Mechanisms and Barriers in Nanomedicine: Progress in the Field and Future Directions.

In recent years, steady progress has been made in synthesizing and characterizing engineered nanoparticles, resulting in several approved drugs and multiple promising candidates in clinical trials. Regulatory agencies such as the Food and Drug Administration and the European Medicines Agency released important guidance documents facilitating nanoparticle-based drug product development, particularly in the context of liposomes and lipid-based carriers. Even with the progress achieved, it is clear that many barriers must still be overcome to accelerate translation into the clinic. At the recent conference workshop "Mechanisms and Barriers in Nanomedicine" in May 2023 in Colorado, U.S.A., leading experts discussed the formulation, physiological, immunological, regulatory, clinical, and educational barriers. This position paper invites open, unrestricted, nonproprietary discussion among senior faculty, young investigators, and students to trigger ideas and concepts to move the field forward.

Small Extracellular Vesicles From Infarcted and Failing Heart Accelerate Tumor Growth.

BACKGROUND: Myocardial infarction (MI) and heart failure are associated with an increased incidence of cancer. However, the mechanism is complex and unclear. Here, we aimed to test our hypothesis that cardiac small extracellular vesicles (sEVs), particularly cardiac mesenchymal stromal cell-derived sEVs (cMSC-sEVs), contribute to the link between post-MI left ventricular dysfunction (LVD) and cancer. METHODS: We purified and characterized sEVs from post-MI hearts and cultured cMSCs. Then, we analyzed cMSC-EV cargo and proneoplastic effects on several lines of cancer cells, macrophages, and endothelial cells. Next, we modeled heterotopic and orthotopic lung and breast cancer tumors in mice with post-MI LVD. We transferred cMSC-sEVs to assess sEV biodistribution and its effect on tumor growth. Finally, we tested the effects of sEV depletion and spironolactone treatment on cMSC-EV release and tumor growth. RESULTS: Post-MI hearts, particularly cMSCs, produced more sEVs with proneoplastic cargo than nonfailing hearts did. Proteomic analysis revealed unique protein profiles and higher quantities of tumor-promoting cytokines, proteins, and microRNAs in cMSC-sEVs from post-MI hearts. The proneoplastic effects of cMSC-sEVs varied with different types of cancer, with lung and colon cancers being more affected than melanoma and breast cancer cell lines. Post-MI cMSC-sEVs also activated resting macrophages into proangiogenic and protumorigenic states in vitro. At 28-day follow-up, mice with post-MI LVD developed larger heterotopic and orthotopic lung tumors than did sham-MI mice. Adoptive transfer of cMSC-sEVs from post-MI hearts accelerated the growth of heterotopic and orthotopic lung tumors, and biodistribution analysis revealed accumulating cMSC-sEVs in tumor cells along with accelerated tumor cell proliferation. sEV depletion reduced the tumor-promoting effects of MI, and adoptive transfer of cMSC-sEVs from post-MI hearts partially restored these effects. Finally, spironolactone treatment reduced the number of cMSC-sEVs and suppressed tumor growth during post-MI LVD. CONCLUSIONS: Cardiac sEVs, specifically cMSC-sEVs from post-MI hearts, carry multiple protumorigenic factors. Uptake of cMSC-sEVs by cancer cells accelerates tumor growth. Treatment with spironolactone significantly reduces accelerated tumor growth after MI. Our results provide new insight into the mechanism connecting post-MI LVD to cancer and propose a translational option to mitigate this deadly association.

Antibody Delivery into the Brain by Radiosensitizer Nanoparticles for Targeted Glioblastoma Therapy.

Background: Glioblastoma is the most lethal primary brain malignancy in adults. Standard of care treatment, consisting of temozolomide (TMZ) and adjuvant radiotherapy (RT), mostly does not prevent local recurrence. The inability of drugs to enter the brain, in particular antibody-based drugs and radiosensitizers, is a crucial limitation to effective glioblastoma therapy. Methods: Here, we developed a combined strategy using radiosensitizer gold nanoparticles coated with insulin to cross the blood-brain barrier and shuttle tumor-targeting antibodies (cetuximab) into the brain. Results: Following intravenous injection to an orthotopic glioblastoma mouse model, the nanoparticles specifically accumulated within the tumor. Combining targeted nanoparticle injection with TMZ and RT standard of care significantly inhibited tumor growth and extended survival, as compared to standard of care alone. Histological analysis of tumors showed that the combined treatment eradicated tumor cells, and decreased tumor vascularization, proliferation, and repair. Conclusions: Our findings demonstrate radiosensitizer nanoparticles that effectively deliver antibodies into the brain, target the tumor, and effectively improve standard of care treatment outcome in glioblastoma.

Multifunctional nanoprobe for real-time in vivo monitoring of T cell activation.

Genetically engineered T cells are a powerful new modality for cancer immunotherapy. However, their clinical application for solid tumors is challenging, and crucial knowledge on cell functionality in vivo is lacking. Here, we fabricated a nanoprobe composed of dendrimers incorporating a calcium sensor and gold nanoparticles, for dual-modal monitoring of engineered T cells within a solid tumor. T cells engineered to express a melanoma-specific T-cell receptor and loaded with the nanoprobe were longitudinally monitored within melanoma xenografts in mice. Fluorescent imaging of the nanoprobe's calcium sensor revealed increased intra-tumoral activation of the T cells over time, up to 24 h. Computed tomography imaging of the nanoprobe's gold nanoparticles revealed the cells' intra-tumoral distribution pattern. Quantitative analysis revealed the intra-tumoral T cell quantities. Thus, this nanoprobe reveals intra-tumoral persistence, penetration and functional status of genetically engineered T cells, which can advance T cell-based immunotherapy and promote next-generation live cell imaging.

Photothermal Therapy with HER2-Targeted Silver Nanoparticles Leading to Cancer Remission.

Nanoparticles exhibiting the localized surface plasmon resonance (LSPR) phenomenon are promising tools for diagnostics and cancer treatment. Among widely used metal nanoparticles, silver nanoparticles (Ag NPs) possess the strongest light scattering and surface plasmon strength. However, the therapeutic potential of Ag NPs has until now been underestimated. Here we show targeted photothermal therapy of solid tumors with 35 nm HER2-targeted Ag NPs, which were produced by the green synthesis using an aqueous extract of Lavandula angustifolia Mill. Light irradiation tests demonstrated effective hyperthermic properties of these NPs, namely heating by 10 °C in 10 min. To mediate targeted cancer therapy, Ag NPs were conjugated to the scaffold polypeptide, affibody ZHER2:342, which recognizes a clinically relevant oncomarker HER2. The conjugation was mediated by the PEG linker to obtain Ag-PEG-HER2 nanoparticles. Flow cytometry tests showed that Ag-PEG-HER2 particles successfully bind to HER2-overexpressing cells with a specificity comparable to that of full-size anti-HER2 IgGs. A confocal microscopy study showed efficient internalization of Ag-PEG-HER2 into cells in less than 2 h of incubation. Cytotoxicity assays demonstrated effective cell death upon exposure to Ag-PEG-HER2 and irradiation, caused by the production of reactive oxygen species. Xenograft tumor therapy with Ag-PEG-HER2 particles in vivo resulted in full primary tumor regression and the prevention of metastatic spread. Thus, for the first time, we have shown that HER2-directed plasmonic Ag nanoparticles are effective sensitizers for targeted photothermal oncotherapy.

CT and MRI Imaging of Theranostic Bimodal Fe3O4@Au NanoParticles in Tumor Bearing Mice.

Gold-containing nanoparticles are proven to be an effective radiosensitizer in the radiotherapy of tumors. Reliable imaging of nanoparticles in a tumor and surrounding normal tissues is crucial both for diagnostics and for nanoparticle application as radiosensitizers. The Fe3O4 core was introduced into gold nanoparticles to form a core/shell structure suitable for MRI imaging. The aim of this study was to assess the in vivo bimodal CT and MRI enhancement ability of novel core/shell Fe3O4@Au theranostic nanoparticles. Core/shell Fe3O4@Au nanoparticles were synthesized and coated with PEG and glucose. C57Bl/6 mice bearing Ca755 mammary adenocarcinoma tumors received intravenous injections of the nanoparticles. CT and MRI were performed at several timepoints between 5 and 102 min, and on day 17 post-injection. Core/shell Fe3O4@Au nanoparticles provided significant enhancement of the tumor and tumor blood vessels. Nanoparticles also accumulated in the liver and spleen and were retained in these organs for 17 days. Mice did not show any signs of toxicity over the study duration. These results indicate that theranostic bimodal Fe3O4@Au nanoparticles are non-toxic and serve as effective contrast agents both for CT and MRI diagnostics. These nanoparticles have potential for future biomedical applications in cancer diagnostics and beyond.

Noninvasive Tracking of Natural Killer Cells Using Gold Nanoparticles.

Natural killer (NK)-cell-based immunotherapy is emerging as an attractive approach for cancer treatment. However, to facilitate and expedite clinical implementation, important questions must be answered regarding the in vivo functionality and trafficking patterns of the transferred cells. We have recently developed a noninvasive cell-tracking technique, based on gold nanoparticles (GNPs) as cell-labeling and contrast agents for whole-body computed tomography (CT) imaging. Herein, we report the implementation of this technique for longitudinal and quantitative tracking of NK cell kinetics, the migration and biodistribution in tumor-bearing mice. NK cells were successfully labeled with GNPs, without impairing their biological function, as assessed both in vitro, by cytokine release and cytotoxicity assays, and in vivo, using a xenograft model of human tumors. Using CT, we longitudinally tracked the migration of intravenously injected NK cells and observed an accumulation of effector cell clusters at the tumor site, up to 72 h. Fluorescence imaging of the cells over time correlated with ex vivo quantitative analysis of gold content in the tumor, validating the accuracy and reliability of our technique. Our cell-tracking approach thus offers a valuable tool for preclinical studies, as well as for clinical applications, to elucidate the fate of NK cells and promote the implementation of NK-cell-based immunotherapy.

'Golden' exosomes as delivery vehicles to target tumors and overcome intratumoral barriers: in vivo tracking in a model for head and neck cancer.

Exosomes are promising vectors for anti-tumor therapy, due to their biocompatibility, low immunogenicity, and innate ability to interact with target cells. However, promoting clinical application of exosome-based therapeutics requires elucidation of key issues, including exosome biodistribution, tumor targeting and accumulation, and the ability to overcome tumor barriers that limit the penetration of various nano-carriers and drugs. Here, we examined these parameters in exosomes derived from mesenchymal stem cells (MSC-exo) and from the A431 squamous cell carcinoma line (A431-exo), which both have potential use in cancer therapy. Using our novel technique combining gold nanoparticle (GNP) labeling of exosomes and non-invasive computed tomography imaging (CT), we longitudinally and quantitatively tracked the two intravenously-injected exosome types in A431 tumor-bearing mice. CT imaging up to 48 h and subsequent ex vivo analysis revealed tumor homing abilities of both exosome types, yet there was significantly higher tumor accumulation of MSC-exo as compared to A431-exo. Moreover, MSC-exo demonstrated the ability to penetrate the tumor and distribute throughout its bulk, while non-encapsulated GNPs remained concentrated at the tumor periphery. Histological analysis showed penetration of MSC-exo not only into the tumor tissue, but also into tumor cell cytoplasm. While the proportion of biodistribution between organs at 48 h was similar for both exosome types, more rapid clearance was indicated for A431-exo. Thus, our findings demonstrate an effect of exosome type on tumor targeting abilities and biodistribution, and suggest that MSC-exo may have superior abilities for tumor-targeted therapy.

Glucose-Functionalized Liposomes for Reducing False Positives in Cancer Diagnosis.

Fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) is a powerful tool for cancer detection, staging, and follow-up. However, 18F-FDG-PET imaging has high rates of false positives, as it cannot distinguish between tumor and inflammation regions that both feature increased glucose metabolic activity. In the present study, we engineered liposomes coated with glucose and the chelator dodecane tetraacetic acid (DOTA) complexed with copper, to serve as a diagnostic technology for differentiating between cancer and inflammation. This liposome technology is based on FDA-approved materials and enables complexation with metal cations and radionuclides. We found that these liposomes were preferentially uptaken by cancer cell lines with high metabolic activity, mediated via glucose transporter-1. In vivo, these liposomes were avidly uptaken by tumors, as compared to liposomes without glucose coating. Moreover, in a combined tumor-inflammation mouse model, these liposomes accumulated in the tumor tissue and not in the inflammation region. Thus, this technology shows high specificity for tumors while evading inflammation and has potential for rapid translation to the clinic and integration with existing PET imaging systems, for effective reduction of false positives in cancer diagnosis.

Construction of Enzyme Nanoreactors to Enable Tumor Microenvironment Modulation and Enhanced Cancer Treatment.

Enzymes play pivotal roles in regulating and maintaining the normal functions of all living systems, and some of them are extensively employed for diagnosis and treatment of diverse diseases. More recently, several kinds of enzymes with unique catalytic activities have been found to be promising options to directly suppress tumor growth and/or augment the therapeutic efficacy of other treatments by modulating the hostile tumor microenvironment (TME), which is reported to negatively impair the therapeutic efficacy of different cancer treatments. In this review, first a summary is presented on the chemical approaches utilized for the construction of distinct enzyme nanoreactors with well-retained catalytic performance and reduced immunogenicity. Then, the utilization of such enzyme nanoreactors in attenuating tumor hypoxia, modulating extracellular matrix, and amplifying tumor oxidative stress is discussed in depth. Afterward, some perspectives are presented on the future development of such enzyme nanoreactors in TME modulation and enhanced cancer treatment.

Nanomedicine to target multidrug resistant tumors.

Nanomedicine employs nanotechnologies to develop innovative applications, and more specifically nano-objects in the field of human health, through exploitation of the physical, chemical and biological properties of materials at the nanoscale. The use of nanovehicles capable of transporting and releasing the active therapeutic payload into target cells, particularly in the case of cancer or inflammatory diseases, can also enhance diagnosis. Therefore, nanomedicines improve the benefit/risk ratio of drugs by increasing their bioavailability, selectivity, and efficacy in the target tissue, while reducing the necessary doses and hence diminishing untoward toxicity to healthy tissues. Overcoming multidrug resistance (MDR) to antitumor agents is a central goal of cancer research and therapeutics, making it possible to treat these diseases more accurately and effectively. The adaptability of nanomedicines e.g. modulation of their components, surface functionalization, encapsulation of various active therapeutics as well as the possibility of combining several treatments using a single nanoparticle platform, are characteristics which are perfectly poised to address classical chemoresistance, a major obstacle towards curative cancer therapy. In this review, we discuss an assortment of nanomedicines along with those that should be developed in order to surmount cancer MDR; these include exosomes, natural compounds, lipid nanocapsules, prodrug self-assemblies, and gold nanoparticles.

Nanoparticle contrast agents for X-ray imaging applications.

X-ray imaging is the most widely used diagnostic imaging method in modern medicine and several advanced forms of this technology have recently emerged. Iodinated molecules and barium sulfate suspensions are clinically approved X-ray contrast agents and are widely used. However, these existing contrast agents provide limited information, are suboptimal for new X-ray imaging techniques and are developing safety concerns. Thus, over the past 15 years, there has been a rapid growth in the development of nanoparticles as X-ray contrast agents. Nanoparticles have several desirable features such as high contrast payloads, the potential for long circulation times, and tunable physicochemical properties. Nanoparticles have also been used in a range of biomedical applications such as disease treatment, targeted imaging, and cell tracking. In this review, we discuss the principles behind X-ray contrast generation and introduce new types of X-ray imaging modalities, as well as potential elements and chemical compositions that are suitable for novel contrast agent development. We focus on the progress in nanoparticle X-ray contrast agents developed to be renally clearable, long circulating, theranostic, targeted, or for cell tracking. We feature agents that are used in conjunction with the newly developed multi-energy computed tomography and mammographic imaging technologies. Finally, we offer perspectives on current limitations and emerging research topics as well as expectations for the future development of the field. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Multifunctional Dendrimer-Entrapped Gold Nanoparticles for Labeling and Tracking T Cells Via Dual-Modal Computed Tomography and Fluorescence Imaging.

Nanosystems for monitoring and tracking T cells provide an important basis for evaluating the functionality and efficacy of T cell-based immunotherapy. To this end, we designed herein an efficient nanoprobe for T cell monitoring and tracking using poly(amidoamine) (PAMAM) dendrimer-entrapped gold nanoparticles (Au DENPs) conjugated with Fluo-4 for dual-mode computed tomography (CT) and fluorescence imaging. In this study, PAMAM dendrimers of generation 5 (G5) were modified with hydroxyl-terminated polyethylene glycol (PEG) and then used to entrap 2.0 nm Au NPs followed by acetylation of the excess amine groups on the dendrimer surface. Subsequently, the calcium ion probe was covalently attached to the dendrimer nanohybrids through the PEG hydroxyl end groups to gain the functional {(Au0)25-G5.NHAc-(PEG)14-(Fluo-4)2} nanoprobe. This nanoprobe had excellent water solubility, high X-ray attenuation coefficient, and good cytocompatibility in the given concentration range, as well as a high T cell labeling efficiency. Confocal microscopy and flow cytometry results demonstrated that the nanoprobe was able to fluorescently sense activated T cells. Moreover, the nanoprobe was able to realize both CT and fluorescence imaging of subcutaneously injected T cells in vivo. Thus, the developed novel dendrimer-based nanosystem may hold great promise for advancing and improving the clinical application of T cell-based immunotherapy.

Magnetic Targeting of mTHPC To Improve the Selectivity and Efficiency of Photodynamic Therapy.

Photodynamic therapy (PDT) is a promising recognized treatment for cancer. To date, PDT drugs are injected systemically, and the tumor area is irradiated to induce cell death. Current clinical protocols have several drawbacks, including limited accessibility to solid tumors and insufficient selectivity of drugs. Herein, we propose an alternative approach to improve PDT effectiveness by magnetic targeting of responsive carriers conjugated to the PDT drug. We coordinatively attached a meso-tetrahydroxyphenylchlorin (mTHPC) photosensitizer to Ce-doped-γ-Fe2O3 maghemite nanoparticles (MNPs). These MNPs are superparamagnetic and biocompatible, and the resulting mTHPC-MNPs nanocomposites are stable in aqueous suspensions. MDA-MB231 (human breast cancer) cells incubated with the mTHPC-MNPs showed high uptake and high death rates in cell population after PDT. The exposure to external magnetic forces during the incubation period directed the nanocomposites to selected sites enhancing drug accumulation that was double that of cells with no magnetic exposure. Next, breast cancer tumors were induced subcutaneously in mice and treated magnetically. In vivo results showed accelerated drug accumulation in tumors of mice injected with mTHPC-MNP nanocomposites, compared to the free drug. PDT irradiation led to a decrease in tumor size of both groups, whereas treatment with the focused magnetic nanocomposites led to significant tumor regression. Our results demonstrate a method to improve the current PDT treatments by applying magnetic forces to effectively direct the drug to cancerous tissue. This approach leads to a highly localized and effective PDT process, opening new directions for clinical PDT protocols.

Intranasal Delivery of Mesenchymal Stem Cell Derived Exosomes Loaded with Phosphatase and Tensin Homolog siRNA Repairs Complete Spinal Cord Injury.

Individuals with spinal cord injury (SCI) usually suffer from permanent neurological deficits, while spontaneous recovery and therapeutic efficacy are limited. Here, we demonstrate that when given intranasally, exosomes derived from mesenchymal stem cells (MSC-Exo) could pass the blood brain barrier and migrate to the injured spinal cord area. Furthermore, MSC-Exo loaded with phosphatase and tensin homolog small interfering RNA (ExoPTEN) could attenuate the expression of PTEN in the injured spinal cord region following intranasal administrations. In addition, the loaded MSC-Exo considerably enhanced axonal growth and neovascularization, while reducing microgliosis and astrogliosis. The intranasal ExoPTEN therapy could also partly improve structural and electrophysiological function and, most importantly, significantly elicited functional recovery in rats with complete SCI. The results imply that intranasal ExoPTEN may be used clinically to promote recovery for SCI individuals.

Ultrasmall Oxygen-Deficient Bimetallic Oxide MnWOX Nanoparticles for Depletion of Endogenous GSH and Enhanced Sonodynamic Cancer Therapy.

Sonodynamic therapy (SDT) triggered by ultrasound (US) has attracted increasing attention owing to its abilities to overcome critical limitations including low tissue-penetration depth and phototoxicity in photodynamic therapy. Herein, the design of a new type of sonosensitizer is revealed, namely, ultrasmall oxygen-deficient bimetallic oxide MnWOX nanoparticles, for multimodal imaging-guided enhanced SDT against cancer. As-made MnWOX nanoparticles with poly(ethylene glycol) (PEG) modification show high physiological stability and biocompatibility. Interestingly, such MnWOX -PEG nanoparticles exhibit highly efficient US-triggered production of 1 O2 and •OH, higher than that of previously reported sonosensitizers (e.g., protoporphyrin IX and titanium dioxide), because the oxygen-deficient structure of MnWOX serves as an electron trap site to prevent electron-hole recombination. The glutathione depletion capability of MnWOX -PEG can also further favor SDT-triggered cancer cell killing. With efficient tumor homing as illustrated by computer tomography and magnetic resonance imaging, MnWOX -PEG enables effective destruction of mouse tumors under US stimulation. After accomplishing its therapeutic functions, MnWOX -PEG can be metabolized by the mouse body without any long-term toxicity. Herein, a new type of sono-sensitizing agent with high SDT efficacy, multimodal imaging functions, and rapid clearance is presented, an agent which is promising for noninvasive SDT cancer treatment.

Golden Exosomes Selectively Target Brain Pathologies in Neurodegenerative and Neurodevelopmental Disorders.

Exosomes, nanovesicles that are secreted by different cell types, enable intercellular communication at local or distant sites. Alhough they have been found to cross the blood brain barrier, their migration and homing abilities within the brain remain unstudied. We have recently developed a method for longitudinal and quantitative in vivo neuroimaging of exosomes based on the superior visualization abilities of classical X-ray computed tomography (CT), combined with gold nanoparticles as labeling agents. Here, we used this technique to track the migration and homing patterns of intranasally administrated exosomes derived from bone marrow mesenchymal stem cells (MSC-exo) in different brain pathologies, including stroke, autism, Parkinson's disease, and Alzheimer's disease. We found that MSC-exo specifically targeted and accumulated in pathologically relevant murine models brains regions up to 96 h post administration, while in healthy controls they showed a diffuse migration pattern and clearance by 24 h. The neuro-inflammatory signal in pathological brains was highly correlated with MSC-exo accumulation, suggesting that the homing mechanism is inflammatory-driven. In addition, MSC-exo were selectively uptaken by neuronal cells, but not glial cells, in the pathological regions. Taken together, these findings can significantly promote the application of exosomes for therapy and targeted drug delivery in various brain pathologies.

CT Imaging of Enzymatic Activity in Cancer Using Covalent Probes Reveal a Size-Dependent Pattern.

X-ray CT instruments are among the most available, efficient, and cost-effective imaging modalities in hospitals. The field of CT molecular imaging is emerging which relies mainly on the detection of gold nanoparticles and iodine-containing compounds directed to tagging a variety of abundant biomolecules. Here for the first time we attempted to detect enzymatic activity, while the low sensitivity of CT scanners to contrast reagents made this a challenging task. Therefore, we developed a new class of nanosized cathepsin-targeted activity-based probes (ABPs) for functional CT imaging of cancer. ABPs are small molecules designed to covalently modify enzyme targets in an activity-dependent manner. Using a CT instrument, these novel probes enable detection of the elevated cathepsin activity within cancerous tissue, thus creating a direct link between biological processes and imaging signals. We present the generation and biochemical evaluation of a library of ABPs tagged with different sized gold nanoparticles (GNPs), with various ratios of cathepsin-targeting moiety and a combination of different polyethylene glycol (PEG) protective layers. The most potent and stable GNP-ABPs were applied for noninvasive cancer imaging in mice. Surprisingly, detection of CT contrast from the tumor had reverse correlation to GNP size and the amount of targeting moiety. Interestingly, TEM images of tumor sections show intercellular lysosomal subcellular localization of the GNP-ABPs. In conclusion, we demonstrate that the covalent linkage is key for detection using low sensitive imaging modalities and the utility of GNP-ABPs as a promising tool for enzymatic-based CT imaging.

Uptake mechanism of metabolic-targeted gold nanoparticles.

AIM: To elucidate the interactions, uptake mechanisms and cytotoxicity profile of glucose-functionalized gold nanoparticles (2GF-GNPs), for expanding and advancing the recently proposed technology of metabolic-based cancer detection to a variety of cancer diseases. METHODS: Several cell types with different metabolic features were used to assess the involvement of GLUT-1 and different endocytosis pathways in 2GF-GNP uptake, and the cytotoxicity profile of 2GF-GNPs. RESULTS: Cellular uptake of 2GF-GNP strongly correlated with GLUT-1 surface expression, and occurred mainly through clathrin-mediated endocytosis. 2GF-GNPs showed no toxic effect on cell cycle and proliferation. CONCLUSION: These findings promote development of metabolic-based cancer detection technologies, and suggest that 2GF-GNPs may enable specific cancer detection in a wide range of tumors characterized by high GLUT-1 expression.

Nanoinformatics Revolutionizes Personalized Cancer Therapy.

Designing personalized cancer nanomedicines is a challenging process. The emerging field of nanoinformatics can facilitate this process by enabling computational design of nanocarrier-encapsulated drugs. Recent data show that quantitative structure-nanoparticle assembly calculations predict particle formation and size, and can lead to safer and more effective personalized cancer therapeutics.