhanced tumor therapy

Abstract While hypoxia promotes carcinogenesis, tumour aggressiveness, metastasis, and resistance to oncological treatments, the impacts of hyperoxia on tumours are rarely explored because providing a long-lasting oxygen supply in vivo is a major challenge. Herein, we construct micro oxygen factories, namely, photosynthesis microcapsules (PMCs), by encapsulation of acquired cyanobacteria and upconversion nanoparticles in alginate microcapsules. This system enables a long-lasting oxygen supply through the conversion of external radiation into red-wavelength emissions for photosynthesis in cyanobacteria. PMC treatment suppresses the NF-kB pathway, HIF-1α production and cancer cell proliferation. Hyperoxic microenvironment created by an in vivo PMC implant inhibits hepatocarcinoma growth and metastasis and has synergistic effects together with anti-PD-1 in breast cancer. The engineering oxygen factories offer potential for tumour biology studies in hyperoxic microenvironments and inspire the exploration of oncological treatments. 

/pdf/engineering-micro-oxygen-factories-to-slow-tumour-2on7sfsd.pdf

Engineering micro oxygen factories to slow tumour progression via hyperoxic microenvironments

/pdf/engineering-micro-oxygen-factories-to-slow-tumour-r2hmt4qe.pdf

The ability of nanofilms to mimic the natural fiber architecture and form a physical structure that is best suited for skin tissue regeneration makes it an appealing vehicle for skin tissue engineering. However, developing a facile nanofilm with both anti-bacterial and pro-angiogenic activities is yet to be addressed. Herein, two metal ions, including copper (Cu) and silicon (Si), were loaded into Wharton's jelly/polycaprolactone (WJ/PCL) system to prepare a Cu/Si@WJ/PCL nanofilm. These metal ions could impart both anti-bacterial and pro-angiogenic properties to the nanofilms, which could improve their ability in promoting wound healing. The Cu and Si ions were released continuously from the Cu/Si@WJ/PCL nanofilm, which had a nanofibrous structure and random organization. Results derived from the in vitro experiment revealed that the incubated fibroblasts could successfully survive and proliferate under lab conditions, suggesting that the Cu/Si@WJ/PCL nanofilm was cytocompatible. Additionally, the Cu ions released from the nanofilm exhibited effective antibacterial activities against both the gram-positive and gram-negative bacteria, and they acted in conjunction with the released Si ions for improving the tube formation in the human umbilical vein endothelial cells. Additionally, compared to pure WJ/PCL nanofilm and Cu or Si ion-loaded nanofilm, the Cu/Si@WJ/PCL nanofilm significantly accelerated the infected wound healing process in the rat model. The Cu/Si@WJ/PCL nanofilm showed improved epidermal development, vascularization, and collagen deposition compared to the other nanofilms. In this study, a Cu/Si@WJ/PCL nanofilm with pro-angiogenic and anti-bacterial activities was successfully developed, and it could be used as a metal-ion-based therapeutic medium for the treatment of infected wound healing. 

Metal-ion Co-doped Nanofilm with Anti-bacterial and Pro-angiogenic Activities to Accelerate Infected Wound Healing

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Engineering micro oxygen factories to slow tumour progression via hyperoxic microenvironments

Engineering micro oxygen factories to slow tumour progression via hyperoxic microenvironments

Metal-ion Co-doped Nanofilm with Anti-bacterial and Pro-angiogenic Activities to Accelerate Infected Wound Healing