Nanoparticles intratumoral injection

Objective: Polyethylene glycol-modified gold nanostar particles (GNS-PEG) were constructed to investigate whether the degradation of extracellular matrix in triple-negative breast cancer could improve the tumor delivery of GNS-PEG and enhance the efficacy of photothermal therapy. Methods: GNS-PEG were constructed and characterized for physicochemical properties as well as photothermal properties. At the cellular level, the cytotoxicity of halofuginone (HF) and the effect of photothermal therapy were detected...

Tumor-associated macrophages (TAMs)-representative immune-suppressive cells in the tumor microenvironment (TME)-are known to promote tumor progression and metastasis, and thus have been considered an attractive target for cancer therapy. However, current TAM-targeting strategies are insufficient to result in robust antitumor efficacy. Here, we report a small lipid nanoparticle encapsulating immunostimulatory CpG oligodeoxynucleotides (SLNP@CpG) as a new immunotherapeutic modality that can reprogram TAMs and further bridge innate-to-adaptive immunity...

BACKGROUND: Intelligent hydrogels continue to encounter formidable obstacles in the field of cancer treatment. A wide variety of hydrogel materials have been designed for diverse purposes, but materials with satisfactory therapeutic effects are still urgently needed. METHODS: Here, we prepared an injectable hydrogel by means of physical crosslinking. Carbon nanoparticle suspension injection (CNSI), a sentinel lymph node imaging agent that has been widely used in the clinic, with sodium β-glycerophosphate (β-GP) were added to a temperature-sensitive chitosan (CS) hydrogel (CS/GP@CN) as an agent for photothermal therapy (PTT)...

Nanotheranostic agents combined the second near-infrared (NIR-II, 1000-1700 nm) fluorescence imaging with phototherapy strategy have attracted tremendous interest. However, the actual efficacy of NIR-II probes could be weakened by their limited accumulation and penetration in tumor tissues. Herein, a size-transformable NIR-II nanotheranostic agent (BBT-HASS@FPMPL NPs) is employed for simultaneously enhanced penetration and retention in deep tumor tissue to realize precise image and effective PTT therapy...

The dynamic nature of perfusion in living tissues, such as solid tumors during thermal therapy, produces challenging spatiotemporal thermal boundary conditions. Changes in perfusion can manifest as changes in convective heat transfer that influence temperature changes during cyclic heating. Herein, we propose a method to actively monitor changes in local convection (perfusion) in vivo by using a transient thermal pulsing analysis. Syngeneic 4T1 tumor cells were injected subcutaneously into BALB/c mice and followed by caliper measurements...

Thermal ablation is a crucial therapeutic modality for hepatocellular carcinoma (HCC), but its efficacy is often hindered by the high recurrence rate attributed to insufficient ablation. Furthermore, the residual tumors following insufficient ablation exhibit a more pronounced immunosuppressive state, which accelerates the disease progression and leads to immune checkpoint blockade (ICB) resistance. Herein, we present evidence that heightened intratumoral lactate accumulation, stemming from the augmented glycolytic activity of post-ablative residual HCC cells, may serve as a crucial driving force in exacerbating the immunosuppressive state of the tumor microenvironment (TME)...

Osteosarcoma is a malignant tumor with relatively high mortality rates in children and adolescents. While nanoparticles have been widely used in assisting the diagnosis and treatment of cancers, the biodistributions of nanoparticles in osteosarcoma models have not been well studied. Herein, we synthesize biocompatible and highly photoluminescent silicon quantum dot nanoparticles (SiQDNPs) and investigate their biodistributions in osteosarcoma mouse models after intravenous and intratumoral injections by fluorescence imaging...

PURPOSE/OBJECTIVE(S): NBTXR3 is a novel radioenhancer composed of functionalized hafnium oxide nanoparticles that are injected directly into the tumor. An ongoing phase I trial is assessing the application of NBTXR3 in the treatment of locally-advanced or borderline-resectable pancreatic ductal adenocarcinoma, with the primary goal of determining the recommended NBTXR3 dose for a subsequent phase II trial. Using patients from the ongoing phase I trial, we evaluated the spatial bio-distribution of NBTXR3 in the pancreas as function of time and assessed if there is migration of the compound during radiation therapy...

PURPOSE/OBJECTIVE(S): New approaches are needed for frail or elderly patients with locally advanced head and neck squamous cell carcinoma (LA HNSCC) who are unfit to receive cisplatin with concurrent radiotherapy (RT). NBTXR3 is a first-in-class radioenhancer, composed of functionalized hafnium oxide nanoparticles, administered by a single intratumoral (IT) injection and activated by RT. NBTXR3 locally amplifies the anti-tumoral response of RT without adding toxicity to surrounding healthy tissue as shown in a randomized trial in soft tissue sarcoma...

The lack of optimal models to evaluate novel agents is delaying the development of effective immunotherapies against human breast cancer (BC). In this prospective open label study, we applied neoadjuvant intratumoral immunotherapy with empty cowpea mosaic virus-like particles (eCPMV) to 11 companion dogs diagnosed with canine mammary cancer (CMC), a spontaneous tumor resembling human BC. We found that two neoadjuvant intratumoral eCPMV injections resulted in tumor reduction in injected tumors in all patients and in noninjected tumors located in the ipsilateral and contralateral mammary chains of injected dogs...

The development of an optimal treatment modality to improve the therapeutic outcome of breast cancer patients is still difficult. Poor antigen presentation to T cells is a major challenge in cancer immunotherapy. In this study, a synergistic immunotherapy strategy for breast cancer incorporating immune cell infiltration, immunogenic cell death (ICD), and dendritic cell (DC) maturation through a reactive oxygen species (ROS)-responsive dual-targeted smart nanosystem (anti-PD-L1-TKNP) for the simultaneous release of DOX, R848, and MIP-3α in the tumor microenvironment is reported...

Due to the high selectivity and non-invasive property, phototherapy has attracted increasing attention in the treatment of cancer. Targeted delivery and retention of photoactive agents in tumor tissue is of great significance and importance for safe and efficient phototherapy. Herein, we report a multifunctional nanomaterial photothermal agent, namely amino-modified graphene oxide (AGO) for anti-oral cancer photothermal therapy (PTT). Compared to the parental graphene oxide (GO) which has a negative charge and weak photothermal effect, AGO possesses a positive charge (∼+50 mV) and the significantly enhanced photothermal effect...

Localized expression of immunomodulatory molecules can stimulate immune responses against tumors in the tumor microenvironment while avoiding toxicities associated with systemic administration. In this study, we developed a polyethylenimine-modified porous silica nanoparticle (PPSN)-based delivery platform carrying cytokine mRNA for local immunotherapy in vivo . Our delivery platform was significantly more efficient than FDA-approved lipid nanoparticles for localized mRNA translation. We observed no off-target translation of mRNA in any organs and no evidence of systemic toxicity...

In the present article, we describe a multimodal radiobioconjugate that contains a chemotherapeutic agent (doxorubicin, DOX), a β-emitter (198 Au), and a guiding vector (trastuzumab, Tmab) for targeted therapy of cancers overexpressing HER2 receptors. To achieve this goal, radioactive gold nanoparticles (198 AuNPs) with a mean diameter of 30 nm were synthesized and coated with a poly(ethylene glycol) (PEG) linker conjugated to DOX and monoclonal antibody (Tmab) via peptide bond formation. In vitro experiments demonstrated a high affinity of the radiobioconjugate to HER2 receptors and cell internalization...

Chemotherapy has been widely used to treat cancer; however, the non-specific systemic toxicity of chemotherapeutic agents has always been an issue. Local injection treatment is a strategy used to reduce the undesired adverse effects of chemotherapeutic drugs. In addition, chemotherapeutic agents combined with thermotherapy are effective in further enhancing therapeutic potency. In the present study, we prepared an injectable hydrogel, namely, doxorubicin (DOX)-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticle (DPN) and magnetite nanoparticle (MNP) embedded in alginate hydrogel (DPN/MNP-HG), where DPN and MNP were the chemotherapeutic and heating agents, respectively, for intratumoral thermo-chemotherapy...

Cerium oxide nanoparticles (CeO2 NPs) have exceptional catalytic properties, rendering them highly effective in removing excessive reactive oxygen species (ROS) from biological environments, which is crucial in safeguarding these environments against radiation-induced damage. Additionally, the Ce atom's high Z number makes it an ideal candidate for utilisation as an X-ray imaging contrast agent. We herein show how the injection of albumin-stabilised 5 nm CeO2 NPs into mice revealed substantial enhancement in X-ray contrast, reaching up to a tenfold increase at significantly lower concentrations than commercial or other proposed contrast agents...

BACKGROUND: Nano-photothermal therapy (NPTT) has gained wide attention in cancer treatment due to its high efficiency and selective treatment strategy. The biggest challenges in the clinical application are the lack of (i) a reliable platform for mapping the thermal dose and (ii) efficient photothermal agents (PTAs). This study developed a 3D treatment planning for NPTT to reduce the uncertainty of treatment procedures, based on our synthesized nanohybrid. METHODS: This study aimed to develop a three-dimensional finite element method (FEM) model for in vivo NPTT in mice using magneto-plasmonic nanohybrids, which are complex assemblies of superparamagnetic iron oxide nanoparticles and gold nanorods...

As an alternative to classical brachytherapy, intratumoral injection of radionuclide-labeled nanoparticles (nanobrachytherapy, NBT) has been investigated as a superior delivery method over an intravenous route for radionuclide therapy of solid tumors. We created superparamagnetic iron oxide nanoparticles (SPIONs) coated with meso-1,2-dimercaptosuccinic acid (DMSA) and radiolabeled with Lutetium-177 (177 Lu), generating 177 Lu-DMSA@SPIONs as a potential antitumor agent for nanobrachytherapy. Efficient radiolabeling of DMSA@SPIONS by 177 Lu resulted in a stable bond with minimal leakage in vitro...

BACKGROUND/AIM: Synthetic miRNA inhibitors have recently attracted considerable interest as potential therapeutic agents for head and neck squamous cell carcinoma. However, due to the lack of evidence, no attempts have been made to deliver these inhibitors intravenously for squamous cell carcinoma. MATERIALS AND METHODS: This study investigated whether intravenous administration of a miR-21 inhibitor with lipid nanoparticles could suppress HNSCC in xenograft mice...

INTRODUCTION: Radiation therapy for head and neck squamous cell carcinoma is constrained by radiotoxicity to normal tissue. We demonstrate 100 nm theranostic nanoparticles for image-guided radiation therapy planning and enhancement in rat head and neck squamous cell carcinoma models. METHODS: PEG conjugated theranostic nanoparticles comprising of Au nanorods coated with Gadolinium oxide layers were tested for radiation therapy enhancement in 2D cultures of OSC-19-GFP-luc cells, and orthotopic tongue xenografts in male immunocompromised Salt sensitive or SS rats via both intratumoral and intravenous delivery...