Targeted care navigation to reduce hospital readmissions in 'at-risk' patients.

BACKGROUND: Care navigation is commonly used to reduce preventable hospitalisation. The use of Electronic Health Record-derived algorithms may enable better targeting of this intervention for greater impact. AIMS: To evaluate if community-based Targeted Care Navigation, supported by an Electronic Health Record-derived readmission risk algorithm, is associated with reduced rehospitalisation. METHODS: A propensity score matching cohort (5 comparison to 1 intervention cohort ratio) study was conducted in an 850-bed Victorian public metropolitan health service, Australia, from May to November 2017. Admitted acute care patients with a non-surgical condition, identified as at-risk of hospital readmission using an Electronic Health Record-derived readmission risk algorithm provide by the state health department, were eligible. Targeted Care Navigation involved telephone follow-up support provided for 30 days post-discharge by a registered nurse. The hazard ratio for hospital readmission was calculated at 30, 60 and 90 days post-discharge using multivariable Cox Proportional Hazards regression. RESULTS: Sixty-five recipients received care navigation and were matched to 262 people who did not receive care navigation. Excellent matching was achieved with standardised differences between groups being <0.1 for all 11 variables included in the propensity score, including the readmission risk score. The Targeted Care Navigation group had a significantly reduced hazard of readmission at 30 days (hazard ratio 0.34; 95% confidence interval: 0.12, 0.94) compared with the comparison group. The effect size was reduced at 60 and 90 days post-discharge. CONCLUSION: We provide preliminary evidence that Targeted Care Navigation supported by an Electronic Health Record-derived readmission risk algorithm may reduce 30-day hospital readmissions.

Impact of COVID-19 lockdowns on hospital presentations and admissions in the context of low community transmission: evidence from time series analysis in Melbourne, Australia.

BACKGROUND: Melbourne, Australia, successfully halted exponential transmission of COVID-19 via two strict lockdowns during 2020. The impact of such restrictions on healthcare-seeking behaviour is not comprehensively understood, but is of global importance. We explore the impact of the COVID-19 pandemic on acute, subacute and emergency department (ED) presentations/admissions within a tertiary, metropolitan health service in Melbourne, Australia, over two waves of community transmission (1 March to 20 September 2020). METHODS: We used 4 years of historical data and novel forecasting methods to predict counterfactual hospital activity for 2020, assuming absence of COVID-19. Observed activity was compared with forecasts overall, by age, triage category and for myocardial infarction and stroke. Data were analysed for all patients residing in the health service catchment area presenting between 4 January 2016 and 20 September 2020. RESULTS: ED presentations (n=401 805), acute admissions (n=371 723) and subacute admissions (n=15 676) were analysed. Substantial departures from forecasted presentation levels were observed during both waves in the ED and acute settings, and during the second wave in subacute. Reductions were most marked among those aged >80 and <18 years. Presentations persisted at expected levels for urgent conditions, and ED triage categories 1 and 5, with clear reductions in categories 2-4. CONCLUSIONS: Our analyses suggest citizens were willing and able to present with life-threatening conditions during Melbourne's lockdowns, and that switching to telemedicine did not cause widespread spill-over from primary care into ED. During a pandemic, lockdowns may not inhibit appropriate hospital attendance where rates of infectious disease are low.

Tumor-penetrating therapy for ß5 integrin-rich pancreas cancer.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by marked desmoplasia and drug resistance due, in part, to poor drug delivery to extravascular tumor tissue. Here, we report that carcinoma-associated fibroblasts (CAFs) induce ß5 integrin expression in tumor cells in a TGF-ß dependent manner, making them an efficient drug delivery target for the tumor-penetrating peptide iRGD. The capacity of iRGD to deliver conjugated and co-injected payloads is markedly suppressed when ß5 integrins are knocked out in the tumor cells. Of note, ß5 integrin knock-out in tumor cells leads to reduced disease burden and prolonged survival of the mice, demonstrating its contribution to PDAC progression. iRGD significantly potentiates co-injected chemotherapy in KPC mice with high ß5 integrin expression and may be a powerful strategy to target an aggressive PDAC subpopulation.

Antibiotic-loaded nanoparticles targeted to the site of infection enhance antibacterial efficacy.

Bacterial resistance to antibiotics has made it necessary to resort to antibiotics that have considerable toxicities. Here, we show that the cyclic 9-amino acid peptide CARGGLKSC (CARG), identified via phage display on Staphylococcus aureus (S. aureus) bacteria and through in vivo screening in mice with S. aureus-induced lung infections, increases the antibacterial activity of CARG-conjugated vancomycin-loaded nanoparticles in S. aureus-infected tissues and reduces the needed overall systemic dose, minimizing side effects. CARG binds specifically to S. aureus bacteria but not Pseudomonas bacteria in vitro, selectively accumulates in S. aureus-infected lungs and skin of mice but not in non-infected tissue and Pseudomonas-infected tissue, and significantly enhances the accumulation of intravenously injected vancomycin-loaded porous silicon nanoparticles bearing the peptide in S. aureus-infected mouse lung tissue. The targeted nanoparticles more effectively suppress staphylococcal infections in vivo relative to equivalent doses of untargeted vancomycin nanoparticles or of free vancomycin. The therapeutic delivery of antibiotic-carrying nanoparticles bearing peptides targeting infected tissue may help combat difficult-to-treat infections.

Graphene biointerfaces for optical stimulation of cells.

Noninvasive stimulation of cells is crucial for the accurate examination and control of their function both at the cellular and the system levels. To address this need, we present a pioneering optical stimulation platform that does not require genetic modification of cells but instead capitalizes on unique optoelectronic properties of graphene, including its ability to efficiently convert light into electricity. We report the first studies of optical stimulation of cardiomyocytes via graphene-based biointerfaces (G-biointerfaces) in substrate-based and dispersible configurations. The efficiency of stimulation via G-biointerfaces is independent of light wavelength but can be tuned by changing the light intensity. We demonstrate that an all-optical evaluation of use-dependent drug effects in vitro can be enabled using substrate-based G-biointerfaces. Furthermore, using dispersible G-biointerfaces in vivo, we perform optical modulation of the heart activity in zebrafish embryos. Our discovery is expected to empower numerous fundamental and translational biomedical studies.

Screening for canine transitional cell carcinoma (TCC) by SERS-based quantitative urine cytology.

Canine lower urinary tract neoplasia is a clinically important disease process that has high mortality due to late stage diagnosis and poorly durable response to treatment. Non-invasive diagnostic techniques (e.g. dipstick test, urine cytology) currently have poor diagnostic value, while more invasive tests (e.g. cystoscopy and biopsy) are costly and often require general anesthesia. We have developed and herein describe a quantitative cytological analysis method based on the use of surface-enhanced Raman spectroscopy (SERS), for identifying cancerous transitional cells in urine using SERS biotags (SBTs) carrying the peptide PLZ4 (amino acid sequence cQDGRMGFc) that targets malignant transitional cells. By analyzing the ratio of the PLZ4-SBTs to an on board control we were able to show that transitional cells had significantly higher ratios (P < 0.05) in patients diagnosed with transitional cell carcinoma (TCC) than in healthy samples.

Publisher Correction: Identification of a peptide recognizing cerebrovascular changes in mouse models of Alzheimer's disease.

The original version of the Supplementary Information associated with this Article inadvertently omitted Supplementary Table 1. The HTML has now been updated to include a corrected version of the Supplementary Information.

Identification of a peptide recognizing cerebrovascular changes in mouse models of Alzheimer's disease.

Cerebrovascular changes occur in Alzheimer's disease (AD). Using in vivo phage display, we searched for molecular markers of the neurovascular unit, including endothelial cells and astrocytes, in mouse models of AD. We identified a cyclic peptide, CDAGRKQKC (DAG), that accumulates in the hippocampus of hAPP-J20 mice at different ages. Intravenously injected DAG peptide homes to neurovascular unit endothelial cells and to reactive astrocytes in mouse models of AD. We identified connective tissue growth factor (CTGF), a matricellular protein that is highly expressed in the brain of individuals with AD and in mouse models, as the target of the DAG peptide. We also showed that exogenously delivered DAG homes to the brain in mouse models of glioblastoma, traumatic brain injury, and Parkinson's disease. DAG may potentially be used as a tool to enhance delivery of therapeutics and imaging agents to sites of vascular changes and astrogliosis in diseases associated with neuroinflammation.

In vivo cation exchange in quantum dots for tumor-specific imaging.

In vivo tumor imaging with nanoprobes suffers from poor tumor specificity. Here, we introduce a nanosystem, which allows selective background quenching to gain exceptionally tumor-specific signals. The system uses near-infrared quantum dots and a membrane-impermeable etchant, which serves as a cation donor. The etchant rapidly quenches the quantum dots through cation exchange (ionic etching), and facilitates renal clearance of metal ions released from the quantum dots. The quantum dots are intravenously delivered into orthotopic breast and pancreas tumors in mice by using the tumor-penetrating iRGD peptide. Subsequent etching quenches excess quantum dots, leaving a highly tumor-specific signal provided by the intact quantum dots remaining in the extravascular tumor cells and fibroblasts. No toxicity is noted. The system also facilitates the detection of peritoneal tumors with high specificity upon intraperitoneal tumor targeting and selective etching of excess untargeted quantum dots. In vivo cation exchange may be a promising strategy to enhance specificity of tumor imaging.The imaging of tumors in vivo using nanoprobes has been challenging due to the lack of sufficient tumor specificity. Here, the authors develop a tumor-specific quantum dot system that permits in vivo cation exchange to achieve selective background quenching and high tumor-specific imaging.

Ratiometric in vivo auditioning of targeted silver nanoparticles.

Attaching affinity ligands to nanoparticles (NPs) increases selectivity for targeting cells and tissues, and can result in improved sensitivity and reduced off-target toxicity in diagnostic and therapeutic systems. The decision over key features - NP size, shape, coating strategies and targeting ligands for clinical translation is often hampered by a lack of quantitative in vivo NP homing assays. Sensitive, internally controlled assays are needed which allow for quantitative comparisons (auditions) among various formulations of targeted NPs. We recently reported the development of peptide-functionalized, isotopically-barcoded silver NPs (AgNPs) for ultrasensitive studies centered on measuring relative ratios of NP internalization into cultured cells. Here we evaluated the application of this technology for NP homing studies in live mice using peptides with previously described tissue tropism; one peptide that favors vascular beds of the normal lungs (RPARPAR; receptor neuropilin-1, or NRP-1) and another that is selective for central nervous system vessels (CAGALCY). Equimolar mixtures of the peptide-targeted Ag107-NPs and Ag109 control particles were mixed and injected intravenously. Distribution profiles of Ag107 and Ag109 in tissue extracts were determined simultaneously through inductively coupled plasma mass spectrometry (ICP-MS). Compared to non-targeted particles up to ∼9-fold increased lung accumulation was seen for RPARPAR-OH AgNPs (but not for AgNPs functionalized with RPARPAR-NH2, which does not bind to NRP-1). Similarly, AgNPs functionalized with the brain-homing CAGALCY peptide were overrepresented in brain extracts. Spatial distribution (mapping) analysis by laser ablation ICP-MS (LA-ICP-MS) was used to determine the ratio Ag107/Ag109 in tissue cryosections. The mapping demonstrated preferential accumulation of the RPARPAR-AgNPs in the perivascular areas around pulmonary veins, and CAGALCY AgNPs accumulated in discrete areas of the brain (e.g. in the vessels of cerebellar fibrillary tracts). Based on these results, the internally controlled ratiometric AgNP system is suitable for quantitative studies of the effect of targeting ligands on NP biodistribution, at average tissue concentration and distribution at the microscopic level. The platform might be particularly relevant for target sites with high local variability in uptake, such as tumors.

Porous Silicon Nanoparticle Delivery of Tandem Peptide Anti-Infectives for the Treatment of Pseudomonas aeruginosa Lung Infections.

There is an urgent need for new materials to treat bacterial infections. In order to improve antibacterial delivery, an anti-infective nanomaterial is developed that utilizes two strategies for localization: i) a biodegradable nanoparticle carrier to localize therapeutics within the tissue, and ii) a novel tandem peptide cargo to localize payload to bacterial membranes. First, a library of antibacterial peptides is screened that combines a membrane-localizing peptide with a toxic peptide cargo and discovers a tandem peptide that displays synergy between the two domains and is able to kill Pseudomonas aeruginosa at sub-micromolar concentrations. To apply this material to the lung, the tandem peptide is loaded into porous silicon nanoparticles (pSiNPs). Charged peptide payloads are loaded into the pores of the pSiNP at ≈30% mass loading and ≈90% loading efficiency using phosphonate surface chemistry. When delivered to the lungs of mice, this anti-infective nanomaterial exhibits improved safety profiles over free peptides. Moreover, treatment of a lung infection of P. aeruginosa results in a large reduction in bacterial numbers and markedly improves survival compared to untreated mice. Collectively, this study presents the selection of a bifunctional peptide-based anti-infective agent and its delivery via biodegradable nanoparticles for application to an animal model of lung infection.

Early experience of a new extracorporeal carbon dioxide removal device for acute hypercapnic respiratory failure.

BACKGROUND: Recent advances in the technology of extracorporeal respiratory assist systems have led to a renewed interest in extracorporeal carbon dioxide removal (ECCOR). The Hemolung is a new, low-flow, venovenous, minimally invasive, partial ECCOR device that has recently been introduced to clinical practice to aid in avoiding invasive ventilation or to facilitate lung-protective ventilation. OBJECTIVE: We report our early experience on use, efficacy and safety of the Hemolung in three Australian intensive care units. METHODS: Retrospective review of all patients with acute or acute-on-chronic respiratory failure (due to chronic obstructive pulmonary disease [COPD] with severe hypercapnic respiratory failure when non-invasive ventilation failed; acute respiratory distress syndrome; COPD; or asthma when lung-protective ventilation was not feasible due to hypercapnia) for whom the Hemolung was used. RESULTS: Fifteen patients were treated with ECCOR. In four out of five patients, the aim of avoiding intubation was achieved. In the remaining 10 patients, the strategy of instituting lung-protective ventilation was successful. The median duration for ECCOR was 5 days (interquartile range, 3-7 days). The pH and PCO2 improved significantly within 6 hours of instituting ECCOR, in conjunction with a significant reduction in minute ventilation. The CO2 clearance was 90-100 mL/min. A total of 93% of patients survived to weaning from ECCOR, 73% survived to ICU discharge and 67% survived to hospital discharge. CONCLUSION: Our data shows that ECCOR was safe and effective in this cohort. Further experience is vital to identify the patients who may benefit most from this promising therapy.

Composite Porous Silicon-Silver Nanoparticles as Theranostic Antibacterial Agents.

A theranostic nanoparticle with biochemically triggered antibacterial activity is demonstrated. Metallic silver is deposited onto porous silicon nanoparticles (pSiNPs) by galvanic displacement. When aqueous diaminesilver ([Ag(NH3)2]+) is used as a silver source, the pSiNPs template the crystalline silver as small (mean diameter 13 nm) and well-dispersed nanoparticles embedded within and on the larger (100 nm) pSiNPs. The silver nanoparticles (AgNPs) quench intrinsic photoluminescence (PL) from the porous silicon (pSi) matrix. When exposed to an aqueous oxidant, the AgNPs are preferentially etched, Ag+ is released into solution, and PL from the pSi carrier is recovered. The released Ag+ results in 90% killing of (Gram-negative) Pseudomonas aeruginosa and (Gram-positive) Staphylococcus aureus within 3 h. When conjugated with the TAT peptide (sequence RKKRRQRRR), the silver-deposited porous silicon (pSi-Ag) nanocomposite shows distinct targeting toward S. aureus bacteria in vitro. Intravenously injected TAT-conjugated pSi-Ag nanoparticles accumulate in the liver, spleen, and lungs of mice, and the in vivo release of Ag+ and recovery of PL from pSi are demonstrated by the subsequent intraperitoneal administration of a hexacyanoferrate solution. The released Ag+ leads to a significant bacterial count reduction in liver tissue relative to the control. The data demonstrate the feasibility of the targeted and triggered delivery of antibacterial Ag+ ion in vivo, using a self-reporting and nontoxic nanocarrier.

Nanostructured Antagonist of Extrasynaptic NMDA Receptors.

Glutamatergic cytotoxicity mediated by overactivation of N-methyl-d-aspartate receptors (NMDARs) is implicated in numerous neurological disorders. To be therapeutically viable, NMDAR antagonists must preserve physiological role of synaptic NMDARs (sNMDARs) in synaptic transmission and block only excessive pathological activation of NMDARs. Here we present a novel NMDAR antagonist that satisfies this two-fold requirement by exploiting spatial differences in NMDAR subcellular locations. Specifically, we designed a hybrid nanodrug (AuM) to be larger than the synaptic cleft by attaching memantine, NMDAR antagonist, via polymer linkers to a gold nanoparticle. We show that AuM efficiently and selectively inhibited extrasynaptic NMDARs (eNMDARs), while having no effect on sNMDARs and synaptic transmission. AuM exhibited neuroprotective properties both in vitro and ex vivo during such neurotoxic insults as NMDAR-mediated cytotoxicity in cerebrocortical cell culture and oxygen-glucose deprivation in acute hippocampal slices. Furthermore, AuM prevented dendritic spine loss triggered by Aß oligomers in organotypic hippocampal slices and was more effective than free memantine. Using a novel rational design strategy, we demonstrate a proof of concept for a new class of neuroprotective drugs that might be beneficial for treatment of several neurological disorders.

Tumor-Targeted Multimodal Optical Imaging with Versatile Cadmium-Free Quantum Dots.

The rapid development of fluorescence imaging technologies requires concurrent improvements in the performance of fluorescent probes. Quantum dots have been extensively used as an imaging probe in various research areas because of their inherent advantages based on unique optical and electronic properties. However, their clinical translation has been limited by the potential toxicity especially from cadmium. Here, a versatile bioimaging probe is developed by using highly luminescent cadmium-free CuInSe2/ZnS core/shell quantum dots conjugated with CGKRK (Cys-Gly-Lys-Arg-Lys) tumor-targeting peptides. This probe exhibits excellent photostability, reasonably long circulation time, minimal toxicity, and strong tumor-specific homing property. The most important feature of this probe is that it shows distinctive versatility in tumor-targeted multimodal imaging including near-infrared, time-gated, and two-photon imaging in different tumor models. In a glioblastoma mouse model, the targeted probe clearly denotes tumor boundaries and positively labels a population of diffusely infiltrating tumor cells, suggesting its utility in precise tumor detection during surgery. This work lays a foundation for potential clinical translation of the probe.

A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries.

Traumatic brain injury (TBI) is a major health and socio-economic problem, but no pharmacological agent is currently approved for the treatment of acute TBI. Thus, there is a great need for advances in this field. Here, we describe a short peptide (sequence CAQK) identified by in vivo phage display screening in mice with acute brain injury. The CAQK peptide selectively binds to injured mouse and human brain, and systemically injected CAQK specifically homes to sites of brain injury in mouse models. The CAQK target is a proteoglycan complex upregulated in brain injuries. Coupling to CAQK increased injury site accumulation of systemically administered molecules ranging from a drug-sized molecule to nanoparticles. CAQK-coated nanoparticles containing silencing oligonucleotides provided the first evidence of gene silencing in injured brain parenchyma by systemically administered siRNA. These findings present an effective targeting strategy for the delivery of therapeutics in clinical management of acute brain injuries.

Urokinase-controlled tumor penetrating peptide.

Tumor penetrating peptides contain a cryptic (R/K)XX(R/K) CendR element that must be C-terminally exposed to trigger neuropilin-1 (NRP-1) binding, cellular internalization and malignant tissue penetration. The specific proteases that are involved in processing of tumor penetrating peptides identified using phage display are not known. Here we design de novo a tumor-penetrating peptide based on consensus cleavage motif of urokinase-type plasminogen activator (uPA). We expressed the peptide, uCendR (RPARSGR↓SAGGSVA, ↓ shows cleavage site), on phage or coated it onto silver nanoparticles and showed that it is cleaved by uPA, and that the cleavage triggers binding to recombinant NRP-1 and to NPR-1-expressing cells. Upon systemic administration to mice bearing uPA-overexpressing breast tumors, FAM-labeled uCendR peptide and uCendR-coated nanoparticles preferentially accumulated in tumor tissue. We also show that uCendR phage internalization into cultured cancer cells and its penetration in explants of murine tumors and clinical tumor explants can be potentiated by combining the uCendR peptide with tumor-homing module, CRGDC. Our work demonstrates the feasibility of designing tumor-penetrating peptides that are activated by a specific tumor protease. As upregulation of protease expression is one of the hallmarks of cancer, and numerous tumor proteases have substrate specificities compatible with proteolytic unmasking of cryptic CendR motifs, the strategy described here may provide a generic approach for designing proteolytically-actuated peptides for tumor-penetrative payload delivery.

New p32/gC1qR Ligands for Targeted Tumor Drug Delivery.

Cell surface p32, the target of LyP-1 homing peptide, is upregulated in tumors and atherosclerotic plaques and has been widely used as a receptor for systemic delivery of payloads. Here, we identified an improved LyP-1-mimicking peptide (TT1, CKRGARSTC). We used this peptide in a fluorescence polarization-based high-throughput screening of a 50,000-compound chemical library and identified a panel of compounds that bind p32 with low micromolar affinity. Among the hits identified in the screen, two compounds were shown to specifically bind to p32 in multiple assays. One of these compounds was chosen for an in vivo study. Nanoparticles surface-functionalized with this compound specifically adhered to surfaces coated with recombinant p32 and, when injected intravenously, homed to p32-expressing breast tumors in mice. This compound provides a lead for the development of p32-targeted affinity ligands that circumvent some of the limitations of peptide-based probes in guided drug delivery.

Paclitaxel-Loaded Polymersomes for Enhanced Intraperitoneal Chemotherapy.

Peritoneal carcinomatosis is present in more than 60% of gastric cancer, 40% of ovarian cancer, and 35% of colon cancer patients. It is the second most common cause of cancer-related mortality, with a median survival of 1 to 3 months. Cytoreductive surgery combined with intraperitoneal chemotherapy is the current clinical treatment, but achieving curative drug accumulation and penetration in peritoneal carcinomatosis lesions remains an unresolved challenge. Here, we used flexible and pH-sensitive polymersomes for payload delivery to peritoneal gastric (MKN-45P) and colon (CT26) carcinoma in mice. Polymersomes were loaded with paclitaxel and in vitro drug release was studied as a function of pH and time. Paclitaxel-loaded polymersomes remained stable in aqueous solution at neutral pH for up to 4 months. In cell viability assay on cultured cancer cell lines (MKN-45P, SKOV3, CT26), paclitaxel-loaded polymersomes were more toxic than free drug or albumin-bound paclitaxel (Abraxane). Intraperitoneally administered fluorescent polymersomes accumulated in malignant lesions, and immunofluorescence revealed an intense signal inside tumors with no detectable signal in control organs. A dual targeting of tumors was observed: direct (circulation-independent) penetration, and systemic, blood vessel-associated accumulation. Finally, we evaluated preclinical antitumor efficacy of paclitaxel-polymersomes in the treatment of MKN-45P disseminated gastric carcinoma using a total dose of 7 mg/kg. Experimental therapy with paclitaxel-polymersomes improved the therapeutic index of drug over free paclitaxel and Abraxane, as evaluated by intraperitoneal tumor burden and number of metastatic nodules. Our findings underline the potential utility of the polymersome platform for delivery of drugs and imaging agents to peritoneal carcinomatosis lesions. Mol Cancer Ther; 15(4); 670-9. ©2016 AACR.

Targeted silver nanoparticles for ratiometric cell phenotyping.

Affinity targeting is used to deliver nanoparticles to cells and tissues. For efficient targeting, it is critical to consider the expression and accessibility of the relevant receptors in the target cells. Here, we describe isotopically barcoded silver nanoparticles (AgNPs) as a tool for auditing affinity ligand receptors in cells. Tumor penetrating peptide RPARPAR (receptor: NRP-1) and tumor homing peptide GKRK (receptor: p32) were used as affinity ligands on the AgNPs. The binding and uptake of the peptide-functionalized AgNPs by cultured PPC-1 prostate cancer and M21 melanoma cells was dependent on the cell surface expression of the cognate peptide receptors. Barcoded peptide-functionalized AgNPs were synthesized from silver and palladium isotopes. The cells were incubated with a cocktail of the barcoded nanoparticles [RPARPAR (R), GKRK (K), and control], and cellular binding and internalization of each type of nanoparticle was assessed by inductively coupled plasma mass spectrometry. The results of isotopic analysis were in agreement with data obtained using optical methods. Using ratiometric measurements, we were able to classify the PPC-1 cell line as mainly NRP-1-positive, with 75 ± 5% R-AgNP uptake, and the M21 cell line as only p32-positive, with 89 ± 9% K-AgNP uptake. The isotopically barcoded multiplexed AgNPs are useful as an in vitro ratiometric phenotyping tool and have potential uses in functional evaluation of the expression of accessible homing peptide receptors in vivo.