Dynamic Covalent Hydrogel as a Single-Dose Vaccine Adjuvant for Sustained Antigen Release and Significantly Elevated Humoral Immunity.

Vaccine is the most important way for fighting against infection diseases. However, multiple injections and unsatisfied immune responses are the main obstacles for current vaccine application. Herein, a dynamic covalent hydrogel (DCH) is used as a single-dose vaccine adjuvant for eliciting robust and sustained humoral immunity.

Fusobacterium nucleatum carcinogenesis and drug delivery interventions.

The microbiome has emerged as a significant biomarker and modulator in cancer development and treatment response. Recent research highlights the notable role of Fusobacterium nucleatum (F. nucleatum) in various tumor types, including breast, colorectal, esophageal, gastric, pancreatic, and lung cancers.

Anti-stromal nanotherapeutics for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), the most commonly diagnosed primary liver cancer, has become a leading cause of cancer-related death worldwide. Accumulating evidence confirms that the stromal constituents within the tumor microenvironment (TME) exacerbate HCC malignancy and set the barriers to current anti-HCC treatments. Recent developments of nano drug delivery system (NDDS) have facilitated the application of stroma-targeting therapeutics, disrupting the stromal TME in HCC.

Killing tumor-associated bacteria with a liposomal antibiotic generates neoantigens that induce anti-tumor immune responses.

Increasing evidence implicates the tumor microbiota as a factor that can influence cancer progression. In patients with colorectal cancer (CRC), we found that pre-resection antibiotics targeting anaerobic bacteria substantially improved disease-free survival by 25.5%.

The tumor therapeutic potential of long non-coding RNA delivery and targeting.

Long non-coding RNAs (lncRNAs) is a type of RNA over 200 nt long without any protein coding ability, which has been investigated relating to crucial biological function in cells. There are many key lncRNAs in tumor/normal cells that serve as a biological marker or a new target for tumor treatment. However, compared to some small non-coding RNA, lncRNA-based drugs are limited in clinical application.

Nano Delivery of Chemotherapeutic ICD Inducers for Tumor Immunotherapy.

Immunogenic cell death (ICD, also known as immunogenic apoptosis) of malignant cells is confirmed to activate the host immune system to prevent, control, and eliminate tumors. Recently, a range of chemotherapeutic drugs have been repurposed as ICD inducers and applied for tumor immunotherapy. However, several hurdles to the widespread application of chemotherapeutic ICD inducers remain, namely poor water solubility, short blood circulation, non-specific tissue distribution, and severe toxicity.

Emerging Epigenetic-Based Nanotechnology for Cancer Therapy: Modulating the Tumor Microenvironment.

Dysregulated epigenetic modifications dynamically drive the abnormal transcription process to affect the tumor microenvironment; thus, promoting cancer progression, drug resistance, and metastasis. Nowadays, therapies targeting epigenetic dysregulation of tumor cells and immune cells in the tumor microenvironment appear to be promising adjuncts to other cancer therapies. However, the clinical results of combination therapies containing epigenetic agents are disappointing due to systemic toxicities and limited curative effects.

Fibrotic immune microenvironment remodeling mediates superior anti-tumor efficacy of a nano-PD-L1 trap in hepatocellular carcinoma.

The local microenvironment where tumors develop can shape cancer progression and therapeutic outcome. Emerging evidence demonstrate that the efficacy of immune-checkpoint blockade (ICB) is undermined by fibrotic tumor microenvironment (TME). The majority of hepatocellular carcinoma (HCC) develops in liver fibrosis, in which the stromal and immune components may form a barricade against immunotherapy.

Nanodelivery of cGAS-STING activators for tumor immunotherapy.

Activation of the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway has great potential to promote antitumor immunity. Development of activators for the cGAS-STING pathway (cGAS-STING activators) has profoundly revolutionized tumor immunotherapy. However, successful clinical application of cGAS-STING activators is contingent on having appropriate systems to achieve safe, effective, and specific delivery.

Formulation of two lipid-based membrane-core nanoparticles for FOLFOX combination therapy.

FOLFOX is a combination of folinic acid (FnA), 5-fluorouracil (5-Fu) and oxaliplatin (OxP). It has been used as the standard treatment for colorectal cancer (CRC) and hepatocellular carcinoma (HCC). This treatment is effective, but its high toxicity is dose limiting, and the drugs need to be taken for a long time.

Strategies targeting tumor immune and stromal microenvironment and their clinical relevance.

The critical role of tumor microenvironment (TME) in tumor initiation and development has been well-recognized after more than a century of studies. Numerous therapeutic approaches targeting TME are rapidly developed including those leveraging nanotechnology, which have been further accelerated since the emergence of immune checkpoint blockade therapies in the past decade. While there are many reviews focusing on TME remodeling therapies via drug delivery and engineering strategies in animal models, state-of-the-art evaluation of clinical development states of TME-targeted therapeutics is rarely found.

Nano-trapping CXCL13 reduces regulatory B cells in tumor microenvironment and inhibits tumor growth.

Interactions between different cell types in the tumor microenvironment (TME) affect tumor growth. Tumor-associated fibroblasts produce C-X-C motif chemokine ligand 13 (CXCL13) which recruits B cells to the TME. B-cells in the TME differentiate into regulatory B cells (Bregs) (IL-10CD1dCD5CD138CD19).

A Minimalist Binary Vaccine Carrier for Personalized Postoperative Cancer Vaccine Therapy.

In recent years, significant evolutions have been made in applying nanotechnologies for prophylactic and therapeutic cancer vaccine design. However, the clinical translation of nanovaccines is still limited owing to their complicated compositions and difficulties in the spatiotemporal coordination of antigen-presenting cell activation and antigen cross-presentation. Herein, a minimalist binary nanovaccine (BiVax) is designed that integrates innate stimulating activity into the carrier to elicit robust antitumor immunity.

Nano delivery of simvastatin targets liver sinusoidal endothelial cells to remodel tumor microenvironment for hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) developed in fibrotic liver does not respond well to immunotherapy, mainly due to the stromal microenvironment and the fibrosis-related immunosuppressive factors. The characteristic of liver sinusoidal endothelial cells (LSECs) in contributing to fibrosis and orchestrating immune response is responsible for the refractory to targeted therapy or immunotherapy of HCC. We aim to seek a new strategy for HCC treatment based on an old drug simvastatin which shows protecting effect on LSEC.

Novel Pyropheophorbide Phosphatydic Acids Photosensitizer Combined EGFR siRNA Gene Therapy for Head and Neck Cancer Treatment.

This study combined two novel nanomedicines, a novel LCP Pyro PA photodynamic therapy (PDT) and LCP EGFR siRNA gene therapy, to treat head and neck cancer. A novel photosensitizer, pyropheophorbide phosphatydic acids (Pyro PA), was first modified into Lipid-Calcium phosphate nanoparticles named LCP Pyro PA NPs, and targeted with aminoethylanisamide as a novel PDT photosensitizer. EGFR siRNA was encapsulated into LCP NPs to silence EGFR expression.

Manipulating Liver Bile Acid Signaling by Nanodelivery of Bile Acid Receptor Modulators for Liver Cancer Immunotherapy.

Gut bacteria and their metabolites influence the immune microenvironment of liver through the gut-liver axis, thus representing emerging therapeutic targets for liver cancer therapy. However, directly manipulating gut microbiota or their metabolites is not practical in clinic since the safety concerns and the complicated mechanism of action. Considering the dysregulated bile acid profiles associated with liver cancer, here we propose a strategy that directly manipulates the primary and secondary bile acid receptors through nanoapproach as an alternative and more precise way for liver cancer therapy.

Therapeutic and delivery strategies of phytoconstituents for renal fibrosis.

Chronic kidney disease (CKD) is one of the most common diseases endangering human health and life. By 2030, 14 per 100,000 people may die from CKD. Renal fibrosis (RF) is an important intermediate link and the final pathological change during CKD progression to the terminal stage.

Preparation and Characterization of siRNA-Loaded Liposomes.

The major challenge for RNAi-based therapy is the fabrication of the delivery system that meet the requirement of clinical applicability. Liposome-derived nanoparticles (NPs) are one of the best investigated systems for in vivo siRNA delivery. In the recent years, we have successfully redesigned the conventional cationic liposomes into Liposome/Protamine/hyaluronic acid (LPH) NPs and Lipid-Calcium-Phosphate (LCP) NPs in order to increase the in vivo gene silencing effect and reduce the toxicity.

Tinagl1 Gene Therapy Suppresses Growth and Remodels the Microenvironment of Triple Negative Breast Cancer.

Triple negative breast cancer (TNBC) remains one of the most challenging subtypes of breast cancer to treat and is responsible for approximately 12% of breast cancer cases in the US per year. In 2019, the protein Tinagl1 was identified as a key factor for improved prognoses in certain TNBC patients. While the intracellular mechanism of action has been thoroughly studied, little is known about the role of Tinagl1 in the tumor microenvironment.

Macrophage-Mediated Tumor Cell Phagocytosis: Opportunity for Nanomedicine Intervention.

Macrophages are one of the most abundant non-malignant cells in the tumor microenvironment, playing critical roles in mediating tumor immunity. As important innate immune cells, macrophages possess the potential to engulf tumor cells and present tumor-specific antigens for adaptive antitumor immunity induction, leading to growing interest in targeting macrophage phagocytosis for cancer immunotherapy. Nevertheless, live tumor cells have evolved to evade phagocytosis by macrophages via the extensive expression of anti-phagocytic molecules, such as CD47.