Copper-Based Nanomedicines for Cuproptosis-Mediated Effective Cancer Treatment.

The recent discovery of cuproptosis, a novel copper-ion-induced cell death pathway, has suggested the novel therapeutic potential for treating heterogeneous and drug-resistant cancers. Currently, copper ionophore-based therapeutics have been designed to treat cancers, utilizing copper ions as a strategic tool to impede tumor proliferation and promote cellular demise. However, limitations of copper ionophore-based therapies include nontargeted delivery of copper ions, low tumor accumulation, and short half-life.

Applications of Cu-Loaded Silica Nanoparticles to Photothermal Therapy and Tumor-Specific Fluorescence Imaging.

Copper-based nanomaterials have been employed as therapeutic agents for cancer therapy and diagnosis. Nevertheless, persistent challenges, such as cellular toxicity, non-uniform sizes, and low photothermal efficiency, often constrain their applications. In this study, we present Cu-loaded silica nanoparticles fabricated through the chelation of Cu ions by silanol groups.

Applications of the Photocatalytic and Photoacoustic Properties of Gold Nanorods in Contrast-Enhanced Ultrasound and Photoacoustic Imaging.

The applications of ultrasound imaging are often limited due to low contrast, which arises from the comparable acoustic impedance of normal tissues and disease sites. To improve the low contrast, we propose a contrast agent called gas-generating laser-activatable nanorods for contrast enhancement (GLANCE), which enhances ultrasound imaging contrast in two ways. First, GLANCE absorbs near-infrared lasers and generates nitrogen gas bubbles through the photocatalytic function of gold nanorods and photolysis of azide compounds.

Mesenchymal Stem Cell-Mediated Deep Tumor Delivery of Gold Nanorod for Photothermal Therapy.

Gold nanoparticles (AuNPs) with various sizes and morphologies have been extensively investigated for effective photothermal therapy (PTT) against multiple cancer types. However, a highly dynamic and complex tumor microenvironment (TME) considerably reduces the efficacy of PTT by limiting deep tumor penetration of AuNPs. Herein, we propose a mesenchymal stem cell (MSC)-mediated deep tumor delivery of gold nanorod (AuNR) for a potent PTT.

Light-triggered photodynamic nanomedicines for overcoming localized therapeutic efficacy in cancer treatment.

Photodynamic nanomedicines have significantly enhanced the therapeutic efficacy of photosensitizers (PSs) by overcoming critical limitations of PSs such as poor water solubility and low tumor accumulation. Furthermore, functional photodynamic nanomedicines have enabled overcoming oxygen depletion during photodynamic therapy (PDT) and tissue light penetration limitation by supplying oxygen or upconverting light in targeted tumor tissues, resulting in providing the potential to overcome biological therapeutic barriers of PDT. Nevertheless, their localized therapeutic effects still remain a huddle for the effective treatment of metastatic- or recurrent tumors.

How Did Conventional Nanoparticle-Mediated Photothermal Therapy Become "Hot" in Combination with Cancer Immunotherapy?

One of the promising cancer treatment methods is photothermal therapy (PTT), which has achieved good therapeutic efficiency through nanoparticle-based photoabsorbers. Because of the various functions of nanoparticles, such as targeting properties, high light-to-heat conversion, and photostability, nanoparticle-mediated PTT successfully induces photothermal damage in tumor tissues with minimal side effects on surrounding healthy tissues. The therapeutic efficacy of PTT originates from cell membrane disruption, protein denaturation, and DNA damage by light-induced heat, but these biological impacts only influence localized tumor areas.

Tumor-activated carrier-free prodrug nanoparticles for targeted cancer Immunotherapy: Preclinical evidence for safe and effective drug delivery.

As immunogenic cell death (ICD) inducers initiating antitumor immune responses, certain chemotherapeutic drugs have shown considerable potential to reverse the immunosuppressive tumor microenvironment (ITM) into immune-responsive tumors. The application of these drugs in nanomedicine provides a more enhanced therapeutic index by improving unfavorable pharmacokinetic (PK) profiles and inefficient tumor targeting. However, the clinical translation of conventional nanoparticles is restricted by fundamental problems, such as risks of immunogenicity and potential toxicity by carrier materials, premature drug leakage in off-target sites during circulation, low drug loading contents, and complex structure and synthetic processes that hinder quality control (QC) and scale-up industrial production.

Thiol-Responsive Gold Nanodot Swarm with Glycol Chitosan for Photothermal Cancer Therapy.

Photothermal therapy (PTT) is one of the most promising cancer treatment methods because hyperthermal effects and immunogenic cell death via PTT are destructive to cancer. However, PTT requires photoabsorbers that absorb near-infrared (NIR) light with deeper penetration depth in the body and effectively convert light into heat. Gold nanoparticles have various unique properties which are suitable for photoabsorbers, e.

Rediscovery of nanoparticle-based therapeutics: boosting immunogenic cell death for potential application in cancer immunotherapy.

Immunogenic cell death (ICD) occurring by chemical and physical stimuli has shown the potential to activate an adaptive immune response in the immune-competent living body through the release of danger-associated molecular patterns (DAMPs) into the tumor microenvironment (TME). However, limitations to the long-term immune responses and systemic toxicity of conventional ICD inducers have led to unsatisfactory therapeutic efficacy in ICD-based cancer immunotherapy. Until now, various nanoparticle-based ICD-inducers have been developed to induce an antitumor immune response without severe toxicity, and to efficiently elicit an anticancer immune response against target cancer cells.

Tumor-Targeting Glycol Chitosan Nanoparticles for Cancer Heterogeneity.

Nanomedicine is extensively employed for cancer treatment owing to its unique advantages over conventional drugs and imaging agents. This increased attention to nanomedicine, however, has not fully translated into clinical utilization and patient benefits due to issues associated with reticuloendothelial system clearance, tumor heterogeneity, and complexity of the tumor microenvironment. To address these challenges, efforts are being made to modify the design of nanomedicines, including optimization of their physiochemical properties, active targeting, and response to stimuli, but these studies are often performed independently.

Recent Trends in Enzyme-Activatable Prodrugs for Targeted Cancer Therapy.

Enzyme-activatable anticancer prodrugs are modified medications that are composed of an anticancer drug, cleavable linker, and functional moiety. The purpose of such a prodrug structure is to generate multipurpose functions that traditional drugs cannot perform and to reduce the toxicity of conventional anticancer drugs by the mask of the cleavable linker. Once the cleavable linker is degraded via a specific chemical reaction in the cancer microenvironment, the cytotoxicity of the degraded prodrugs is selectively recovered.

Gas-generating nanoparticles for contrast-enhanced ultrasound imaging.

We present gas-generating solid nanoparticles as a new concept of an ultrasound contrast agent. The developed nanoparticles are sufficiently small (less than 100 nm in diameter) to escape vasculature and yet, upon external pulsed laser light activation, release nitrogen gas for enhanced contrast in ultrasound imaging. The gas-generating nanoconstructs combine the photocatalytic function of gold nanoparticles and photolysis of azide compounds.

Photoacoustic imaging of cancer cells with glycol-chitosan-coated gold nanoparticles as contrast agents.

Utility of glycol-chitosan-coated gold nanoparticles (GC-AuNPs) as a photoacoustic contrast agent for cancer cell imaging was demonstrated. Through the synergistic effect of glycol chitosan and gold nanoparticles, GC-AuNPs showed cellular uptake in breast cancer cells and resulted in strong photoacoustic signals in tissue-mimicking cell phantoms. The performance of GC-AuNPs as contrast agents was established with photoacoustic imaging and confirmed with dark-field microscopy.

Ultrasound-guided immunofunctional photoacoustic imaging for diagnosis of lymph node metastases.

Metastases, rather than primary tumors, determine mortality in the majority of cancer patients. A non-invasive immunofunctional imaging method was developed to detect sentinel lymph node (SLN) metastases using ultrasound-guided photoacoustic (USPA) imaging combined with glycol-chitosan-coated gold nanoparticles (GC-AuNPs) as an imaging contrast agent. GC-AuNPs, injected peritumorally into breast tumor-bearing mice, were taken up by immune cells, and subsequently transported to the SLN.

Direct Imaging of Cerebral Thromboemboli Using Computed Tomography and Fibrin-targeted Gold Nanoparticles.

Computed tomography (CT) is the current standard for time-critical decision-making in stroke patients, informing decisions on thrombolytic therapy with tissue plasminogen activator (tPA), which has a narrow therapeutic index. We aimed to develop a CT-based method to directly visualize cerebrovascular thrombi and guide thrombolytic therapy. Glycol-chitosan-coated gold nanoparticles (GC-AuNPs) were synthesized and conjugated to fibrin-targeting peptides, forming fib-GC-AuNP.

The effect of gold nanoparticle size on osteogenic differentiation of adipose-derived stem cells.

There have been many medical applications based on gold nanoparticles (GNPs) over the past several centuries. Recently, researchers have focused on bone tissue engineering applications utilizing GNPs. The effect of various sizes of gold nanoparticles on the differentiation of human adipose-derived stem cells (ADSCs) into osteoblasts was investigated.

Fluorescent dye labeled iron oxide/silica core/shell nanoparticle as a multimodal imaging probe.

Purpose: To develop an MRI/optical multimodal imaging probe based on dye-conjugated iron oxide/silica core/shell nanoparticle, and investigate the distance-dependent fluorescence quenching through careful control of the distance between the iron oxide core and fluorescent dyes.

Methods: Different size of core/shell nanoparticles were prepared by varying the silica shell width. PEGylation on the surface of silica shell was followed to improve the stability of particles in the physiological condition.

Biocompatible glycol chitosan-coated gold nanoparticles for tumor-targeting CT imaging.

Purpose: The application of gold nanoparticles (AuNPs) in biomedical field was limited due to the low stability in the biological condition. Herein, to enhance stability and tumor targeting ability of AuNPs, their surface was modified with biocompatible glycol chitosan (GC) and the in vivo biodistribution of GC coated AuNPs (GC-AuNPs) were studied through computed tomography (CT).

Methods: Polymer-coated gold nanoparticles were produced using GC as a reducing agent and a stabilizer.

Silica coated gold nanorods for imaging and photo-thermal therapy of cancer cells.

Due to their efficient conversion of absorbed light energy to heat gold nanorods have been proved to be an amazing tool for minimally invasive photo-thermal cancer therapy. The present in vitro study demonstrates the ability of silica coated Au nanorods to function as a dual probe for cancer-cell therapy and imaging without any toxic side-effects. HeLa cells were incubated with silica coated Au nanorods and imaged inside the cell just after 1 hour of incubation by a dark field set up due to strong surface enhanced Raman scattering.

Hyperacute direct thrombus imaging using computed tomography and gold nanoparticles.

Objective: Advancing the understanding and management of thromboembolic stroke requires simple and robust new methods that would be useful for the in vivo assessment of thrombus burden/distribution and for characterizing its evolution in a prompt and quantitative manner.

Methods: Animals (n=127) with experimental models of thrombosis were imaged with microcomputed tomography 5 minutes (and/or ~3 weeks) after intravenous injection of glycol chitosan (GC) gold nanoparticles (AuNPs).

Results: Nanoparticles accumulated in the thrombus, allowing computed tomography visualization of both the presence and extent of primary and recurrent thrombi in mouse carotid arteries without a single failure of detection.

Tumor-targeting multi-functional nanoparticles for theragnosis: new paradigm for cancer therapy.

Theragnostic nanoparticles (NPs) contain diagnostic and therapeutic functions in one integrated system, enabling diagnosis, therapy, and monitoring of therapeutic response at the same time. For diagnostic function, theragnostic NPs require the inclusion of noninvasive imaging modalities. Among them, optical imaging has various advantages including sensitivity, real-time and convenient use, and non-ionization safety, which make it the leading technique for theragnostic NPs.

Multifunctional nanoparticles for multimodal imaging and theragnosis.

Nanomedicine is the biomedical application of nanoscale materials for diagnosis and therapy of disease. Recent advances in nanotechnology and biotechnology have contributed to the development of multifunctional nanoparticles as representative nanomedicine. They were initially developed to enable the target-specific delivery of imaging or therapeutic agents for biomedical applications.