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This work describes the discovery of a bead-bound membrane-active peptide (MAP), LBF127, that selectively binds fungal giant unilamellar vesicles (GUVs) over mammalian GUVs. LBF127 was re-synthesized in solution form and demonstrated to have antifungal activity with limited hemolytic activity and cytotoxicity against mammalian cells. Through systematic structure-activity relationship studies, including N- and C-terminal truncation, alanine-walk, and d-amino acid substitution, an optimized peptide, K-oLBF127, with higher potency, less hemolytic activity, and cytotoxicity emerged. Compared to the parent peptide, K-oLBF127 is shorter by three amino acids and has a lysine at the N-terminus to confer an additional positive charge. K-oLBF127 was found to have improved selectivity toward the fungal membrane over mammalian membranes by 2-fold compared to LBF127. Further characterizations revealed that, while K-oLBF127 exhibits a spectrum of antifungal activity similar to that of the original peptide, it has lower hemolytic activity and cytotoxicity against mammalian cells. Mice infected with

General methods for library synthesis Table S1. MS and purity for cyclic peptide 1 derivatives Synthesis of focused libraries Table S2. Amino acids used in the synthesis of focused Library 1 and 2 Table S3. Amino acids used in the synthesis of focused Library 1. Table S4. Amino acids used in the synthesis of focused Library 2 NMR study of peptide 1 and 4 Experimental Constraints and Structure Calculation Table S5. Chemical shifts of peptide 1 at 295K, DMSO-d6. Table S6. Chemical shifts of peptide 4 at 295K, DMSO-d6. Table S7. Structure statistics for the ensembles of 15 calculated structures of peptide 1 and peptide 4 Figure S1. Representative regions of the 2D NOESY spectrum of 1 and 4. Figure S2. Superimposed solution structures are the ensembles of 15 structures for peptide 1 and 4. In vivo and ex vivo optical imaging Abbreviations Reference

Purpose: The majority of patients with prostate cancer who are treated with androgen-deprivation therapy (ADT) will eventually develop fatal metastatic castration-resistant prostate cancer (mCRPC). Currently, there are no effective durable therapies for patients with mCRPC. High expression of galectin-1 (Gal-1) is associated with prostate cancer progression and poor clinical outcome. The role of Gal-1 in tumor progression is largely unknown. Here, we characterized Gal-1 functions and evaluated the therapeutic effects of a newly developed Gal-1 inhibitor, LLS30, in mCRPC.Experimental Design: Cell viability, colony formation, migration, and invasion assays were performed to examine the effects of inhibition of Gal-1 in CRPC cells. We used two human CRPC xenograft models to assess growth-inhibitory effects of LLS30. Genome-wide gene expression analysis was conducted to elucidate the effects of LLS30 on metastatic PC3 cells.Results: Gal-1 was highly expressed in CRPC cells, but not in androgen-sensitive cells. Gal-1 knockdown significantly inhibited CRPC cells' growth, anchorage-independent growth, migration, and invasion through the suppression of androgen receptor (AR) and Akt signaling. LLS30 targets Gal-1 as an allosteric inhibitor and decreases Gal-1–binding affinity to its binding partners. LLS30 showed in vivo efficacy in both AR-positive and AR-negative xenograft models. LLS30 not only can potentiate the antitumor effect of docetaxel to cause complete regression of tumors, but can also effectively inhibit the invasion and metastasis of prostate cancer cells in vivo.Conclusions: Our study provides evidence that Gal-1 is an important target for mCRPC therapy, and LLS30 is a promising small-molecule compound that can potentially overcome mCRPC. Clin Cancer Res; 24(17); 4319–31. ©2018 AACR.

Increasing literature suggests that cell adhesion molecule α4β1 integrin plays a pivotal role in autoimmune diseases and cancer development. Noninvasive visualization of α4β1 integrin in vivo will facilitate the understanding of its involvement in disease progression and development of targeted therapies. Due to the lack of high-affinity targeting ligands, molecular imaging of α4β1 integrin is much less explored than that of αvβ3 and αvβ5 integrins. We have recently reported using the one bead–one compound combinatorial library method to identify a peptidomimetic, LLP2A, that preferentially binds to activated α4β1 integrin. Here, we described the use of LLP2A-Cy5.5 conjugate as an in vivo optical imaging probe in a human lymphoma xenograft model. This univalent LLP2A-Cy5.5 conjugate retained the binding activity and specificity to α4β1 integrin as shown by cell binding assays using α4β1-positive Molt-4 T-leukemia cells. The subcutaneous Molt-4 tumor was clearly visualized from 1 to 24 h after tail vein injection of the conjugate. Direct imaging and confocal microscopic examination of excised tumors and organs confirmed the accumulation of LLP2A in tumors and revealed very little or no uptake in normal organs except for lymph nodes. Kidney uptake was high when the whole organ was scanned but it was negative when examined microscopically, suggesting that LLP2A bound to the renal tubules loosely. Tumor uptake of LLP2A-Cy5.5 conjugate was blocked by excess unlabeled LLP2A. This study showed that the combinatorial chemical library-derived peptidomimetic LLP2A can be easily developed into an optical imaging probe for noninvasively monitoring of activated α4β1 integrin in vivo. [Mol Cancer Ther 2008;7(2):432–7]

Supplementary tables

Supplementary Methods from In vivo optical imaging of human lymphoma xenograft using a library-derived peptidomimetic against α4β1 integrin

The αvβ3 integrin, expressed on the surface of various normal and cancer cells, is involved in numerous physiologic processes such as angiogenesis, apoptosis, and bone resorption. Because this integrin plays a key role in angiogenesis and metastasis of human tumors, αvβ3 integrin ligands are of great interest to advances in targeted therapy and cancer imaging. In this report, one-bead one-compound (OBOC) combinatorial libraries containing the arginine-glycine-aspartic acid (RGD) motif were designed and screened against K562 myeloid leukemia cells that had been transfected with the human αvβ3 integrin gene. Cyclic peptide LXW7 was identified as a leading ligand with a built-in handle that binds specifically to αvβ3 and showed comparable binding affinity (IC50 = 0.68 ± 0.08 μmol/L) to some of the well-known RGD “head-to-tail” cyclic pentapeptide ligands reported in the literature. The biotinylated form of LXW7 ligand showed similar binding strength as LXW7 against αvβ3 integrin, whereas biotinylated RGD cyclopentapeptide ligands revealed a 2- to 8-fold weaker binding affinity than their free forms. LXW7 was able to bind to both U-87MG glioblastoma and A375M melanoma cell lines, both of which express high levels of αvβ3 integrin. In vivo and ex vivo optical imaging studies with the biotinylated ligand/streptavidin-Cy5.5 complex in nude mice bearing U-87MG or A375M xenografts revealed preferential uptake of biotinylated LXW7 in tumor. When compared with biotinylated RGD cyclopentapeptide ligands, biotinylated LXW7 showed higher tumor uptake but lower liver uptake. Mol Cancer Ther; 9(10); 2714–23. ©2010 AACR.

Supplementary materials and methods

Supplementary Data from The Use of One-Bead One-Compound Combinatorial Library Technology to Discover High-Affinity αvβ3 Integrin and Cancer Targeting Arginine-Glycine-Aspartic Acid Ligands with a Built-in Handle

Supplementary Figures

In the tumor micro-environment, tumor associated macrophages (TAMs) represent a predominant component of the total tumor mass, and TAMs play a complex and diverse role in cancer pathogenesis with potential for either tumor suppressive, or tumor promoting biology. Thus, understanding macrophage localization and function are essential for cancer diagnosis and treatment. Typically, tissue biopsy is used to evaluate the density and polarization of TAMs, but provides a limited "snapshot" in time of a dynamic and potentially heterogeneous tumor immune microenvironment. Imaging has the potential for three-dimensional mapping; however, there is a paucity of macrophage-targeted contrast agents to specifically detect TAM subtypes. We have previously found that sulfated-dextran coated iron oxide nanoparticles (SDIO) can target macrophage scavenger receptor A (SR-A, also known as CD204). Since CD204 (SR-A) is considered a biomarker for the M2 macrophage polarization, these SDIO might provide M2-specific imaging probes for MRI. In this work, we investigate whether SDIO can label M2-polarized cells

In response to the increasing manufacturing complexity/cost in maintaining DRAM advancements through traditional scaling, three-dimensional integrated circuits (3D ICs) and 2.5-dimensional ICs with Si interposers are known as promising candidates to overcome these challenges due to their advantages of low power, small form factor, high density, and high bandwidth. In this work, we present a true process-heterogeneous stacked embedded DRAM (SeDRAM) using hybrid bonding 3D integration process, achieving high bandwidth of 34 GBps/Gbit and high energy efficiency of 0.88 pJ/bit. Moreover, the critical factors of the SeDRAM design are presented (e.g., the low data movement energy, high-density physical interface, simplified protocol definition, process compatibility, density extensibility, and hybrid bonding connection fast test by DFT (design for test). Our results and design methodology have paved the way to realize applications of hybrid bonding to high bandwidth and energy efficiency DRAM. More importantly, the SeDRAM solution can also support the maximum storage density of 48 Gbit and the bandwidth capability of TBps. It can greatly alleviate the “memory wall” problem and thus improve its competitiveness in near-memory computing/computing-in-memory fields.

This study theoretically demonstrated the oxygen vacancy (VO2+)-based modulation of a tunneling junction memristor (TJM) with a high and tunable tunneling electroresistance (TER) ratio. The tunneling barrier height and width are modulated by the VO2+-related dipoles, and the ON and OFF-state of the device are achieved by the accumulation of VO2+ and negative charges near the semiconductor electrode, respectively. Furthemore, the TER ratio of TJMs can be tuned by varying the density of the ion dipoles (Ndipole), thicknesses of ferroelectric-like film (TFE) and SiO2 (Tox), doping concentration (Nd) of the semiconductor electrode, and the workfunction of the top electrode (TE). An optimized TER ratio can be achieved with high oxygen vacancy density, relatively thick TFE, thin Tox, small Nd, and moderate TE workfunction.

Hf0.5Zr0.5O2 (HZO)-based ferroelectric field-effect transistors (FeFETs) with HfO2 seed layer were investigated for radiation-hard nonvolatile memory applications. First, it was found that the HZO thin films grown on HfO2 seed layer showed improved crystallinity and ferroelectricity compared with those directly grown on SiO2 thin film, leading to a larger memory window (MW), better endurance, and retention properties of the HZO-based FeFETs with HfO2 seed layers. Moreover, after 1 Mrad(Si) 60Co $\gamma $ -ray irradiation, the memory properties of the HZO-based FeFETs with HfO2 seed layer were also better than those without the HfO2 seed layer. Especially, the HZO-based FeFETs with an HfO2 seed layer have a larger remaining MW (0.66 V) than that (0.29 V) of the FeFETs without an HfO2 seed layer after $1\times 10^{4}$ program/erase cycle. This work represents a first attempt to realize the high performances of radiation-hard HfO2-based FeFETs.

Human serum albumin (HSA) is the most abundant protein in human blood plasma. It plays a critical role in the native transportation of numerous drugs, metabolites, nutrients, and small molecules. HSA has been successfully used clinically as a noncovalent carrier for insulin (e.g., Levemir), GLP-1 (e.g., Liraglutide), and paclitaxel (e.g., Abraxane). Site-specific bioconjugation strategies for HSA only would greatly expand its role as the biocompatible, non-toxic platform for theranostics purposes. Using the enabling one-bead one-compound (OBOC) technology, we generated combinatorial peptide libraries containing myristic acid, a well-known binder to HSA at Sudlow I and II binding pockets, and an acrylamide. We then used HSA as a probe to screen the OBOC myristylated peptide libraries for reactive affinity elements (RAEs) that can specifically and covalently ligate to the lysine residue at the proximity of these pockets. Several RAEs have been identified and confirmed to be able to conjugate to HSA covalently. The conjugation can occur at physiological pH and proceed with a high yield within 1 h at room temperature. Tryptic peptide profiling of derivatized HSA has revealed two lysine residues (K225 and K414) as the conjugation sites, which is much more specific than the conventional lysine labeling strategy with N-hydroxysuccinimide ester. The RAE-driven site-specific ligation to HSA was found to occur even in the presence of other prevalent blood proteins such as immunoglobulin or whole serum. Furthermore, these RAEs are orthogonal to the maleimide-based conjugation strategy for Cys34 of HSA. Together, these attributes make the RAEs the promising leads to further develop in vitro and in vivo HSA bioconjugation strategies for numerous biomedical applications.

Immune checkpoint blockade (ICB) therapy has revolutionized clinical oncology. However, the efficacy of ICB therapy is limited by the ineffective infiltration of T effector (Teff) cells to tumors and the immunosuppressive tumor microenvironment (TME). Here, we report a programmable tumor cells/Teff cells bispecific nano-immunoengager (NIE) that can circumvent these limitations to improve ICB therapy. The peptidic nanoparticles (NIE-NPs) bind tumor cell surface α3β1 integrin and undergo in situ transformation into nanofibrillar network nanofibers (NIE-NFs). The prolonged retained nanofibrillar network at the TME captures Teff cells via the activatable α4β1 integrin ligand and allows sustained release of resiquimod for immunomodulation. This bispecific NIE eliminates syngeneic 4T1 breast cancer and Lewis lung cancer models in mice, when given together with anti-PD-1 antibody. The in vivo structural transformation-based supramolecular bispecific NIE represents an innovative class of programmable receptor-mediated targeted immunotherapeutics to greatly enhance ICB therapy against cancers.

An amorphous ZrO2 based tunneling junction memristor (TJM) with a tunneling electroresistance (TER) ratio above 400 is demonstrated. It is attributed to the modulation of tunneling barrier width induced by the accumulation of oxygen vacancies ( $V_{O}^{+}$ ) and negative charges near the ZrO2/semiconductor interface. The ferroelectric-like behaviors attributed to the voltage-modulated switching of the dipoles consisting of $V_{O}^{+}$ and negative charges in ZrO2 are characterized by a polarization-voltage test. The ZrO2 TJM achieves a TER ratio above 400 under 2.5/–1.5 V at 100 ns write/erase pulse condition, over 104 cycles program/erase endurance, and >104 s data retention.

We experimentally demonstrate ferroelectric-like non-volatile field-effect transistor (NVFET) with the amorphous Al2O3 gate insulator for artificial synapse applications. The switchable polarization (P) is attributed to the voltage modulation of mobile ions in the gate insulator. The ferroelectric-like NVFETs integrated with 3 nm and 6 nm-thick Al2O3 dielectrics demonstrate the capability to mimic various synaptic behaviors including long-term potentiation (LTP), long-term depression (LTD), and spike-timing-dependent plasticity (STDP), under different types of electrical stimuli to the gate electrode. To verify the application of the ferroelectric-like transistors in the Spike Neural Network (SNN), the online training has been carried out based on the synaptic characteristics of the devices, and a decent accuracy (>80%) is achieved for fixed-amplitude ±3 V/100 ns potentiation/depression pulses.

Exploring the high-performance non-volatile memories for realizing energy-efficient memory in complementary metal–oxide–semiconductor (CMOS) circuits, memory-in-computing, and the artificial synapse is the key to the rapid growth in data markets. One of the significant aspects is the development of non-volatile field-effect transistor (NVFET), which possesses the advantage of decoupling the “write” and “read” functions using the third terminal. In this work, building on a semiconductor channel integrated with an amorphous Al2O3 gate insulator, we report a ferroelectric-like NVFET memory and analog synapse that differ from those utilizing polycrystalline-doped HfO2 films. Switchable polarization ( ${P}$ ) is demonstrated in TaN/Al2O3/TaN, TaN/Al2O3/Si, and TaN/Al2O3/Ge stacks, which is attributed to the voltage-modulation of the oxygen vacancy and negative charge dipoles in gate insulator. A TaN/Al2O3/Ge capacitor achieves over 1010 cycles endurance of polarization-voltage measurement. A memory window (MW) of 0.85 V is obtained in the NVFET integrated with Al2O3 insulator under ±3 V at 100 ns program/erase (P/E) condition, and the P/E voltage can be reduced to ±1.6 V. A NVFET analog synapse is demonstrated to have a dynamic range above 100 [asymmetry ( $\vert \alpha _{p} - \alpha _{d} \vert $ )< 0.1] with ±2 V/100 ns potentiation/depression pulses. These results can be extended universally to other amorphous oxides and show promise for 3-D (fin-shaped) NVFETs with very small fin pitch.

Non-volatile field-effect transistor (FET) with amorphous Al2O3 dielectric is demonstrated on Si substrate, which is enabled by the voltage modulation of the oxygen vacancy and negative charge dipoles in gate insulator. Ferroelectric-like behavior in TaN/Al2O3/Si0.70Ge0.30 stacks with different thicknesses of Al2O3 is proved by polarization-voltage tests, positive-up and negative-down tests, piezoresponse force microscopy, and electrical measurements. The Al2O3 capacitors attain over 108 cycles’ endurance of polarization versus voltage measurement. A 6.5 nm-thick Al2O3 non-volatile FET achieves a memory window above 0.6 V under ±2 V at 100 ns program/erase (P/E) condition, over 104 cycles P/E endurance, and >105s data retention at room temperature.

A novel nanocrystal-embedded-insulator (NEI) ferroelectric field-effect transistor (FeFET) is demonstrated to function as a synaptic device for analog neural network (NN) applications. The NEI layer (down to 3.6 nm in thickness) comprises ferroelectric nanocrystals embedded in amorphous Al2O3, resulting in reduced operating voltages and depolarization effects as compared to conventional doped-HfO2 films. With fixed-amplitude 100 ns potentiation/depression pulses, an NEI FeFET synapse achieves weight update with small non-linearity ( $\alpha _{p}= {0.12}$ , $\alpha _{\text {d}}= -{0.09}$ ) and asymmetry factors, advantageous for analog-style NNs with online training. A convolutional NN is designed and emulated for an MNIST dataset, projecting an online training accuracy of 92%.

Nonspecific chronic low back pain (NCLBP) is a leading contributor to disease burden worldwide, and the management of NCLBP has always been a problem. This study is designed to explore the feasibility and efficacy of m-health-based core stability exercise (CSE) combined with self-compassion training (SCT) and compare it with m-health-based CSE alone for the management of NCLBP.This study is a pilot, patient-blinded randomized controlled trial. Participants with NCLBP were randomized into an intervention group and a control group. All the participants received m-health-based CSE, but those in the intervention group also received SCT before CSE. The intervention took place weekly on Saturday or Sunday for 4 weeks in total. Patients self-assessed their outcomes by filling out electronic questionnaires at 4 and 16 weeks after the start of the study. The primary outcome metrics for these questionnaires were back pain disability (based on the Roland-Morris Disability Questionnaire, RMDQ) and Pain intensity (Numeric Rating Scale, NRS; current pain, worst pain, average pain). The secondary outcome metrics were anxiety (GAD-7,7-item Generalized Anxiety Disorder scale), Depression Symptoms (PHQ-9,Patient Health Questionnaire-9), pain catastrophizing (PCS, Pain Catastrophizing Scale) and Self-efficiency (PSEQ, Pain Self-Efficiency Questionnaire).A total of 37 patients comprising 28 (75.7%) females completed the study, with 19 patients in the intervention group and 18 in the control group. The mean (SD) patient age was 35.2 (11.1) years. For all primary outcomes, although there were no significant differences between groups, we found that participants in the intervention group improved function and pain earlier. The RMDQ score changed by - 1.771 points (95% CI - 3.768 to 0.227) from baseline to 4 weeks in the control group and by - 4.822 points (95% CI - 6.752 to - 2.892) in the intervention group (difference between groups, - 3.052 [95% CI - 5.836 to - 0.267]). Also, the RMDQ score changed by - 3.328 points (95% CI - 5.252 to - 1.403) from baseline to 16 weeks in the control group and by - 5.124 points (95% CI - 7.014 to - 3.233) in the intervention group (difference between groups - 1.796 [95% CI - 4.501 to 0.909]). A similar pattern was found in the NRS scores. For secondary outcomes, the intervention group was superior to the control group in for GAD-7 (intervention difference from CSE along at week 16, - 2.156 [95% CI - 4.434 to - 0.122; P value for group effect was 0.030]). At the end of treatment, the improvement in PCS in the intervention group was significant (difference in PCS score at week 4, - 6.718 [95% CI - 11.872 to - 1.564]). We also found significant changes in PCS in the control group (- 6.326 [95% CI, - 11.250 to - 1.401]) at the 16-week follow-up. As for PSEQ, there were no apparent differences between the two groups. There were no adverse events relented to study participation.The pilot study is feasible to deliver, and our results indicate that participants in the group of m-health-based CSE combined with SCT may experience faster relief from pain intensity and back disability than those in the group of m-health-based CSE alone.ChiCTR2100042810.The impact of chronic low back pain on people’s life quality and social economy is increasing year by year. Helping patients self-manage low back pain through a biological-psycho-social model seems to be an effective management approach, but the lack of connectivity between disciplines limits the development of multidisciplinary collaboration. Mindfulness-related therapy (self-compassion training) has been proven to be effective in chronic pain, and exercise therapy is widely used in rehabilitation medicine. In this study, these two programs were combined. We also used mobile health technology in the study, which brings a lot of convenience for research. The results of the study showed that the efficacy of the combined group seemed to be more obvious and worthy of further study.

Immune checkpoint blockade (ICB) therapy has revolutionized clinical oncology. However, the efficacy of ICB therapy is limited by the ineffective homing of T effector (Teff) cells to tumours and the immunosuppressive tumour microenvironment (TME). Here, we report a programmable tumour cells/Teff cells bispecific nano-immuno-engager (NIE) that can circumvent these limitations to improve ICB therapy. We have developed 28 nm non-toxic peptidic micellar nanoparticles (NIE-NPs) that bind α3β1 integrin on tumour cells membrane and undergo in situ transformation on surface of tumour cells into nanofibrillar network (NIE-NFs). The nanofibrillar network persistently facilitates cytotoxic T cells’ homing to the proximity of tumour cells via activatable α4β1 integrin ligands, and also allows sustained release of resiquimod to reprogram the TME. This bispecific NIE eliminates syngeneic 4T1 breast cancer and Lewis lung cancer models in mice, when given together with anti-PD-1 antibody. The in vivo structural transformation-based supramolecular bispecific NIE represents an innovative class of programmable receptor-mediated targeted immunotherapeutics to greatly enhance ICB therapy against cancers.

Low dose non-toxic disulfide cross-linked micelle (DCM) encapsulated paclitaxel (PTX) was found to be highly efficacious as a radiosensitizer against oral cancer preclinical model. Intensity-modulated radiation therapy was locally administered for three consecutive days 24h after intravascular injection of DCM-[PTX] at 5mg/kg PTX. DCM-[PTX] NPs combined with conventional radiotherapy (2Gy) resulted in a 1.7-fold improvement in therapeutic efficacy compared to conventional PTX plus radiotherapy. Interestingly, we found that radiotherapy can decrease tight junctions and increase the accumulation of DCM-[PTX] in tumor sites. Stereotactic body radiotherapy (SBRT) given at 6Gy was used to further investigate the synergistic anti-tumor effect. Tumor tissues were collected to analyze the relationship between the time interval after SBRT and the biodistribution of the nanomaterials. Compared to combination DCM-[PTX] with conventional radiation dose, combination DCM-PTX with SBRT was found to be more efficacious in inhibiting tumor growth.

We demonstrate a non-volatile field-effect transistor (NVFET) with a 3-nm amorphous HfO2 dielectric that can simulate the synaptic functions under the difference and repetition of gate voltage (VG) pulses. Under 100 ns write/erase (W/E) pulse, a memory window greater than 0.56 V and cycling endurance above 106 are obtained. The storied information as short-term plasticity (STP) in the device has a spiking post-synaptic drain current (ID) that is a response to the VG input pulse and spontaneous decay of ID. A refractory period after the stimuli is observed, during which the ID hardly varies with the VG well-emulating the bio-synapse behavior. Short-term memory to long-term memory transition, paired-pulse facilitation, and post-tetanic potentiation are realized by adjusting the VG pulse waveform and number. The experimental results indicate that the amorphous HfO2 NVFET is a potential candidate for artificial bio-synapse applications.

Self-assembling peptides have shown tremendous potential in the fields of material sciences, nanoscience, and medicine. Because of the vast combinatorial space of even short peptides, identification of self-assembling sequences remains a challenge. Herein, we develop an experimental method to rapidly screen a huge array of peptide sequences for self-assembling property, using the one-bead one-compound (OBOC) combinatorial library method. In this approach, peptides on beads are N-terminally capped with nitro-1,2,3-benzoxadiazole, a hydrophobicity-sensitive fluorescence molecule. Beads displaying self-assembling peptides would fluoresce under aqueous environment. Using this approach, we identify eight pentapeptides, all of which are able to self-assemble into nanoparticles or nanofibers. Some of them are able to interact with and are taken up efficiently by HeLa cells. Intracellular distribution varied among these non-toxic peptidic nanoparticles. This simple screening strategy has enabled rapid identification of self-assembling peptides suitable for the development of nanostructures for various biomedical and material applications., Self-assembling peptides have a range of potential applications but developing self-assembling sequences can be challenging. Here, the authors report on a one-bead one-compound combinatorial library where fluorescence is used to detect the potential for self-assembly and identified candidates are evaluated.