Correction: Relieving immunosuppression during long-term anti-angiogenesis therapy using photodynamic therapy and oxygen delivery.

Correction for 'Relieving immunosuppression during long-term anti-angiogenesis therapy using photodynamic therapy and oxygen delivery' by Qianyuan He , , 2020, , 14788-14800, https://doi.org/10.1039/D0NR02750B.

Tumor cell membrane-based vaccines: A potential boost for cancer immunotherapy.

Because therapeutic cancer vaccines can, in theory, eliminate tumor cells specifically with relatively low toxicity, they have long been considered for application in repressing cancer progression. Traditional cancer vaccines containing a single or a few discrete tumor epitopes have failed in the clinic, possibly due to challenges in epitope selection, target downregulation, cancer cell heterogeneity, tumor microenvironment immunosuppression, or a lack of vaccine immunogenicity. Whole cancer cell or cancer membrane vaccines, which provide a rich source of antigens, are emerging as viable alternatives.

A self-assembled, genetically engineered, irradiated tumor cell debris vaccine.

Vaccine-based therapeutics for cancers face several challenges including lack of immunogenicity and tumor escape pathways for single antigen targets. It has been reported that radiotherapy has an in situ vaccine effect that provides tumor antigens following irradiation, helping to activate antigen-presenting cells (APCs). Herein, a new vaccine approach is developed by combining genetically engineered irradiated tumor cell debris (RTD) and hyaluronic acid (HA), termed HA@RTD.

A broadly applicable protein-polymer adjuvant system for antiviral vaccines.

Although protein subunit vaccines generally have acceptable safety profiles with precise antigenic content, limited immunogenicity can lead to unsatisfactory humoral and cellular immunity and the need for vaccine adjuvants and delivery system. Herein, we assess a vaccine adjuvant system comprising Quillaja Saponaria-21(QS-21) and cobalt porphyrin polymeric micelles that enabling the display of His-tagged antigen on its surface. The nanoscale micelles promote antigen uptake and dendritic cell activation to induce robust cytotoxic T lymphocyte response and germinal center formation.

Irradiated microparticles suppress prostate cancer by tumor microenvironment reprogramming and ferroptosis.

Immunogenic cell death (ICD) plays a crucial role in triggering the antitumor immune response in the tumor microenvironment (TME). Recently, considerable attention has been dedicated to ferroptosis, a type of ICD that is induced by intracellular iron and has been demonstrated to change the immune desert status of the TME. However, among cancers that are characterized by an immune desert, such as prostate cancer, strategies for inducing high levels of ferroptosis remain limited.

Applications of Intravital Imaging in Cancer Immunotherapy.

Currently, immunotherapy is one of the most effective treatment strategies for cancer. However, the efficacy of any specific anti-tumor immunotherapy can vary based on the dynamic characteristics of immune cells, such as their rate of migration and cell-to-cell interactions. Therefore, understanding the dynamics among cells involved in the immune response can inform the optimization and improvement of existing immunotherapy strategies.

Engineering irradiated tumor-derived microparticles as personalized vaccines to enhance anti-tumor immunity.

The inadequate activation of antigen-presenting cells, the entanglement of T cells, and the highly immunosuppressive conditions in the tumor microenvironment (TME) are important factors that limit the effectiveness of cancer vaccines. Studies show that a personalized and broad antigen repertoire fully activates anti-tumor immunity and that inhibiting the function of transforming growth factor (TGF)-β facilitates T cell migration. In our study, we introduce a vaccine strategy by engineering irradiated tumor cell-derived microparticles (RT-MPs), which have both personalized and broad antigen repertoire, to induce comprehensive anti-tumor effects.

HSF1 protects cells from cadmium toxicity by governing proteome integrity.

Background: Cadmium toxicity has been associated with disruption of protein homeostasis by interfering with protein folding processes. Heat shock factor 1 (HSF1) coordinates the rapid and extensive cellular response to maintain proteomic balance facing the challenges from many environmental stressors. Thus, we suspect that HSF1 may shield cells from cadmium toxicity by conserving proteome integrity.

The tumour-promoting role of protein homeostasis: Implications for cancer immunotherapy.

Protein homeostasis, an important aspect of cellular fitness that encompasses the balance of production, folding and degradation of proteins, has been linked to several diseases of the human body. Multiple interconnected pathways coordinate to maintain protein homeostasis within the cell. Recently, the role of the protein homeostasis network in tumorigenesis and tumour progression has gradually come to light.

The roles of inflammasomes in cancer.

Inflammation is a key characteristic of all stages of tumor development, including tumor initiation, progression, malignant transformation, invasion, and metastasis. Inflammasomes are an important component of the inflammatory response and an indispensable part of the innate immune system. Inflammasomes regulate the nature of infiltrating immune cells by signaling the secretion of different cytokines and chemokines, thus regulating the anti-tumor immunity of the body.

Ferroptosis-Enhanced Immunotherapy with an Injectable Dextran-Chitosan Hydrogel for the Treatment of Malignant Ascites in Hepatocellular Carcinoma.

Malignant ascites in advanced hepatocellular carcinoma (HCC) is a complex clinical problem that lacks effective treatments. Due to the insensitivity of advanced HCC cells to traditional chemotherapies, low drug accumulation, and limited drug residence time in the peritoneal cavity, the therapeutic effects of malignant ascites in HCC are not satisfactory. In this study, an injectable hydrogel drug delivery system based on chitosan hydrochloride and oxidized dextran (CH-OD) is designed to load sulfasalazine (SSZ), an FDA-approved drug with ferroptosis-inducing ability, for effective tumor-killing and activation of anti-tumor immunity.

Sustained release of tumor cell lysate and CpG from an injectable, cytotoxic hydrogel for melanoma immunotherapy.

Many basic research studies have shown the potential of autologous cancer vaccines in the treatment of melanoma. However, some clinical trials showed that simplex whole tumor cell vaccines can only elicit weak CD8 T cell-mediated antitumor responses which were not enough for effective tumor elimination. So efficient cancer vaccine delivery strategies with improved immunogenicity are needed.

Cupric-ion-promoted fabrication of oxygen-replenishing nanotherapeutics for synergistic chemo and photodynamic therapy against tumor hypoxia.

Mixing a glutathione (GSH)-responsive carboxy zinc(II) phthalocyanine (ZnPc*) and CuSO·5HO in water with or without the presence of the anticancer drug SN38 resulted in the formation of self-assembled nanotherapeutics labeled as ZnPc*/Cu/SN38@NP and ZnPc*/Cu@NP, respectively. The Cu ions not only promoted the self-assembly of the carboxy phthalocyanine through metal complexation, but also catalyzed the transformation of HO to oxygen via a catalase-like reaction, rendering an oxygen-replenishing property to the nanosystems. Both nanosystems exhibited high stability in aqueous media, but the nanoparticles disassembled gradually in an acidic or GSH-enriched environment and inside human colorectal adenocarcinoma HT29 cells, releasing the encapsulated therapeutic components.

Engineered Microparticles for Treatment of Murine Brain Metastasis by Reprograming Tumor Microenvironment and Inhibiting MAPK Pathway.

Brain metastases (BRM) are common in advanced lung cancer. However, their treatment is challenging due to the blood-brain barrier (BBB) and the immunosuppressive tumor microenvironment (ITME). Microparticles (MPs), a type of extracellular vesicle, can serve as biocompatible drug delivery vehicles that can be further modulated with genetic engineering techniques.

Hierarchical Supramolecular Self-Assembly: Fabrication and Visualization of Multiblock Microstructures.

Due to the fast dynamics and re-equilibration of supramolecular self-assembly, bottom-up molecular strategies to fabricate well-defined and controllable multiblock structures are rare. Herein, we propose a new concept for fabrication of fluorescent multiblock microcolumns containing 1 to 7 blocks via hierarchical supramolecular self-assembly based on cucurbit[8]uril (CB[8]), NaBr and an AIEgen guest. Through the complexation between CB[8] and different numbers of AIEgen guests (2, 1, 0), the competitive displacement caused by the binding of the sodium cation to the CB[8] portal, and the reversible assembly of positively charged guests in salt solutions, one-pot hierarchical supramolecular self-assembly is realized.

Self-adjuvanting cancer nanovaccines.

Nanovaccines, a new generation of vaccines that use nanoparticles as carriers and/or adjuvants, have been widely used in the prevention and treatment of various diseases, including cancer. Nanovaccines have sparked considerable interest in cancer therapy due to a variety of advantages, including improved access to lymph nodes (LN), optimal packing and presentation of antigens, and induction of a persistent anti-tumor immune response. As a delivery system for cancer vaccines, various types of nanoparticles have been designed to facilitate the delivery of antigens and adjuvants to lymphoid organs and antigen-presenting cells (APCs).

Ionizing Radiation-Induced Tumor Cell-Derived Microparticles Prevent Lung Metastasis by Remodeling the Pulmonary Immune Microenvironment.

Purpose: The majority of cancer-related deaths are attributed to metastasis rather than localized primary tumor progression. However, the factors that regulate the premetastatic niche (PMN) and metastasis have not yet been clearly elucidated. We investigated the antimetastatic effects of irradiated tumor cell-derived microparticles (RT-MPs) and highlighted the role of innate immune cells in PMN formation.

Microparticles: biogenesis, characteristics and intervention therapy for cancers in preclinical and clinical research.

Extracellular vesicles (EVs), spherical biological vesicles, mainly contain nucleic acids, proteins, lipids and metabolites for biological information transfer between cells. Microparticles (MPs), a subtype of EVs, directly emerge from plasma membranes, and have gained interest in recent years. Specific cell stimulation conditions, such as ultraviolet and X-rays irradiation, can induce the release of MPs, which are endowed with unique antitumor functionalities, either for therapeutic vaccines or as direct antitumor agents.

Injectable Hydrogel as a Unique Platform for Antitumor Therapy Targeting Immunosuppressive Tumor Microenvironment.

Cancer immunotherapy can boost the immune response of patients to eliminate tumor cells and suppress tumor metastasis and recurrence. However, immunotherapy resistance and the occurrence of severe immune-related adverse effects are clinical challenges that remain to be addressed. The tumor microenvironment plays a crucial role in the therapeutic efficacy of cancer immunotherapy.

Targeting senescence-like fibroblasts radiosensitizes non-small cell lung cancer and reduces radiation-induced pulmonary fibrosis.

Cancer cell radioresistance is the primary cause of the decreased curability of non-small cell lung cancer (NSCLC) observed in patients receiving definitive radiotherapy (RT). Following RT, a set of microenvironmental stress responses is triggered, including cell senescence. However, cell senescence is often ignored in designing effective strategies to resolve cancer cell radioresistance.

Secretions from hypochlorous acid-treated tumor cells delivered in a melittin hydrogel potentiate cancer immunotherapy.

Autologous tumor cells and cell-derived secretions (CDS) can induce antitumor immune responses. The conditions in which cells are cultured and treated impact CDS, and cellular insults alter their composition and function. In this study, we generated CDS from tumor cells exposed to normal culture conditions, hypoxia, cisplatin, radiotherapy, photodynamic therapy, or hypochlorous acid (HOCl).

Local biomaterial-assisted antitumour immunotherapy for effusions in the pleural and peritoneal cavities caused by malignancies.

Malignant pleural effusion (MPE) and malignant ascites (MA), which are common but serious conditions caused by malignancies, are related to poor quality of life and high mortality. Current treatments, including therapeutic thoracentesis and indwelling pleural catheters or paracentesis and catheter drainage, are largely palliative. An effective treatment is urgently needed.

Encapsulating an acid-activatable phthalocyanine-doxorubicin conjugate and the hypoxia-sensitive tirapazamine in polymeric micelles for multimodal cancer therapy.

A zinc(ii) phthalocyanine (ZnPc) was conjugated to doxorubicin (Dox) via an acid-labile hydrazone linker. The resulting ZnPc-Dox conjugate was then encapsulated into polymeric micelles formed through self-assembly of a block copolymer of poly(ethylene glycol) and poly(d,l-lactide) both in the absence and presence of the hypoxia-activated prodrug tirapazamine (TPZ) to give ZnPc-Dox@micelles and ZnPc-Dox/TPZ@micelles respectively. These polymeric micelles exhibited an excellent stability in aqueous media, but underwent disassembly in an acidic environment.

Role of nanoparticle-mediated immunogenic cell death in cancer immunotherapy.

Cancer immunotherapy, which suppresses cancer progression by activating the anti-cancer immunity of patients, shows utility in treating multiple types of cancers. Immunogenic cell death (ICD) induced by most clinical treatment modalities plays a critical role in promoting cancer immunotherapy by releasing tumor-associated antigens and neoantigens and exposing "danger signals" to stimulate immune cells. This comment article presents the different roles of nanoparticles in various treatment modalities of cancers, including chemotherapy, radiotherapy, photodynamic and photothermal therapies, and therapy with radiated tumor cell-released nanoparticles, which often activate anti-cancer immunological effects by inducing ICD of cancer cells, and highlights the challenges and opportunities of ICD-related cancer immunotherapy in the clinic.