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Tumor recurrence following surgery is a common and unresolved medical problem of great importance since surgery is the most widely used treatment for solid-mass tumors worldwide. A contributing factor to tumor recurrence is the presence of residual tumor remaining at or near the surgical site following surgery. Goal: The primary objective of this study was to develop and evaluate an image-guided surgery system based on a near-infrared, handheld excitation source and spectrograph in combination with a widefield video imaging system. Methods: This system was designed to detect the fluorescence of near-infrared contrast agents and, in particular, indocyanine green (ICG). The imaging system was evaluated for its optical performance and ability to detect the presence of ICG in tumors in an ectopic murine tumor model as well as in spontaneous tumors arising in canines. Results: In both settings, an intravenous ICG infusion provided tumor contrast. In both the murine models and surgical specimens from canines, ICG preferentially accumulated in tumor tissue compared to surrounding normal tissue. The resulting contrast was sufficient to distinguish neoplasia from normal tissue; in the canine surgical specimens, the contrast was sufficient to permit identification of neoplasia on the marginal surface of the specimen. Conclusion: These results demonstrate a unique concept in image-guided surgery by combining local excitation and spectroscopy with widefield imaging. Significance: The ability to readily detect ICG in canines with spontaneous tumors in a clinical setting exemplifies the potential for further clinical translation; the promising results of detecting neoplasia on the marginal specimen surface underscore the clinical utility. [ABSTRACT FROM PUBLISHER]

Surgery is one of the most effective and widely used procedures in treating human cancers, but a major problem is that the surgeon often fails to remove the entire tumor, leaving behind tumor-positive margins, metastatic lymph nodes, and/or satellite tumor nodules. Here we report the use of a hand-held spectroscopic pen device (termed SpeciroPen) and near-infrared contrast agents for intraoperative detection of malignant tumors, based on wavelength-resolved measurements of fluorescence and surface-enhanced Raman scattering (SERS) signals. The SpectroPen utilizes a near-infrared diode laser (emitting at 785 urn) coupled to a compact head unit for light excitation and collection. This pen-shaped device effectively removes silica Raman peaks from the fiber optics and attenuates the reflected excitation light, allowing sensitive analysis of both fluorescence and Raman signals. Its overall performance has been evaluated by using a fluorescent contrast agent (indocyanine green, or ICG) as well as a surface-enhanced Raman scattering (SERS) contrast agent (pegylated colloidal gold). Under in vitro conditions, the detection limits are approximately 2-5 x 10-11 M for the indocyanine dye and 0.5-1 x 10-13 M for the SERS contrast agent. Ex vivo tissue penetration data show attenuated but resolvable fluorescence and Rainan signals when the contrast agents are buried 5-10mm deep in fresh animal tissues. In vivo studies using mice bearing bioluminescent 4T1 breast tumors further demonstrate that the tumor borders can be precisely detected preoperatively and intraoperatively, and that the contrast signals are strongly con-elated with tumor bioluminescence. After surgery, the SpeciroPen device permits further evaluation of both positive and negative tumor margins around the surgical cavity, raising new possibilities for real-lime tumor detection and image-guided surgery. [ABSTRACT FROM AUTHOR]

Strain can have a large influence on the properties of materials at the nanoscale. The effect of lattice strain on semiconductor devices has been widely studied, but its influence on colloidal semiconductor nanocrystals is still poorly understood. Here we show that the epitaxial deposition of a compressive shell (ZnS, ZnSe, ZnTe, CdS or CdSe) onto a soft nanocrystalline core (CdTe) to form a lattice-mismatched quantum dot can dramatically change the conduction and valence band energies of both the core and the shell. In particular, standard type-I quantum-dot behaviour is replaced by type-II behaviour, which is characterized by spatial separation of electrons and holes, extended excited-state lifetimes and giant spectral shifts. Moreover, the strain induced by the lattice mismatch can be used to tune the light emission—which displays narrow linewidths and high quantum yields—across the visible and near-infrared part of the spectrum (500–1,050 nm). Lattice-mismatched core–shell quantum dots are expected to have applications in solar energy conversion, multicolour biomedical imaging and super-resolution optical microscopy. [ABSTRACT FROM AUTHOR]

Simple Summary: Neoadjuvant chemotherapy has risen in clinical use for the treatment of pancreatic cancer over the past few decades. Many patients now undergo prior treatment before surgical resection to aid in downstaging the tumor for a potentially improved surgical outcome. Potential targeted therapies such as fluorescence-guided surgery often rely on the upregulated protein expression in the tumor. Therefore, it is important to understand the impact of neoadjuvant therapy on tumor protein expression, as protein expression may be altered by chemotherapy treatment. The aim of our study was to evaluate the expression of Mucin 16 (MUC16) after neoadjuvant chemotherapy in pancreatic ductal adenocarcinoma tissue. This study found that MUC16 expression was retained in the tumor following neoadjuvant chemotherapy treatment regimens. These findings may have a broad impact on the delivery of MUC16-targeted therapies before and after neoadjuvant chemotherapy treatment. Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Currently, surgical resection is the only potentially curative treatment. Unfortunately, less than 20% of PDAC patients are eligible for surgical resection at diagnosis. In the past few decades, neoadjuvant chemotherapy treatment (NCT) has been investigated as a way to downstage PDAC tumors for surgical resection. Fluorescence-guided surgery (FGS) is a technique that can aid in increasing complete resection rates by enhancing the tumor through passive or active targeting of a contrast agent. In active targeting, a probe (e.g., antibody) binds a protein differentially upregulated in the tumor compared to normal tissue. Mucin 16 (MUC16), a transmembrane glycoprotein, has recently been explored as an FGS target in preclinical tumor models. However, the impact of chemotherapy on MUC16 expression is unknown. Methods: To investigate this issue, immunohistochemistry was performed on PDAC patient samples. Results: We found that MUC16 expression was retained after NCT in patient samples (mean expression = 5.7) with minimal change in expression between the matched diagnostic (mean expression = 3.66) and PDAC NCT patient samples (mean expression = 4.5). Conclusions: This study suggests that MUC16 is a promising target for FGS and other targeted therapies in PDAC patients treated with NCT. [ABSTRACT FROM AUTHOR]

Background/Objectives: Pancreatic cancer is the third leading cause of death related to cancer. The only possible cure presently is complete surgical resection; however, this is limited by difficulty in clearly defining tumor margins. Enhancement of the visualization of pancreatic ductal adenocarcinoma (PDAC) tumor margins using near-infrared dye-conjugated tumor-specific antibodies was pioneered by using anti-CEA, anti-CA19.9, and anti-MUC5AC in orthotopic mouse models of pancreatic cancer. Recently, an antibody to Mucin 4 (MUC4) conjugated to a fluorescent probe has shown promise in targeting colon tumors in orthotopic mouse models. Methods: In the present study, we targeted pancreatic cancer using an anti-MUC4 antibody conjugated to IRDye800 (anti-MUC4-IR800) in orthotopic mouse models. Two pancreatic cancer human cell lines were used, SW1990 and CD18/HPAF. Results: Anti-MUC4-IR800 targeted the two pancreatic cancer cell line tumors in orthotopic mouse models with high tumor-to-pancreas ratios and high tumor-to-liver ratios, with greater targeting seen in SW1990. Conclusions: The present results suggest anti-MUC4-IR800's potential to be used in fluorescence-guided surgical resection of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Surgical resection continues to function as the primary treatment option for most solid tumors. However, the detection of cancerous tissue remains predominantly subjective and reliant on the expertise of the surgeon. Surgery that is guided by fluorescence imaging has shown clinical relevance as a new approach to detecting the primary tumor, tumor margins, and metastatic lymph nodes. It is a technique to reduce recurrence and increase the possibility of a curative resection. While significant progress has been made in developing this emerging technology as a tool to assist the surgeon, further improvements are still necessary. Refining imaging agents and tumor targeting strategies to be a precise and reliable surgical strategy is essential in order to translate this technology into patient care settings. This review seeks to provide a comprehensive update on the most recent progress of fluorescence-guided surgery and its translation into the clinic. By highlighting the current status and recent developments of fluorescence image-guided surgery in the field of surgical oncology, we aim to offer insight into the challenges and opportunities that require further investigation. [ABSTRACT FROM AUTHOR]

Accurately identifying metastatic disease is critical to directing the appropriate treatment in pancreatic cancer. Mucin 5AC is overexpressed in pancreatic cancer but absent in normal pancreas tissue. The present proof-of-concept study demonstrates the efficacy of an anti-mucin 5AC antibody conjugated to an IR800 dye (MUC5AC-IR800) to preferentially label a liver metastasis of pancreatic cancer (Panc Met) in a unique patient-derived orthotopic xenograft (PDOX) model. In orthotopic models, the mean tumor to background ratio was 1.787 (SD ± 0.336), and immunohistochemistry confirmed the expression of MUC5AC within tumor cells. MUC5AC-IR800 provides distinct visualization of pancreatic cancer liver metastasis in a PDOX mouse model, demonstrating its potential utility in staging laparoscopy and fluorescence-guided surgery. [ABSTRACT FROM AUTHOR]

A selective, sensitive, and rapid liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantitation of ICG in rat plasma. The chromatographic separation was achieved using an ACE excel C18 (3 µm, 50 × 3.0 mm) column, with a mobile phase composition of 0.1% formic acid and 0.1% formic acid in acetonitrile, using a gradient flow at a rate of 0.3 mL/min. The MS was operated at a unit resolution in the multiple reaction monitoring mode, using the precursor ion → product ion combinations of 753.3 → 330.2 m/z (ICG) and 747.45 → 717.50 (Cy7.5 amine) with a run time of 5 min. The assay was linear over a concentration range of 1–1000 ng/mL with a regression coefficient (r2) of 0.998 or better. The inter and intra-batch precision (% relative standard deviation, %RSD) was lower than 13.5%, with accuracy (%Bias) between −10.03% and 11.56%. The ICG was stable under laboratory storage and handling conditions. The validated method was successfully applied to preclinical pharmacokinetic (PK) studies of ICG at a dose of 0.39 mg/kg in rats. PK parameters suggested the highest plasma concentration within 2 min of intravenous dosing with restricted systemic distribution and rapid clearance. [ABSTRACT FROM AUTHOR]

[Display omitted] • Sensing tool for identifying antimicrobial-resistant Staphylococcus aureus strains. • Fluorescent sensor array pre-adsorbed on paper microzone plates for better efficiency. • Classification of laboratory and clinical S. aureus strains powered by machine learning. • Sensor identifies biofilms associated with antimicrobial-resistant S. aureus strains. • Rapid, low-volume identification with >90% classification accuracy. Staphylococcus aureus , a versatile human pathogen, significantly impacts global health causing a broad spectrum of medical conditions that range from minor skin infections to life-threatening diseases. The clinical importance of S. aureus is underscored by its resistance to multiple antibiotics and formation of biofilms, providing protection against antimicrobials and immune responses. To date, the identification of antimicrobial-resistant (AMR) S. aureus strains, such as methicillin-resistant S. aureus (MRSA) and vancomycin-intermediate S. aureus (VISA), requires time-consuming and expensive methodologies, including culture-based, molecular, and phenotypic techniques. Previously, we developed a paper-based ratiometric sensor array composed of fluorescent sensor dyes (3-hydroxyflavone derivatives) pre-adsorbed on paper microzone plates. Combined with machine learning algorithms such as neural networks, this sensor effectively discriminated 16 bacterial species and determined their Gram status. In this study, we evaluate its ability to distinguish antibiotic-resistant S. aureus strains and their biofilms. Our results demonstrate that the sensor array, in conjunction with LDA and neural networks, successfully differentiated three common laboratory MRSA strains from three methicillin-susceptible S. aureus (MSSA) strains with 82.5% accuracy. Furthermore, using support vector machines, this sensor was able to distinguish and categorically classify MRSA, MSSA, and VISA clinical isolates with 97.5% accuracy. Remarkably, beyond distinguishing planktonic cultures, this sensor array demonstrated a formidable capability to discriminate AMR S. aureus biofilms, achieving over 80% accuracy. Combined, the results of this study highlight the paper-based sensor array's significant potential as a robust diagnostic tool to accurately, rapidly, and easily identify drug-resistant S. aureus strains in clinically relevant settings. [ABSTRACT FROM AUTHOR]

Abstract: Semiconductor quantum dots (QDs) are tiny light-emitting particles on the nanometer scale, and are emerging as a new class of fluorescent labels for biology and medicine. In comparison with organic dyes and fluorescent proteins, they have unique optical and electronic properties, with size-tunable light emission, superior signal brightness, resistance to photobleaching, and broad absorption spectra for simultaneous excitation of multiple fluorescence colors. QDs also provide a versatile nanoscale scaffold for designing multifunctional nanoparticles with both imaging and therapeutic functions. When linked with targeting ligands such as antibodies, peptides or small molecules, QDs can be used to target tumor biomarkers as well as tumor vasculatures with high affinity and specificity. Here we discuss the synthesis and development of state-of-the-art QD probes and their use for molecular and cellular imaging. We also examine key issues for in vivo imaging and therapy, such as nanoparticle biodistribution, pharmacokinetics, and toxicology. [Copyright &y& Elsevier]

Neuroblastoma is the most commonly diagnosed extracranial solid tumor in children. The patients with aggressive metastatic disease or refractory/relapsed neuroblastoma currently face a dismally low chance of survival. Thus, there is a great need for more effective therapies for this illness. In previous studies, we, as well as others, showed that the immune cell chemoattractant C-C motif chemokine ligand 21 (CCL21) is effective as an intratumoral therapy able to slow the growth of cancers. In this current study, we developed and tested an injectable, slow-release, uniform, and optimally loaded alginate nanoformulation of CCL21 as a means to provide prolonged intratumoral treatment. The alginate-nanoformulated CCL21, when injected intratumorally into mice bearing neuroblastoma lesions, significantly prolonged survival and decreased the tumor growth rate compared to CCL21 alone, empty nanoparticles, or buffer. Notably, we also observed complete tumor clearance and subsequent full protection against tumor rechallenge in 33% of nanoformulated CCL21-treated mice. Greater intratumoral presence of nanoformulated CCL21, compared to free CCL21, at days 1 and 2 after treatment ended was confirmed through fluorescent labeling and tracking. Nanoformulated CCL21-treated tumors exhibited a general pattern of prolonged increases in anti-tumor cytokines and relatively lower levels of pro-tumor cytokines in comparison to tumors treated with CCL21 alone or buffer only. Thus, this novel nanoformulation of CCL21 is an effective treatment for neuroblastoma, and may have potential for the delivery of CCL21 to other types of solid tumors in the future and as a slow-release delivery modality for other immunotherapies Unlabelled Image [ABSTRACT FROM AUTHOR]

Purpose: Negative surgical margins (NSMs) have favorable prognostic implications in breast tumor resection surgery. Fluorescence image-guided surgery (FIGS) has the ability to delineate surgical margins in real time, potentially improving the completeness of tumor resection. We have recently developed indocyanine green (ICG)-loaded self-assembled hyaluronic acid (HA) nanoparticles (NanoICG) for solid tumor imaging, which were shown to enhance intraoperative contrast.Procedures: This study sought to assess the efficacy of NanoICG on completeness of breast tumor resection and post-surgical survival. BALB/c mice bearing iRFP+/luciferase+ 4T1 syngeneic breast tumors were administered NanoICG or ICG, underwent FIGS, and were compared to bright light surgery (BLS) and sham controls.Results: NanoICG increased the number of complete resections and improved tumor-free survival. This was a product of improved intraoperative contrast enhancement and the identification of a greater number of small, occult lesions than ICG and BLS. Additionally, NanoICG identified chest wall invasion and predicted recurrence in a model of late-stage breast cancer.Conclusions: NanoICG is an efficacious intraoperative contrast agent and could potentially improve surgical outcomes in breast cancer. [ABSTRACT FROM AUTHOR]

The advent of nanomedicine has rejuvenated the need for increased understanding of the fundamental physicochemical properties of polymeric amphiphiles. Hyaluronic acid (HA) is a hydrophilic polysaccharide that is frequently conjugated to hydrophobic moieties and then used to entrap dyes and therapeutics. Here, we develop computational models to examine the effects of the hydrophobic modification on supramolecular behavior among three systematically designed HA derivatives substituted with alkyl chains of increasing length. Our simulations coalesce with experimentally obtained results to demonstrate the dependence of supramolecular behavior on intramolecular forces. We show that the formation of clearly defined hydrophobic domains in samples of octadecylamine-modified HA compared to HA conjugates with shorter alkyl chains is a result of more favorable hydrophobic interactions. Trends in hydrodynamic radius and polydispersity are observed in experimental results that coalesce with theoretical calculations, suggesting that supramolecular properties are dependent on the physicochemical characteristics of individual polymer strands. [ABSTRACT FROM AUTHOR]

Fluorescent nanomaterials require high colloidal stability for effective use in imaging and sensing applications. We herein report the synthesis of carbazole-based organic fluorescent nanoaggregates, and demonstrate the superior colloidal stability of alkyl-substituted dye aggregates over their non-alkylated analogs. The role of alkyl chains in self-assembly and stability of such nanoaggregates is discussed based on both experimental and molecular dynamics simulation data, and spectral characteristics of the precursor dyes and their aggregates are described. The obtained results provide new insights on development of colloidally stable organic fluorescent nanomaterials with low polydispersity. [ABSTRACT FROM AUTHOR]

The excited-state dynamics of an aniline-triazine electron donor-acceptor dyad with an alkyne spacer has been investigated using a combination of ultrafast broadband mid-IR and visible transient absorption and fluorescence spectroscopies. The transient IR data reveal the occurrence of an efficient alkyne to allene isomerization of the spacer with a time constant increasing from a few hundreds of femtoseconds to a few picoseconds with solvent viscosity. This process is faster than the vibrational cooling of the Franck-Condon excited state, indicative of nonequilibrium dynamics. The transient electronic absorption and fluorescence data evidence that this transformation is accompanied by a charge separation between the donor and the acceptor subunits. The allene character of the spacer implies an orthogonal orientation of the donor and acceptor moieties, similar to that proposed for twisted intramolecular charge-transfer states. Such states are often invoked in the excited-state dynamics of donor-acceptor dyads, but their involvement could never be unambiguously evidenced spectroscopically. The alkyne-allene isomerization involves not only a torsional motion but also a bending of the molecule due to the sp to sp2 rehybridization of one of the alkyne carbon atoms. This twisted and rehybridized intramolecular charge transfer ("TRICT") state decays back to the planar and linear alkyne ground state on a time scale decreasing from a few hundred to ten picoseconds upon going from weakly to highly polar solvents. The different solvent dependencies reveal that the dynamics of the allene buildup are controlled by the structural changes, whereas the decay is limited by the charge recombination step. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is difficult to resect due to its unique challenges, often leading to incomplete tumor resections. Fluorescence-guided surgery (FGS), also known as intraoperative molecular imaging and optical surgical navigation, is an intraoperative tool that can aid surgeons in complete tumor resection through an increased ability to detect the tumor. To target the tumor, FGS contrast agents rely on biomarkers aberrantly expressed in malignant tissue compared to normal tissue. These biomarkers allow clinicians to identify the tumor and its stage before surgical resection and provide a contrast agent target for intraoperative imaging. Mucins, a family of glycoproteins, are upregulated in malignant tissue compared to normal tissue. Therefore, these proteins may serve as biomarkers for surgical resection. Intraoperative imaging of mucin expression in pancreatic cancer can potentially increase the number of complete resections. While some mucins have been studied for FGS, the potential ability to function as a biomarker target extends to the entire mucin family. Therefore, mucins are attractive proteins to investigate more broadly as FGS biomarkers. This review summarizes the biomarker traits of mucins and their potential use in FGS for pancreatic cancer. [Display omitted] • Mucins can be differentially or uniquely expressed in pancreatic cancer allowing them to serve as contrast agent targets. • Fluorescently-labeled, mucin-targeting molecules, e.g. antibodies, can intraoperatively illuminate pancreatic cancer. • Intraoperative imaging, or fluorescence-guided surgery, can potentially increase the rate of complete tumor resection. • Mucin-targeting fluorophores are in preclinical development and could complement other surgical imaging agents. [ABSTRACT FROM AUTHOR]

Peripherally inserted central catheters (PICCs) are hollow polymeric tubes that transport nutrients, blood and medications to neonates. To determine proper PICC placement, frequent X-ray imaging of neonates is performed. Because X-rays pose severe health risks to neonates, safer alternatives are needed. We hypothesize that near infrared (NIR) polymer composites can be fabricated into catheters by incorporating a fluorescent dye (IRDye 800CW) and visualized using NIR imaging. To fabricate catheters, polymer and dye are dry mixed and pressed, sectioned, and extruded to produce hollow tubes. We analyzed surface roughness, stiffness, dye retention, NIR contrast intensity, and biocompatibility. The extrusion process did not significantly alter the mechanical properties of the polymer composites. Over a period of 23 days, only 6.35 ± 5.08% dye leached out of catheters. The addition of 0.025 wt% dye resulted in a 14-fold contrast enhancement producing clear PICC images at 1 cm under a tissue equivalent. The addition of IRDye 800CW did not alter the biocompatibility of the polymer and did not increase adhesion of cells to the surface. We successfully demonstrated that catheters can be imaged without the use of harmful radiation and still maintain the same properties as the unaltered medical grade equivalent. [ABSTRACT FROM AUTHOR]

The hybrid spectral micro-computed tomography (CT) architecture integrates a conventional imaging chain and an interior spectral imaging chain, and has been proven to be an important development in spectral CT. The motivation for this study is to minimize X-ray exposure for hybrid spectral micro-CT using both simulated and experimental scan data while maintaining the spectral fidelity of the reconstruction. Three elements of the hybrid scan protocol are investigated: truncation of the interior spectral chain and the numbers of projections for each of the global and interior imaging chains. The effect of these elements is quantified by analyzing how each affects the reconstructed spectral accuracy. The results demonstrate that there is significant scope for reduction of radiation exposure in the hybrid scan protocol. It appears decreasing the number of conventional projections offers the most potential for exposure reduction, while further reduction is possible by decreasing the interior FOV and number of spectral projections. SCANNING 36:444-455, 2014. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Spectral CT has proven an important development in biomedical imaging, and there have been several publications in the past years demonstrating its merits in pre-clinical and clinical applications. In 2012, Xu reported that near-term implementation of spectral micro-CT could be enhanced by a hybrid architecture: a narrow-beam spectral “interior” imaging chain integrated with a traditional wide-beam “global” imaging chain. This hybrid integration coupled with compressive sensing (CS)-based interior tomography demonstrated promising results for improved contrast resolution, and decreased system cost and radiation dose. The motivation for the current study is implementation and evaluation of the hybrid architecture with a first-of-its-kind hybrid spectral micro-CT system. Preliminary results confirm improvements in both contrast and spatial resolution. This technology is shown to merit further investigation and potential application in future spectral CT scanner design. [ABSTRACT FROM PUBLISHER]

Abstract: The purpose of this study is to investigate how the structures of polydisulfide Gd(III) complexes affect their pharmacokinetics and in vivo contrast enhancement as biodegradable macromolecular MRI contrast agents. A negatively charged polydisulfide Gd(III) complex, (Gd-DTPA)–cystine copolymers (GDCP), and a neutral agent, (Gd-DTPA)–cystine diethyl ester copolymers (GDCEP), with different molecular weights were prepared and characterized. The MRI contrast enhancement of the agents was studied in mice. Neutral GDCEP showed more rapid degradation than negatively charged GDCP in the blood plasma. Consequently, GDCP resulted in more significant and prolonged contrast enhancement in the blood pool and liver than GDCEP. The size of GDCEP did not significantly affect its in vivo contrast enhancement due to rapid degradation and clearance from the blood circulation. The increase in the molecular weight of GDCP resulted in prolonged in vivo contrast enhancement in the blood pool. The structural modification of polydisulfide Gd(III) complexes resulted in biodegradable macromolecular MRI contrast agents with different degradability and in vivo contrast enhancement. [Copyright &y& Elsevier]

Image 1 Antiretroviral therapy (ART) has improved the quality and duration of life for people living with human immunodeficiency virus (HIV) infection. However, limitations in drug efficacy, emergence of viral mutations and the paucity of cell-tissue targeting remain. We posit that to maximize ART potency and therapeutic outcomes newer drug formulations that reach HIV cellular reservoirs need be created. In a step towards achieving this goal we harnessed the aggregation-induced emission (AIE) property of the non-nucleoside reverse transcriptase inhibitor rilpivirine (RPV) and used it as a platform for drug cell and subcellular tracking. RPV nanocrystals were created with endogenous AIE properties enabling the visualization of intracellular particles in cell and tissue-based assays. The intact drug crystals were easily detected in CD4+ T cells and macrophages, the natural viral target cells, by flow cytometry and ultraperformance liquid chromatography tandem mass spectrometry. We conclude that AIE can be harnessed to monitor cell biodistribution of selective antiretroviral drug nanocrystals. • Rilpivirine (RPV) demonstrates aggregation-induced emission. • RPV nanocrystals are produced by a combination of bottom up plus top down methods. • Single-crystal x-ray crystallography data reveal CH-π interactions leading to restricted intramolecular rotations. • RPV nanocrystals are observed in CD14+ macrophages and CD4+ T-cells as detected by confocal microscopy. • Nanoparticle tracking is operative in human immunodeficiency virus infectious reservoirs. [ABSTRACT FROM AUTHOR]

The enzyme geranylgeranyl diphosphate synthase (GGDPS) is a potential therapeutic target for multiple myeloma. Malignant plasma cells produce and secrete large amounts of monoclonal protein, and inhibition of GGDPS results in disruption of protein geranylgeranylation which in turn impairs intracellular protein trafficking. Our previous work has demonstrated that some isoprenoid triazole bisphosphonates are potent and selective inhibitors of GGDPS. To explore the possibility of selective delivery of such compounds to plasma cells, new analogues with an ω-hydroxy group have been synthesized and examined for their enzymatic and cellular activity. These studies demonstrate that incorporation of the ω-hydroxy group minimally impairs GGDPS inhibitory activity. Furthermore conjugation of one of the novel ω-hydroxy GGDPS inhibitors to hyaluronic acid resulted in enhanced cellular activity. These results will allow future studies to focus on the in vivo biodistribution of HA-conjugated GGDPS inhibitors. [ABSTRACT FROM AUTHOR]