Theranostic Nanoparticles Research Articles

PEG-Polymer Encapsulated Aggregation-Induced Emission Nanoparticles for Tumor Theranostics.

In the field of tumor imaging and therapy, the aggregation-caused quenching (ACQ) effect of fluorescent dyes at high concentration is a great challenge. In this regard, the aggregation-induced emission luminogens (AIEgens) show great potential, since AIEgens effectively overcome the ACQ effect and have better fluorescence quantum yield, photobleaching resistance, and photosensitivity. Polyethylene glycol (PEG)-polymer is the most commonly used carrier to prepare nanoparticles (NPs). The advantage of PEGylation is that it can greatly prolong the metabolic half-life and reduce immunogenicity and toxicity. Considering that the hydrophobicity of most AIEgens hinders their application in organisms, the use of PEG-polymer encapsulation is an effective strategy to overcome this obstacle. Importantly, bioactive functional groups can be modified on PEG-polymers to enhance the biological effect of NPs. The combination of powerful AIEgens and PEG-polymers provides a new strategy for tumor imaging and therapy, which is promising for clinical application.

Low-Intensity Focused Ultrasound-Responsive Ferrite-Encapsulated Nanoparticles for Atherosclerotic Plaque Neovascularization Theranostics.

Pathological angiogenesis is a crucial factor that causes atherosclerotic plaque rupture. Sinoporphyrin sodium‐mediated sonodynamic therapy (DVDMS‐SDT) induces regression of plaque neovascularization in humans without causing obvious side effects. However, a clinical noninvasive theranostic strategy for atherosclerotic plaque neovascularization is urgently needed. A nanoplatform designed for multimodality imaging‐guided SDT in plaque angiogenesis theranostics, termed PFP–HMME@PLGA/MnFe2O4–ramucirumab nanoparticles (PHPMR NPs), is fabricated. It encapsulates manganese ferrite (MnFe2O4), hematoporphyrin monomethyl ether (HMME), and perfluoropentane (PFP) stabilized by polylactic acid‐glycolic acid (PLGA) shells and is conjugated to an anti‐VEGFR‐2 antibody. With excellent magnetic resonance imaging (MRI)/photoacoustic/ultrasound imaging ability, the distribution of PHPMR NPs in plaque can be observed in real time. Additionally, they actively accumulate in the mitochondria of rabbit aortic endothelial cells (RAECs), and the PHPMR NP‐mediated SDT promotes mitochondrial‐caspase apoptosis via the production of reactive oxygen species and inhibits the proliferation, migration, and tubulogenesis of RAECs. On day 3, PHPMR NP‐mediated SDT induces apoptosis in neovessel endothelial cells and improves hypoxia in the rabbit advanced plaque. On day 28, PHPMR NP‐mediated SDT reduces the density of neovessels, subsequently inhibiting intraplaque hemorrhage and inflammation and eventually stabilizing the plaque. Collectively, PHPMR NP‐mediated SDT presents a safe and effective theranostic strategy for inhibiting plaque angiogenesis.

Comprehensive review on ultrasound-responsive theranostic nanomaterials: mechanisms, structures and medical applications.

The field of theranostics has been rapidly growing in recent years and nanotechnology has played a major role in this growth. Nanomaterials can be constructed to respond to a variety of different stimuli which can be internal (enzyme activity, redox potential, pH changes, temperature changes) or external (light, heat, magnetic fields, ultrasound). Theranostic nanomaterials can respond by producing an imaging signal and/or a therapeutic effect, which frequently involves cell death. Since ultrasound (US) is already well established as a clinical imaging modality, it is attractive to combine it with rationally designed nanoparticles for theranostics. The mechanisms of US interactions include cavitation microbubbles (MBs), acoustic droplet vaporization, acoustic radiation force, localized thermal effects, reactive oxygen species generation, sonoluminescence, and sonoporation. These effects can result in the release of encapsulated drugs or genes at the site of interest as well as cell death and considerable image enhancement. The present review discusses US-responsive theranostic nanomaterials under the following categories: MBs, micelles, liposomes (conventional and echogenic), niosomes, nanoemulsions, polymeric nanoparticles, chitosan nanocapsules, dendrimers, hydrogels, nanogels, gold nanoparticles, titania nanostructures, carbon nanostructures, mesoporous silica nanoparticles, fuel-free nano/micromotors.

Element-specific contributions to improved magnetic heating of theranostic CoFe2O4 nanoparticles decorated with Pd

Decoration with Pd clusters increases the magnetic heating ability of cobalt ferrite (CFO) nanoparticles by a factor of two. The origin of this previous finding is unraveled by element-specific X-ray absorption spectroscopy (XAS) and magnetic circular dichroism (XMCD) combined with atomic multiplet simulations and density functional theory (DFT) calculations. While the comparison of XAS spectra with atomic multiplet simulations show that the inversion degree is not affected by Pd decoration and, thus, can be excluded as a reason for the improved heating performance, XMCD reveals two interrelated responsible sources: significantly larger Fe and Co magnetic moments verify an increased total magnetization which enhances the magnetic heating ability. This is accompanied by a remarkable change in the field-dependent magnetization particularly for Co ions which exhibit an increased low-field susceptibility and a reduced spin canting behavior in higher magnetic fields. Using DFT calculations, these findings are explained by reduced superexchange between ions on octahedral lattice sites via oxygen in close vicinity of Pd, which reinforces the dominating antiparallel superexchange interaction between ions on octahedral and tetrahedral lattice sites and thus reduces spin canting. The influence of the delocalized nature of Pd 4d electrons on the neighboring ions is discussed and the conclusions are illustrated with spin density isosurfaces of the involved ions. The presented results pave the way to design nanohybrids with tailored electronic structure and magnetic properties.

Theranostic Applications of Nanoparticle-Mediated Photoactivated Therapies

Nanoparticle-mediated light-activated therapies, such as photodynamic therapy and photothermal therapy, are earnestly being viewed as efficient interventional strategies against several cancer types. Theranostics is a key hallmark of cancer nanomedicine since it allows diagnosis and therapy of both primary and metastatic cancer using a single nanoprobe. Advanced in vivo diagnostic imaging using theranostic nanoparticles not only provides precise information about the location of tumor/s but also outlines the narrow time window corresponding to the maximum tumor-specific drug accumulation. Such information plays a critical role in guiding light-activated therapies with high spatio-temporal accuracy. Furthermore, theranostics facilitates monitoring the progression of therapy in real time. Herein, we provide a general review of the application of theranostic nanoparticles for in vivo image-guided light-activated therapy in cancer. The imaging modalities considered here include fluorescence imaging, photoacoustic imaging, thermal imaging, magnetic resonance imaging, X-ray computed tomography, positron emission tomography, and single-photon emission computed tomography. The review concludes with a brief discussion about the broad scope of theranostic light-activated nanomedicine.

Preclinical Cancer Theranostics—From Nanomaterials to Clinic: The Missing Link

AbstractNanomaterials with cancer‐imaging and therapeutic properties have emerged as the principal focus of nanotheranostics. The past decade has experienced a significant increase in research in the design, formulation, and preclinical and clinical trials of theranostic nanosystems. However, current theranostic nanoformulations have yet to be approved by the FDA for clinical use. Consequently, the present review focuses on the importance of the careful examination of the in vivo preclinical status of specific nanotheranostic materials as a prerequisite for their clinical translation. The scope of coverage is structured according to all of the major organic, inorganic, 2D, and hybrid nanotheranostic materials and their in vivo preclinical status. The therapeutic advantages and limitations of these materials in animal models are considered and the various strategies to enhance the biocompatibility of theranostic nanoparticles are summarized.

Abstract 307: Lymph node accumulation of theranostic lipid-based nanoparticles in healthy and diseased models: Preliminary results comparing nanoparticle morphology and targeting

Abstract Background: Accumulation of systemically administered nanoparticles (NPs) in lymph nodes has been exploited clinically for diagnostic imaging (e.g., USPIOs for lymph node metastasis) and therapeutic applications (e.g., vaccine delivery). However, the combination of diagnostic and therapeutic functionalities into a single theranostic NP has obliged undesirable trade-offs between either the imaging or drug delivery of the NP and their specific accumulation in lymph nodes. To overcome these trade-offs, we conducted a screen of various lipid-based theranostic NPs focusing on differing NP design and their resulting pharmacokinetic behaviours in healthy and diseased lymph node models. Methods: Lipid-based theranostic NPs with varying physicochemical characteristics (e.g., formulation, size and morphology, surface targeting, etc.) were prepared with positron emitting Cu-64 and administered systemically at equivalent NP doses in healthy and diseased rodent models (i.e., mice and rats). NP types were assessed for time-dependent accumulation in major lymph node basins via non-invasive whole-body PET/MR imaging at two or more timepoints per animal. 72-hours post-injection the animals were sacrificed, and lymph nodes and major organs were excised for gamma counting and pathological evaluation. Pharmacokinetic behaviour of NPs in healthy versus diseased lymph nodes were calculated in individual animals and in naïvely pooled datasets using non-compartmental analysis. Results: Preliminary analysis identified a leading NP candidate with specific lymph node targeting in healthy and diseased rodents: a discoidal, 35-nm peptide-targeted HDL-mimetic. In comparison with a spherical, 100-nm PEGylated NP, the discoidal NP obtained greater absolute (%ID) and relative (%ID/g) amounts of injected dose in anatomically matched lymph nodes than the spherical NP, regardless of lymph node pathology. At greatest measured concentration in healthy lymph nodes, typically 24-hpi, the differences between the discoidal and spherical NPs were on average 3-fold greater (2.893 vs. 0.864, %ID/g). Differences in other pharmacokinetic parameters such as AUC (%ID/g*h) and MRT (h) were equally pronounced. Conclusions: Our preliminary analysis uncovered a discoidal, peptide-targeted HDL-mimetic with remarkable accumulation in lymph nodes of healthy and diseased models. Future investigations will focus on the biochemical and cellular mechanisms underlying their unique lymphatic pharmacokinetics. These preliminary results provide key insights for design of theranostic NPs for non-invasive imaging and staging lymph node pathologies, and for applications in delivery of therapeutics to lymph nodes following systemic administration. Citation Format: Michael S. Valic, Mark Zheng, Lili Ding, Michelle Lai, Chris J. Zhang, Tina Ye, Jenny Ma, Michael Halim, Pamela Schimmer, Wenlei Jiang, Juan Chen, Gang Zheng. Lymph node accumulation of theranostic lipid-based nanoparticles in healthy and diseased models: Preliminary results comparing nanoparticle morphology and targeting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 307.

Complete ablation of tumors using synchronous chemoradiation with bimetallic theranostic nanoparticles

Synchronous chemotherapy and radiotherapy, termed chemoradiation therapy, is now an important standard regime for synergistic cancer treatment. For such treatment, nanoparticles can serve as improved carriers of chemotherapeutics into tumors and as better radiosensitizers for localized radiotherapy. Herein, we designed a Schottky-type theranostic heterostructure, Bi2S3–Au, with deep level defects (DLDs) in Bi2S3 as a nano-radiosensitizer and CT imaging contrast agent which can generate reactive free radicals to initiate DNA damage within tumor cells under X-ray irradiation. Methotrexate (MTX) was conjugated onto the Bi2S3–Au nanoparticles as a chemotherapeutic agent showing enzymatic stimuli-responsive release behavior. The designed hybrid system also contained curcumin (CUR), which cannot only serve as a nutritional supplement for chemotherapy, but also can play an important role in the radioprotection of normal cells. Impressively, this combined one-dose chemoradiation therapeutic injection of co-drug loaded bimetallic multifunctional theranostic nanoparticles with a one-time clinical X-ray irradiation, completely eradicated tumors in mice after approximately 20 days after irradiation showing extremely effective anticancer efficacy which should be further studied for numerous anti-cancer applications.

Development of mitochondrial targeted theranostic nanocarriers for treatment of gliomas

Theranostic nanoparticles were developed using synthesized Gadolinium doped iron oxide nanoplatforms by polyol process. Lenalidomide was coated on the magnetic core using PLGA by nanoprecipitation technique. Modification of Polyethylenimine was done with targeting moieties to provide targeting against gliomas. The cell line studies were performed on U87MG glioblastoma cell lines. Toxicity evaluation was done by mucosal toxicity study and hemolysis test. The magnetic core had ultra-small particle size of <10 nm and were paramagnetic with in vitro hyperthermia ability. The theranostic nanoparticles had high entrapment efficiency of 97.82 ± 0.425% and low particle size of 122.26 ± 2.17 nm. Cell line studies revealed the anti-cancer activity of formulation with localization in mitochondria. Toxicity studies on nasal mucosa and hemolysis test proved that the formulation was non-toxic as compared to positive control. Biodistribution studies on Wistar rats revealed the potential of the theranostic nanoparticles in brain targeting by intranasal route.

Recent Progress in Lipid Nanoparticles for Cancer Theranostics: Opportunity and Challenges.

Cancer is one of the major leading causes of mortality in the world. The implication of nanotherapeutics in cancer has garnered splendid attention owing to their capability to efficiently address various difficulties associated with conventional drug delivery systems such as non-specific biodistribution, poor efficacy, and the possibility of occurrence of multi-drug resistance. Amongst a plethora of nanocarriers for drugs, this review emphasized lipidic nanocarrier systems for delivering anticancer therapeutics because of their biocompatibility, safety, high drug loading and capability to simultaneously carrying imaging agent and ligands as well. Furthermore, to date, the lack of interaction between diagnosis and treatment has hampered the efforts of the nanotherapeutic approach alone to deal with cancer effectively. Therefore, a novel paradigm with concomitant imaging (with contrasting agents), targeting (with biomarkers), and anticancer agent being delivered in one lipidic nanocarrier system (as cancer theranostics) seems to be very promising in overcoming various hurdles in effective cancer treatment. The major obstacles that are supposed to be addressed by employing lipidic theranostic nanomedicine include nanomedicine reach to tumor cells, drug internalization in cancer cells for therapeutic intervention, off-site drug distribution, and uptake via the host immune system. A comprehensive account of recent research updates in the field of lipidic nanocarrier loaded with therapeutic and diagnostic agents is covered in the present article. Nevertheless, there are notable hurdles in the clinical translation of the lipidic theranostic nanomedicines, which are also highlighted in the present review along with plausible countermeasures.

Precise engineering of acorn-like Janus nanoparticles for cancer theranostics

The anisotropic Janus nanoparticles (JNPs) provide synergistic effects by concentrating multiple properties on a single carrier. Herein, we reported a novel and simple approach to fabricate acorn-like poly(acrylic acid)-mesoporous calcium phosphate/polydopamine (PAA-mCaP/PDA) JNPs, which were selectively functionalized with methoxy-poly(ethylene glycol)thiol (PEG-SH) on PDA domains to obtain superior stability, while the other mCaP sides served as a storage space and passage for the anti-cancer drug of doxorubicin (DOX). The unique acorn-like PAA-mCaP/PDA-PEG JNPs were utilized as novel theranostic agents for photoacoustic (PA) imaging-guided synergistic cancer chemo-phototherapy. More importantly, this synthetic strategy can be applied to synthesize various mesoporous Janus nanocarriers, paving the way toward designed synthesis of acorn-like JNPs in nanomedicine, biosensing and catalysis. Statement of significanceThe distinct acorn-like poly(acrylic acid)-mesoporous calcium phosphate/polydopamine Janus nanoparticles (PAA-mCaP/PDA JNPs) with a spherical-shaped PAA-mCaP core and PDA half-shell were fabricated for the first time. To achieve superior stability, the acorn-like PAA-mCaP/PDA JNPs were selectively functionalized with methoxy-poly(ethylene glycol)thiol (PEG-SH) on PDA domains to obtain acorn-like PAA-mCaP/PDA-PEG JNPs. The resultant acorn-like PAA-mCaP/PDA-PEG JNPs own an excellent biocompatibility, high drug-loading contents, good photothermal conversion efficiency, photoacoustic (PA) imaging capacity and pH/NIR dual-responsive properties, enabling the acorn-like JNPs to be applied for PA imaging-guided synergistic cancer chemo-phototherapy. More importantly, the synthetic approach could be extended to prepare acorn-like mesoporous inorganic substances/PDA JNPs for specific applications.

Low-dose X-ray enhanced tumor accumulation of theranostic nanoparticles for high-performance bimodal imaging-guided photothermal therapy

BackgroundTheranostic nanoparticles (NPs) have achieved rapid development owing to their capacity for personalized multimodal diagnostic imaging and antitumor therapy. However, the efficient delivery and bulk accumulation of NPs in tumors are still the decisive factors in improving therapeutic effect. It is urgent to seek other methods to alters tumor microenvironment (like vascular permeability and density) for enhancing the efficiency of nanoparticles delivery and accumulation at the tumor site.MethodsHerein, we developed a Raman-tagged hollow gold nanoparticle (termed as HAuNP@DTTC) with surface-enhanced Raman scattering (SERS) property, which could be accumulated efficiently in tumor site with the pre-irradiation of low-dose (3 Gy) X-ray and then exerted highly antitumor effect in breast cancer model.ResultsThe tumor growth inhibition (TGI) of HAuNP@DTTC-induced photothermal therapy (PTT) was increased from 60% for PTT only to 97%, and the lethal distant metastasis of 4T1 breast cancer (such as lung and liver) were effectively inhibited under the X-ray-assisted PTT treatment. Moreover, with the strong absorbance induced by localized surface plasmon resonance in near-infrared (NIR) region, the signals of Raman/photoacoustic (PA) imaging in tumor was also significantly enhanced after the administration of HAuNP@DTTC, indicating it could be used as the Raman/PA imaging and photothermal agent simultaneously under 808 nm laser irradiation.ConclusionsOur studied of the as-prepared HAuNP@DTTC integrated the Raman/PA imaging and PTT functions into the single platform, and showed the good prospects for clinical applications especially with the low-dose X-ray irradiation as an adjuvant, which will be a productive strategy for enhancing drug delivery and accumulation in tumor theranostics.Graphic

3D Spatial Distribution of Nanoparticles in Mice Brain Metastases by X-ray Phase-Contrast Tomography.

Characterizing nanoparticles (NPs) distribution in multiple and complex metastases is of fundamental relevance for the development of radiological protocols based on NPs administration. In the literature, there have been advances in monitoring NPs in tissues. However, the lack of 3D information is still an issue. X-ray phase-contrast tomography (XPCT) is a 3D label-free, non-invasive and multi-scale approach allowing imaging anatomical details with high spatial and contrast resolutions. Here an XPCT qualitative study on NPs distribution in a mouse brain model of melanoma metastases injected with gadolinium-based NPs for theranostics is presented. For the first time, XPCT images show the NPs uptake at micrometer resolution over the full brain. Our results revealed a heterogeneous distribution of the NPs inside the melanoma metastases, bridging the gap in spatial resolution between magnetic resonance imaging and histology. Our findings demonstrated that XPCT is a reliable technique for NPs detection and can be considered as an emerging method for the study of NPs distribution in organs.

Ultrasmall Porous Silica Nanoparticles with Enhanced Pharmacokinetics for Cancer Theranostics.

Theranostic nanoparticles hold the potential to greatly improve cancer management by providing personalized medicine. Although many theranostic nanoconstructs have been successful in preclinical studies, clinical translation is still hampered by their limited targeting capability and lack of successful therapeutic efficacy. We report the use of novel ultrasmall porous silica nanoparticles (UPSN) with enhanced in vivo pharmacokinetics such as high target tissue accumulation (12% ID/g in the tumor) and evasion from the reticuloendothelial system (RES) organs. Herein, UPSN is conjugated with the isotopic pair 90/86Y, enabling both noninvasive imaging as well as internal radiotherapy. In vivo PET imaging demonstrates prolonged blood circulation and excellent tumor contrast with 86Y-DOTA-UPSN. Tumor-to-muscle and tumor-to-liver uptake values were significantly high (12.4 ± 1.7 and 1.5 ± 0.5, respectively), unprecedented for inorganic nanomaterials. 90Y-DOTA-UPSN significantly inhibits tumor growth and increases overall survival, indicating the promise of UPSN for future clinical translation as a cancer theranostic agent.

Theranostic Mesoporous Silica Nanoparticles Loaded With a Curcumin-Naphthoquinone Conjugate for Potential Cancer Intervention.

A novel theranostic molecule, derived from curcumin (Cur) and naphthoquinone (NQ), allowing for cancer targeting, detection and treatment was previously described and termed CurNQ. To allow for enhanced theranostic capabilities, advanced drug delivery techniques are required. To this end, mesoporous silica nanoparticles (MSN) were synthesized and CurNQ was loaded into its pores to form the novel nanosystem MSN_CurNQ. The formation of the nanosystem aimed to augment the drug delivery of CurNQ through the EPR effect and sustained release. Moreover, the loading of CurNQ into its pores, formed a fluorescent nanoparticle that can be tracked, detected and visualized. Herein, the synthesis of a novel nanosystem is described and its theranostic potential are explored in vitro. MSN with an average size of 108 d.nm, a zeta potential of −42 mV and a PDI of 0.150 were synthesized and were impregnated with CurNQ to form the novel nanosystem MSN_CurNQ. MSN_CurNQ was demonstrated to have pH-responsivity whereby after 96 h, at pH 7.4, 31.5% of CurNQ was released from the MSN compared to 57% release at pH 6.8, corresponding to an increase of 25.5% in release with a 0.6 pH drop. The innate fluorescence was then characterized through confocal and fluorescence microscopy. Microscopy images illustrated the distinct, high intensity innate fluorescence with a high background to target ratio, thus confirming detection capabilities and potentially extending MSN_CurNQ’s application to molecular imaging purposes. Moreover, the chemotherapeutic potential of MSN_CurNQ was demonstrated as cell viability was reduced to below 50% in OVCAR-5, CACO-2, CHLA, and MCF-7 cell lines. Furthermore, MSN_CurNQ displayed tumor specific toxicity whereby the cell viability was reduced to a far greater extent in the cancer cell lines compared to a healthy fibroblast cell line (p = 0.000). Indeed, the novel MSN_CurNQ nanosystem has potential for applications in cancer targeting, detection and treatment.

Localized Delivery of Theranostic Nanoparticles and High-Energy Photons using Microneedles-on-Bioelectronics.

The low delivery efficiency of light-responsive theranostic nanoparticles (NPs) to target tumor sites, particularly to brain tumors due to the blood-brain barrier, has been a critical issue in NP-based cancer treatments. Furthermore, high-energy photons that can effectively activate theranostic NPs are hardly delivered to the target region due to the strong scattering of such photons while penetrating surrounding tissues. Here, a localized delivery method of theranostic NPs and high-energy photons to the target tumor using microneedles-on-bioelectronics is presented. Two types of microneedles and flexible bioelectronics are integrated and mounted on the edge of surgical forceps. Bioresorbable microneedles containing theranostic NPs deliver the NPs into target tumors (e.g., glioblastoma, pituitary adenoma). Magnetic resonance imaging can locate the NPs. Then, light-guiding/spreading microneedles deliver high-energy photons from bioelectronics to the NPs. The high-energy photons activate the NPs to treat tumor tissues by photodynamic therapy and chemotherapy. The controlled thermal actuation by the bioelectronics accelerates the diffusion of chemo-drugs. The proposed method is demonstrated with mouse tumor models in vivo.

Imaging‐Guided Targeted Drug Delivery using Stimuli‐Sensitive Theranostic Nanoparticles: Characterization and In Vivo Trafficking Patterns

Purpose : In type 1 diabetes (T1D), the existing delivery systems for insulin all suffer from the inability to regulate insulin without patient intervention. A major unmet medical need is to develop innovative strategy, which would increase the efficacy of immune therapeutics but also, reduce their toxicity. Targeted drug carriers using polymeric nanoparticles (NP) holds particular promise to enhance the delivery of immunoregulatory agents to treat T1D. The aim of this study was to synthesize and characterize the in vivo trafficking patterns of stimuli-responsive, thermosensitive, immunoregulatory-carriers for potential use in image-guided targeted delivery and on site controlled release. Methods : A number of metal nanoparticles with hyperthermia magnetic (HMNs) properties made out of Gd-Zn-Fe were fabricated that intrinsically have the ability to self-regulate their heating level to the desired therapeutic range, Curie temperature (Tc). Production of particles of uniform size and shape was ensured by constant reaction kinetics and efficient physical and chemical reactions in solution. The particles morphology was examined using electron microscopy. The size distribution was evaluated using Malvern Nanosizer device. Magnetic resonance imaging (MRI) relaxivities of HMNs were measured over a range of 25-45°C. Non-targeted and MECA79-targeted HMNs were engineered using self-assembly nanoprecipitation method. Targeted trafficking of MECA79-HMNs in skin transplanted NOD mice with distinctive lymphatic draining to the draining lymph nodes (DLN) was evaluated. To be able to image the particles, particles were coated with IRDye 800CW. Using iBox, live fluorescence imaging was carried out 8 days post transplantation (24 hours post IV administration). Results : The temperature of HMN (with Tc 38-40°C) rose only up to the Tc when the particles were subjected to an oscillating magnetic field, and further increasing the intensity of the field did not increase heating beyond their Tc. Increasing Gd ratio modulated Tc linearly with amount of Gd-substituted Zn Ferrite particles (Figure 1A). NPs TEM micrograph showed a dispersion of spherical particles with a narrow size distribution (Figure 1B). MRI relaxivities, R1 and R2, showed linear increase of the relaxation rate. Twenty-four hours post IV administration, there was a significant increase in the trafficking of MECA79 conjugated particles as compared to the non-targeted NPs to the DLN in the skin transplanted NOD mice (Figure 2). Conclusion : Nanomedicine's application of ITS to T1D remains to be developed. While there are a number of delivery approaches that target the LN, virtually all of them rely on passive lymphatic absorption (i.e., intradermal injection). Data presented here represent major achievements to establish for the first time systemic delivery of particles to specific sites in diabetic mice. These experiments serve the basis for developing more of multifunctional NPs.

The cancer therapy materialization by theranostic nanoparticles based on gold doped iron oxide under electromagnetic field amplification

The harnessing of the cancer X-ray radiation therapy by gold-decorated Fe3O4 theranostic nanoparticles (Au-Fe3O4 NPs) under electromagnetic field was articulated. The applied electromagnetic field could assemble the NPs inside cell in oriented field direction and enhance the local irradiation dose inside cell. By materializing NPs, the absorption of the energy exposed by X-ray radiation under electromagnetic field was restricted. The cytotoxic properties of the Au-Fe3O4 NPs were assessed using MTT assay in L929, HeLa and PC3 cell lines under radiation and dark conditions. The efficiency of the Au-Fe3O4 NPs under 2 Gy dose radiations was higher than 6 Gy radiations in untreated cells. The in vitro measurements showed that under electromagnetic field and X-ray radiation therapy with Au-Fe3O4 NPs, around 90% of the cancer cells population was annihilated. The in vivo measurements indicated that the tumor shape and size under X-ray with Au-Fe3O4 NPs after 3 weeks were efficiently deteriorated.

Tailored theranostic nanoparticles cause efficient ferroptosis in head and neck squamous cell carcinoma through a reactive oxygen species “butterfly effect”

Multidrug resistance (MDR) is the main reason of chemotherapy failure in head and neck squamous cell carcinoma (HNSCC) patients, leading to the worst outcome. Recently, ferroptosis shows great potential in cancer therapy via abnormal intracellular ROS accumulation, which may bypass the MDR effect of HNSCC. Herein, SNP and DHA, which is a ferroptosis inducer, were loaded to nanoparticles of zeolite imidazolate framework (Zif-8) with surface-immobilized FA to achieve a synergist effect and target FR-overexpressing HNSCC cells through ferroptosis. As the donor of Fe2+ and nitric oxide (NO), SNP triggers DHA-Fe2+ reaction on one hand and NO correlative tumor inhibition on the other, which leads to intracellular formation of ROS. Loading capacity of the nanoparticles (NPs) reached 45.7% (DHA) and 13.8% (SNP) respectively. Once internalized, the pH-sensitive Zif-8 degraded in lysosomes and the drugs were released. In vitro study showed that the intracellular ROS level of cancer cell was greatly enhanced. Meanwhile, the cell viability decreased sharply to 15%. Apart from extra ROS formation, key antioxidants, including glutathione (GSH) and glutathione peroxidase 4 (GPX4), were also found inhibited. In vivo experiments demonstrated that the tumor inhibition rate of DHA/SNP@Zif-8-FA reached 66.93%. On the other hand, indocyanine green (ICG) was loaded in our nanoreactor so that the tumor could be tracked and visualized by both fluorescent and photoacoustic instruments. Above all, these remarkable features of ICG loaded DHA/SNP@Zif-8-FA (DHA/SNP/ICG@Zif-8-FA) may help in the development of more diagnostic and therapeutic treatments for HNSCC.

Drug Resistance in Metastatic Breast Cancer: Tumor Targeted Nanomedicine to the Rescue.

Breast cancer, specifically metastatic breast, is a leading cause of morbidity and mortality in women. This is mainly due to relapse and reoccurrence of tumor. The primary reason for cancer relapse is the development of multidrug resistance (MDR) hampering the treatment and prognosis. MDR can occur due to a multitude of molecular events, including increased expression of efflux transporters such as P-gp, BCRP, or MRP1; epithelial to mesenchymal transition; and resistance development in breast cancer stem cells. Excessive dose dumping in chemotherapy can cause intrinsic anti-cancer MDR to appear prior to chemotherapy and after the treatment. Hence, novel targeted nanomedicines encapsulating chemotherapeutics and gene therapy products may assist to overcome cancer drug resistance. Targeted nanomedicines offer innovative strategies to overcome the limitations of conventional chemotherapy while permitting enhanced selectivity to cancer cells. Targeted nanotheranostics permit targeted drug release, precise breast cancer diagnosis, and importantly, the ability to overcome MDR. The article discusses various nanomedicines designed to selectively target breast cancer, triple negative breast cancer, and breast cancer stem cells. In addition, the review discusses recent approaches, including combination nanoparticles (NPs), theranostic NPs, and stimuli sensitive or “smart” NPs. Recent innovations in microRNA NPs and personalized medicine NPs are also discussed. Future perspective research for complex targeted and multi-stage responsive nanomedicines for metastatic breast cancer is discussed.