Use Of Nanomedicine Research Articles

Safety Considerations of Cancer Nanomedicine—A Key Step toward Translation

The rate of translational effort of nanomedicine requires strategic planning of nanosafety research in order to enable clinical trials and safe use of nanomedicine in patients. Herein, the experiences that have emerged based on the safety data of classic liposomal formulations in the space of oncology are discussed, along with a description of the new challenges that need to be addressed according to the rapid expansion of nanomedicine platform beyond liposomes. It is valuable to consider the combined use of predictive toxicological assessment supported by deliberate investigation on aspects such as absorption, distribution, metabolism, and excretion (ADME) and toxicokinetic profiles, the risk that may be introduced during nanomanufacture, unique nanomaterials properties, and nonobvious nanosafety endpoints, for example. These efforts will allow the generation of investigational new drug-enabling safety data that can be incorporated into a rational infrastructure for regulatory decision-making. Since the safety assessment relates to nanomaterials, the investigation should cover the important physicochemical properties of the material that may lead to hazards when the nanomedicine product is utilized in humans.

Cancer Theranostics: Bridging Conventional and Nano-photodynamic Therapy

AbstractCancer is of various kinds, so are the treatment modalities. Worldwide, cancer is the second leading cause of death, accounting for a whopping 9.6 million deaths in 2018. Globally, approximately one in six deaths is attributed to cancer. Photodynamic therapy (PDT) is a therapeutic strategy for the treatment of superficial lesions, warts, Barrett’s esophagus, premalignant lesions, malignant tumors, and ophthalmic diseases. The literature on PDT is approximately one-third of that in radiation therapy, yet the clinical implementation of PDT in cancer is relatively less. Despite substantial research, the clinical application of photodynamic strategy in cancer therapy is still in its infancy with only a limited number of case studies reported so far. The limitations of the photosensitizer and the shallow depth of penetration of light source are the key technical impediments. However, the use of nanomedicine in PDT can overcome these obstacles. Thus, it is necessary to gain knowledge on how nanomaterials can be merged with PDT and how it can be utilized in cancer theranostics. In this article, the focus is to understand how PDT works and how it can be utilized in improving the sensitivity of the existing diagnostic and therapeutic techniques. The article also addresses the current challenges for PDT and the future prospects of this technique, particularly in the area of diagnosis and treatment of cancer.

The potential of micelleplexes as a therapeutic strategy for osteosarcoma disease.

Osteosarcoma (OS) is a rare aggressive bone, presenting low patient survival rate, high metastasis and relapse occurrence, mostly due to multi-drug resistant cells. To surpass that, the use of nanomedicine for the targeted delivery of genetic material, drugs or both have been extensively researched. In this review, we address the current situation of the disorder and some gene therapy options in the nanomedicine field that have been investigated. Among them, polymeric micelles (PM) are an advantageous therapeutic alternative highly explored for OS, as they allow for the targeted transportation of poorly water-soluble drugs to cancer cells. In addition, micelleplexes are PMs with cationic properties with promising features, such as the possibility for a dual therapy, which have made them an attractive research subject. The aim of this review article is to elucidate the application of a micelleplex formulation encapsulating the underexpressed miRNA145 to achieve an active targeting to OS cells and overcome multi-drug resistance, as a new and viable therapeutic strategy.

Hyaluronic Acid-Decorated Glycol Chitosan Nanoparticles for pH-Sensitive Controlled Release of Doxorubicin and Celecoxib in Nonsmall Cell Lung Cancer

Nonsmall cell lung cancer (NSCLC) is a leading cause of global cancer mortality. Recently, combinatorial treatment approaches have shown promise as they better address tumor heterogeneity. However, drug pharmacokinetics and tissue distribution differences remain problematic. To overcome these issues and improve therapeutic efficacies, the use of nanomedicines has been suggested. We devised a CD44 receptor target hyaluronic acid (HA)-decorated glycol chitosan (GC) nanoparticle which is conjugated to doxorubicin (DOX) by a pH-sensitive linker and coloaded celecoxib (CXB; HA-GC-DOX/CXB). Successful chemical conjugation of GC to DOX was confirmed and HA-GC-DOX/CXB showed ∼150 nm of uniform spherical shape. HA-GC-DOX/CXB were stable at pH 7.4 but steadily increased in size and released drugs at pH 6.0 and 4.0. In vitro NSCLC cells showed that DOX and CXB combination therapy has synergism in both free drug and nanoparticle formulation. In vivo NSCLC xenograft mice showed DOX and CXB exhibited a synergistic tumor suppressive effect in HA-GC-DOX/CXB. Furthermore, HA-GC-DOX/CXB dramatically inhibited tumor growth compared to other treatments as well as suppressed inflammation and metastasis-related gene/protein in the tumor tissues. Our findings demonstrate HA-GC-DOX/CXB is a potential anticancer therapy that controlled release under acidic tumor microenvironments and enhanced CD44 overexpressed tumor target efficacy.

Gold nanoclusters for biomedical applications: toward in vivo studies.

In parallel with the rapidly growing and widespread use of nanomedicine in the clinic, we are also witnessing the development of so-called theranostic agents that combine diagnostic and therapeutic properties. Among them, ultra-small gold nanoclusters (Au NCs) show promising potential due to their optical properties and activatable therapeutic activities under irradiation. Furthermore, due to their hydrodynamic diameter of smaller than 6 nm and unique biophysical properties, they also present intriguing behaviors in biological and physio-pathological environments. In this review, we aim to present the latest research studies published on such nanoparticles in animals. We also propose guidelines to identify the main physico-chemical parameters that govern the behaviour of Au NCs after administration in small animals, notably concerning their renal elimination and their ability to accumulate in tumors. Then, we present recent advances in their use as theranostic agents putting them in parallel with other contrast agents.

Nanocarrier drug resistant tumor interactions: novel approaches to fight drug resistance in cancer.

Cancer is one of the biggest healthcare concerns in our century, a disease whose treatment has become even more difficult following reports of drug-resistant tumors. When this happens, chemotherapy treatments fail or decrease in efficiency, leading to catastrophic consequences to the patient. This discovery, along with the fact that drug resistance limits the efficacy of current treatments, has led to a new wave of discovery for new methods of treatment. The use of nanomedicine has been widely studied in current years as a way to effectively fight drug resistance in cancer. Research in the area of cancer nanotechnology over the past decades has led to tremendous advancement in the synthesis of tailored nanoparticles with targeting ligands that can successfully attach to chemotherapy-resistant cancer by preferentially accumulating within the tumor region through means of active and passive targeting. Consequently, these approaches can reduce the off-target accumulation of their payload and lead to reduced cytotoxicity and better targeting. This review explores some categories of nanocarriers that have been used in the treatment of drug-resistant cancers, including polymeric, viral, lipid-based, metal-based, carbon-based, and magnetic nanocarriers, opening the door for an exciting field of discovery that holds tremendous promise in the treatment of these tumors.

Development of Promitil®, a lipidic prodrug of mitomycin c in PEGylated liposomes: From bench to bedside.

Several liposome products have been approved for the treatment of cancer. In all of them, the active agents are encapsulated in the liposome water phase passively or by transmembrane ion gradients. An alternative approach in liposomal drug delivery consists of chemically modifying drugs to form lipophilic prodrugs with strong association to the liposomal bilayer. Based on this approach, we synthesized a mitomycin c-derived lipidic prodrug (MLP) which is entrapped in the bilayer of PEGylated liposomes (PL-MLP, Promitil®), and activated by thiolytic cleavage. PL-MLP is stable in plasma with thiolytic activation of MLP occurring exclusively in tissues and is more effective and less toxic than conventional chemotherapy in various tumor models. PL-MLP has completed phase I clinical development where it has shown a favorable safety profile and a 3-fold reduction in toxicity as compared to free mitomycin c. Clinical and pharmacokinetic studies in patients with advanced colo-rectal carcinoma have indicated a significant rate of disease stabilization (39%) in this chemo-refractory population and significant prolongation of median survival in patients attaining stable disease (13.9months) versus progressive disease patients (6.35months). The pharmacokinetics of MLP was typically stealth with long T½ (~1day), slow clearance and small volume of distribution. Interestingly, a longer T½, and slower clearance were both correlated with disease stabilization and longer survival. This association of pharmacokinetic parameters with patient outcome suggests that arrest of tumor growth is related to the enhanced tumor localization of long-circulating liposomes and highlights the importance of personalized pharmacokinetic evaluation in the clinical use of nanomedicines. Another important area where PL-MLP may have an added value is in chemoradiotherapy, where it has shown a strong radiosensitizing effect in animal models based on a unique mechanism of enhanced prodrug activation and encouraging results in early human testing.

The Use of Nanomedicine for Targeted Therapy against Bacterial Infections.

The emergence of drug resistance combined with limited success in the discovery of newer and effective antimicrobial chemotherapeutics poses a significant challenge to human and animal health. Nanoparticles may be an approach for effective drug development and delivery against infections caused by multi-drug resistant bacteria. Here we discuss nanoparticles therapeutics and nano-drug delivery against bacterial infections. The therapeutic efficacy of numerous kinds of nanoparticles including nanoantibiotics conjugates, small molecules capped nanoparticles, polymers stabilized nanoparticles, and biomolecules functionalized nanoparticles has been discussed. Moreover, nanoparticles-based drug delivery systems against bacterial infections have been described. Furthermore, the fundamental limitation of biocompatibility and biosafety of nanoparticles is also conferred. Finally, we propose potential future strategies of nanomaterials as antibacterials.

Development of Kaempferol-Loaded Gelatin Nanoparticles for the Treatment of Corneal Neovascularization in Mice.

Cornea is the transparent layer in front of the eye that does not contain blood vessels. Among eye diseases, corneal neovascularization (NV) is one of the major causes of vision loss, since it can also lead to blindness. An herbal extraction containing flavonoid, kaempferol (KA), with antiangiogenic effect was chosen as a candidate drug for inhibited vessel formation. The use of nanomedicine has led to higher drug bioavailability and slow release of the drug as an effective therapeutic formulation in ocular drug delivery. In this study, we prepared gelatin nanoparticles (GNP) with kaempferol encapsulation (GNP-KA) for corneal NV treatment by topical delivery, i.e., eye drops. We found that GNP with/without KA loading was in the size of 85−150 nm, and its zeta potential was around 22−26 mV. The KA entrapment rate of GNP-KA was around 90−98%, and the loading rate was about 4.6%. The TEM results clearly indicated the GNP-KA NPs to be round spheres. The in vitro test involved the adoption of human umbilical vein endothelial cells (HUVECs) for coculture with these nanoparticles. From WST-8 assay, and cell migration examinations, it was evident that GNP-KA had the capacity to inhibit the cell viability and function of HUVECs. The results from in vivo tests such as ocular vessels observation, hematoxylin & eosin (H&E) stain, and metalloproteinases (MMP)/vascular endothelial growth factor (VEGF) quantification revealed the mice’s eyes with corneal NV treated by eye drops containing GNP-KA once daily for 7 days had better therapeutic effects with less vessels in-growths in the cornea, compared to the KA solution group by reducing the production of MMP and VEGF in the cornea. Therefore, we expected to achieve a comfortable treatment with a simple method using nanomedicine (GNP-KA) as ophthalmological agent delivered as eye drops.

Specific targeting cancer cells with nanoparticles and drug delivery in cancer therapy.

Nanotechnology has been the latest approach for diagnosis and treatment for cancer, which opens up a new alternative therapeutic drug delivery option to treat disease. Nanoparticles (NPs) display a broad role in cancer diagnosis and has various advantages over the other conventional chemotherapeutic drug delivery. NPs possess more specific and efficient drug delivery to the targeted tissue, cell, or organs and minimize the risk of side effects. NPs undergo passive and active mode of drug targets to tumor area with less elimination of the drug from the system. Size and surface characteristics of nanoparticles play a crucial role in modulating nanocarrier efficiency and the biodistribution of chemo drugs in the body. Several types of nanocarriers, such as polymers, dendrimers, liposome-based, and carbon-based, are studied widely in cancer therapy. Although FDA approved very few nanotechnology drugs for cancer therapy, a large number of studies are undergoing for the development of novel nanocarriers for potent cancer therapy. In this review, we discuss the details of the nano-based therapeutics and diagnostics strategies, and the potential use of nanomedicines in cancer therapy and cancer drug delivery.

PDG96 SURVEY ABOUT KNOWLEDGE OF NANOMEDICINES AMONG PHARMACISTS IN UKRAINE

To assess knowledge of nanomedicines among pharmacists in Ukraine and to outline the directions of further research. Survey was conducted in April, 2019 in the form of questionnaire that was sent to pharmacists in West region, Ukraine. Questionnaire consisted of introduction part (n=6) and specific questions on nanomedicines (n=14). Due to the preliminary character of the research, a total of 40 pharmacists took part in this study. The majority of voluntary respondents had higher pharmaceutical education (80%) and professional experience of more than 10 years (60%), most of them worked in pharmacies of LLC ownership (92.5%). Respondents assessed their knowledge of nanomedicines in 4 points from 10. 65% of pharmacists did not know about the safety of nanomedicines, the rest were sure about safety of those preparatios. 60% did not know about the effectiveness of nanomedicines and the same number of survey participants thought that nanomedicine drugs had another mechanism of action than traditional drugs. 97.5% of respondents would like to get more information about nanomedicines. 72.5% of survey participants thought that there is a need to implement normative documents for regulating nanomedicines in Ukraine and to add the information on active ingredients in nanosizes into the instruction for medical use of nanomedicines. The answers on questionnaire showed that knowledge level of nanomedicines among the Ukrainian pharmacists even with long professional experience is quite limited and pharmacists themselves understood this. This may be caused by the lack of normative regulation of nanomedicines in Ukraine. Therefore, educational programs for pharmacists are needed to raise awareness about the mechanisms of action, effectiveness and safety of nanopreparations. Normative regulation of nanomedicines in Ukraine also should be developed.

Critical considerations for targeting colorectal liver metastases with nanotechnology.

Colorectal cancer remains a significant cause of morbidity and mortality worldwide. Half of all patients develop liver metastases, presenting unique challenges for their treatment. The shortcomings of conventional chemotherapy has encouraged the use of nanomedicines; the application of nanotechnology in the diagnosis and treatment of disease. In spite of technological improvements in nanotechnology, the complexity of biological systems hinders the prospect of nanomedicines being applied in cancer therapy at the present time. This review highlights current biological barriers and discusses aspects of tumor biology together with the physicochemical features of the nanocarrier, that need to be considered in order to develop effective nanotherapeutics for colorectal cancer patients with liver metastases. It becomes clear that incorporating an interdisciplinary approach when developing nanomedicines should assure appropriate disease‐driven design and that this will form a critical step in improving their clinical translation.This article is characterized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

Nanoinformatics in Drug Delivery

AbstractThe use of nanomedicine for targeted drug delivery, though well established, is still a growing and developing field of research with potential benefits to many biomedical problems. There is a plethora of nano‐carriers with myriads of designs of shapes, sizes and composition that involves complex, trial and error based preparation protocols. The digital age brought an information revolution with automated data analysis, machine learning and data mining applied to almost every field of research including drug delivery. Indeed, nanomedicine has benefitted from the use of data science and information science to optimize, standardize, and understand the synthesis, characterization, and biological effects of nanomaterials. This short review will describe several concepts and a few examples of nanoinformatics, including Nano‐Quantitative Structure‐Activity Relationship (Nano‐QSAR), the use of computational methods for predicting different properties of nanomedicine in drug delivery and propose an outlook for the future.

Nanomedicines for the Delivery of Biologics.

A special symposium of the Academy of Pharmaceutical Sciences Nanomedicines Focus Group reviewed the current status of the use of nanomedicines for the delivery of biologics drugs. This meeting was particularly timely with the recent approval of the first siRNA-containing product Onpattro™ (patisiran), which is formulated as a lipid nanoparticle for intravenous infusion, and the increasing interest in the use of nanomedicines for the oral delivery of biologics. The challenges in delivering such molecules were discussed with specific emphasis on the delivery both across and into cells. The latest developments in Molecular Envelope Technology® (Nanomerics Ltd, London, UK), liposomal drug delivery (both from an academic and industrial perspective), opportunities offered by the endocytic pathway, delivery using genetically engineered viral vectors (PsiOxus Technologies Ltd, Abingdon, UK), Transint™ technology (Applied Molecular Transport Inc., South San Francisco, CA, USA), which has the potential to deliver a wide range of macromolecules, and AstraZeneca’s initiatives in mRNA delivery were covered with a focus on their uses in difficult to treat diseases, including cancers. Preclinical data were presented for each of the technologies and where sufficiently advanced, plans for clinical studies as well as early clinical data. The meeting covered the work in progress in this exciting area and highlighted some key technologies to look out for in the future.

Silver-Nanoparticle-Mediated Therapies in the Treatment of Pancreatic Cancer

Pancreatic cancer is an extremely aggressive disease for which patient prognosis is poor and survival is extremely unlikely. It is an extremely under-represented cancer in the research field because of the dense tumors formed and complexities surrounding treatment requirements. The use of nanomedicines in cancer therapy has been explored over the past few decades. Such nanomedicines are slowly coming to fruition in the clinical setting. One such platform that may possess promise in the fight against pancreatic cancer is the use of colloidal silver. Silver nanoparticles have shown potential in other cancer types over a host of treatment strategies, and these are likely to be translatable into pancreatic cancer. This review will focus on the potential use of silver nanoparticles in pancreatic cancer therapy, reporting on a range of different strategies being employed that may be directly applicable in the improvement of clinical outcomes for pancreatic cancer patients.

Therapeutic Opportunities in Neuroblastoma Using Nanotechnology.

Neuroblastoma (NB) is the most common extracranial solid tumor preferentially occurring in preschoolers. Its characteristic aggressiveness and heterogeneous clinical behavior are especially visible in relapsed or refractory cases and hamper therapeutic success. Although the introduction of novel antitumor agents, such as dinutuximab, isotretinoin, irinotecan, or I-131- metaiodobenzylguanidine, has increased survival rates, the situation in high-risk NB remains dismal. Moreover, treatment is particularly aggressive in these patients, leading to short- and long-term toxicities. The extensive research performed using nanotechnology in recent decades has prompted its application as a therapeutic alternative to overcome some of the common limitations of conventional chemotherapy. Nevertheless, the therapeutic role of nanomedicine in pediatric tumors like NB is not fully elucidated, and to date, only albumin-bound paclitaxel nanoparticles have reached clinic stages. In this review, we summarize the current therapeutic strategies for NB with special attention to the use of nanomedicine. We also highlight the preclinical studies on passive and active targeting nanodelivery of therapeutics in experimental NB models.

Nanoparticle modification in biological media: implications for oral nanomedicines.

Nanomedicine has shown potential in enabling oral administration of poorly absorbable drugs, such as biologics. As part of the process related to optimisation of the safety and efficacy of nanomedicines, it is imperative that the interaction of nanoparticles with the biological systems – including the gut – is fully characterised. In this article, we provide an overview of the major mechanisms by which nanoparticles may transform upon introduction in biological media. Specifically, the phenomena of association, dissolution and biomolecule adsorption are discussed, together with factors which influence the occurrence of each phenomenon. The implications of these phenomena within the context of therapeutic action of nanomedicines, which includes reduced targeting efficiency, are also explored. Finally, we will comment on nanoparticle modification within the gut environment, including the currently available gastrointestinal models for the study of nano-bio interactions, with implications in the area of nanomedicines for oral administration.

Alliance with EPR Effect: Combined Strategies to Improve the EPR Effect in the Tumor Microenvironment.

The use of nanomedicine for cancer treatment takes advantage of its preferential accumulation in tumors owing to the enhanced permeability and retention (EPR) effect. The development of cancer nanomedicine has promised highly effective treatment options unprecedented by standard therapeutics. However, the therapeutic efficacy of passively targeted nanomedicine is not always satisfactory because it is largely influenced by the heterogeneity of the intensity of the EPR effect exhibited within a tumor, at different stages of a tumor, and among individual tumors. In addition, limited data on EPR effectiveness in human hinders further clinical translation of nanomedicine. This unsatisfactory therapeutic outcome in mice and humans necessitates novel approaches to improve the EPR effect. This review focuses on current attempts at overcoming the limitations of traditional EPR-dependent nanomedicine by incorporating supplementary strategies, such as additional molecular targeting, physical alteration, or physiological remodeling of the tumor microenvironment. This review will provide valuable insight to researchers who seek to overcome the limitations of relying on the EPR effect alone in cancer nanomedicine and go “beyond the EPR effect”.

Potential Use of Nanomedicine for the Anti-inflammatory Treatment of Neurodegenerative Diseases.

Neurodegenerative diseases, like Alzheimer´s and Parkinson´s disease, are a group of disorders that have in common their increasingly high prevalence along with the shortage of effective treatments. In addition, the scientific community faces the challenge of getting the drugs used in these treatments to cross the blood-brain barrier (BBB) and reach the brain in sufficient concentration to be able to exert its effect. Hence, researchers across multiple disciplines are working together in order to improve the ability of therapeutics to penetrate the BBB. In this sense, the use of nanomedicine, nanoscale structures for drug delivery, exhibits a really high therapeutic potential in the field of neurodegenerative diseases therapy. Since there is new evidence that neuroinflammation produced by reactive microglia contributes to the activation and pathogenesis of neurological disorders, many investigations focus on the identification of new targets whose inhibition can reduce, totally or partially, microglial activation. This review analyzes a wide variety of compounds as possible candidates to achieve this target, from compounds with a natural origin to anti-diabetics, antidepressants, antibiotics and hormones. We also discuss the different strategies to enhance the capacity of these compounds to cross the BBB. Although this review focuses on PLGA nanoparticles as one of the most versatile drug delivery nanosystems, we also describe other strategies, such as direct intranasal administration (nose-tobrain), novel viral vectors and novel implanted catheters.

Abstract 3727: Dual acidic pH targeted mesoporous silica nanoparticles for noninvasive detection of triple negative breast cancer

Abstract Purpose: Current screening methods for triple negative breast cancer suggest the presence and size of tumor, but do not identify the tumor microenvironment. The inability to determine precise tumor location and position following diagnosis impedes medical confidence in surgical resection and radiation therapy. Theranostic nanoparticles can be targeted for dye and drug delivery to facilitate non-invasive characterization and treatment of malignancies. Combinational use of nanomedicine and Multispectral Optoacoustic Tomography (MSOT) renders high resolution images through ultrasonic detection of thermoelastic dye expansion (the optoacoustic effect). Approaches in nanomedicine are steadily growing, but clinical evaluation relies on minimizing off-target accumulation and controlling cargo release. We evaluated a mesoporous silica nanoparticles with pH-sensitive chitosan gatekeeper and tumor targeting V3 pH low-insertion peptide (V3 pHLIP) conjugation (V3-CMSN-780) for dual acidic pH targeted delivery to triple negative breast cancer. Methods: Mesoporous silica nanoparticles were synthesized around a structural skeleton of hexadecyltrimethylammonium bromide (CTAB). CTAB was removed from the particles through repeated dialysis. Subsequent particles were characterized with digital light scattering (DLS) and zetasizer to confirm particle size and zeta potential. Mesoporous nanoparticles were then coated with chitosan for extracellular acidic pH selectivity and functionalized with variant 3 pH low-insertion peptide (V3 pHLIP) to promote anchoring of the particle to tumor cells. Functionalized nanoparticles (V3-CMSN) were loaded with NIR 780 (5 mg/mL) and delivered to MDA-MB-231 and MDA-MB-468 malignant cell lines at pH 7.4, 6.8, and 6.6 to confirm pH-sensitive dye release into the cells with Near Infrared fluorescent imaging. V3-CMSN treated cells were inserted into tissue mimicking phantoms which were evaluated using MSOT. Results: The size of V3-CMSN-780 was 35 d. nm with a zeta potential of 25 mV. V3-CMSN were loaded with 780 dye with a dye loading efficiency of 77%. Cellular uptake of V3-CMSN-780 within MDA-MB-231 cells was 2152 a.u., 5242 a.u., and 3639 a.u. at pHs 7.4, 6.8, and 6.6, respectively, based NIR fluorescent imaging. Treatment of MDA-MB-231 cells with V3-CMSN-780 within tissue mimicking phantoms also confirmed acidic pH selectivity of the particles with a 6X and 4X accumulation of particles at pH 6.8 and 6.6 as compared to pH 7.4. While similar results were observed in MDA-MB-468 cells with NIR fluorescent imaging, MSOT imaging indicated that MDA-MB-468 cells treated at pH 6.8 and 6.6 had increased 780 signal, 110X and 16X, incomparison to pH 7.4. Conclusion: Successful dual targeting of breast tumor cells provides a foundation for later in vivo and ex vivo studies using V3-780-CMSNs to deliver diagnostic and therapeutic cargo to malignant breast tissue. Citation Format: Joshua T. Hayes, Abhilash Samykutty, Molly McNally, Alexandra Thomas, Akiko Chiba, William Grizzle, Karen M. Winkfield, Lacey R. McNally. Dual acidic pH targeted mesoporous silica nanoparticles for noninvasive detection of triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3727.