Photodynamic Therapy Combined with Liquid Nitrogen Cryotherapy and Curettage for the Treatment of Recalcitrant Periungual and Subungual Warts: Clinical Experience and Literature Review.

Warts are caused by human papillomavirus (HPV) infection and can involve multiple parts of skin and mucosa, of which periungual and subungual warts are the most difficult to treat. Periungual or subungual wart is verruca vulgaris growing around or under the fingernail, destroying and deforming the nail and nail bed. Currently, liquid nitrogen cryotherapy and CO2 laser are often used for the treatment. Clinically, few doctors routinely use photodynamic therapy (PDT) to treat viral warts. We used PDT combined with liquid nitrogen cryotherapy and curettage to successfully treat a case of intractable periungual and subungual warts.

Are behavioral interventions a better choice for atopic dermatitis patients? A meta-analysis of 6 randomized controlled trials.

BACKGROUND: The treatment for atopic dermatitis (AD) has been the focus of clinical research, and behavioral intervention is considered an indispensable treatment method. To our knowledge, no relevant meta-analysis has evaluated the effects of behavioral interventions on atopic dermatitis. OBJECTIVES: To evaluate the effects of behavioral interventions on atopic dermatitis. METHODS: The authors searched PubMed, EMBASE, and Cochrane CENTRAL to retrieve relevant RCTs (up to Feb 2022). The search strategy involved a combination of related keywords. The Cochrane Q and I2 statistics were used to assess heterogeneity. RESULTS: Six RCTs involving seven reports with 246 patients were included. The results suggested that behavioral interventions could relieve eczema severity (correlation coefficient [r = -0.39]; p < 0.001) and scratching severity significantly (r = -0.19; p = 0.017), while not affect itching intensity (r = -0.02; p = 0.840). A sensitivity analysis confirmed the robustness of the results. STUDY LIMITATIONS: An important limitation of this study was the insufficient number of RCTs and the limited sample size. In addition, the study lacked a control group receiving a type of intervention other than the experimental protocol. Another limitation was the short duration of follow-up. CONCLUSIONS: This study suggests that behavioral interventions could be effective in treating atopic dermatitis by reducing eczema and scratching severity. Additionally, habit-reversal behavioral therapy may be more effective for treating atopic dermatitis.

Wound microenvironment-responsive dually cross-linked nanofibrillar peptide hydrogels for efficient hemostatic control and multi-faceted wound management.

The wound microenvironment-responsive hydrogel, featuring a dually cross-linked architecture, offers distinct advantages in the realm of drug delivery due to its exceptional mechanical properties and responsiveness to stimuli. In this investigation, a versatile dually cross-linked hydrogel was synthesized. The initial framework was established through non-covalent interactions employing a self-assembling peptide indomethacin-Gly-Phe-Phe-Tyr-Gly-Arg-Gly-Asp (abbreviated as IDM-1), while the second framework underwent chemical cross-linking of chitosan (CS) mediated by genipin. This dually-network arrangement significantly bolstered the structure, proving effective for hemostatic control. In addition, hydrogels can be triggered for degradation by proteases highly expressed in the wound microenvironment, releasing drugs like indomethacin (IDM) and CS. This characteristic introduced efficient multi-faceted wound management in vitro and in vivo, such as anti-inflammatory and antibacterial activities, ultimately augmenting the wound healing process. Thus, the development of a dually cross-linked hydrogel that enables smart drug release triggered by specific wound microenvironment presents considerable potential within the realm of wound management.

Enzyme-mediated fabrication of nanocomposite hydrogel microneedles for tunable mechanical strength and controllable transdermal efficiency.

Microneedles (MNs) are increasingly used in transdermal drug delivery due to high bioavailability, simple operation, and improved patient compliance. However, further clinical applications are hindered by unsatisfactory mechanical strength and uncontrolled drug release. Herein, an enzyme-mediated approach is reported for the fabrication of nanocomposite hydrogel-based MNs with tunable mechanical strength and controllable transdermal efficiency. As a proof-of-concept, tetrakis(1-methyl-4-pyridinio)porphyrin (TMPyP) was chosen as a model drug for photodynamic therapy of melanoma. TMPyP-loaded PLGA nanoparticles (NP/TMPyP) served as an inner phase of MNs for controlled release of photosensitizers, and enzyme-mediated hyaluronic acid-tyramine (HAT) hydrogels served as an external phase for optimizing the mechanical strength of MNs. By changing the concentration of HRP and H2O2, three types of MNs were fabricated for transdermal delivery of TMPyP, which demonstrated different cross-linking densities and various mechanical strength. Among the three MNs, the HAT-Medium@NP/TMPyP-MN with a medium mechanical strength exhibited the highest values of transdermal efficiency in vitro and the longest retention time in vivo. As compared to pure TMPyP and TMPyP-loaded nanoparticles, the HAT-Medium@NP/TMPyP-MN demonstrated higher anticancer efficacy in both melanoma A375 cells and a xenografted tumor mouse model. Therefore, the enzyme-mediated nanocomposite hydrogel MNs show great promise in the transdermal delivery of therapeutic drugs with enhanced performance. STATEMENT OF SIGNIFICANCE: This study reports an enzyme-mediated approach for the fabrication of photodynamically-active microneedles (HAT@NP/TMPyP-MNs) with tunable mechanical strength and controllable transdermal efficiency. On one hand, HAT hydrogels that bear different cross-linking densities, facilitate tunable mechanical strength and optimized transdermal performances of MNs; on the other hand, NP/TMPyP and HAT network contribute to sustained release of photosensitizers. Comparing to other formulation (i.e., NP/TMPyP or TMPyP), the HAT-Medium@NP/TMPyP-MN exhibited excelling anticancer efficacy in photodynamic therapy in vitro and in vivo. We believe that the combination of enzyme-mediated polymeric cross-linking and slow-releasing nano-vehicles in a single nanocomposite platform provides a versatile approach for the fabrication of MNs with enhanced therapeutic efficacy, which holds great promise in the transdermal delivery of various therapeutic drugs in future.

A Dual-Responsive Morphologically-Adaptable Nanoplatform for Targeted Delivery of Activatable Photosensitizers in Precision Photodynamic Therapy.

Photodynamic therapy (PDT) is an effective approach for treating melanoma. However, the photosensitizers employed in PDT can accumulate in healthy tissues, potentially causing harm to normal cells and resulting in side effects such as heightened photosensitivity. To address this, an activatable photosensitizer (PSD) by linking PpIX with a fluorescence quencher using a disulfide bond is designed. PSD responded to endogenous GSH, showing high selectivity for A375 cells. To enhance PSD's bioavailability and anticancer efficacy, an enzyme-responsive nanoplatform based on a lonidamine-derived self-assembling peptide is developed. Initially, PSD and the peptide self-assembled into nanoparticles, displaying potent tumor targeting of PSD in vivo. Upon cell uptake, these nanoparticles specifically responded to elevated cathepsin B, causing nanoparticle disintegration and releasing PSD and lonidamine prodrug (LND-1). PSD is selectively activated by GSH for cancer-specific fluorescence imaging and precision PDT, while LND-1 targeted mitochondria, forming a fibrous lonidamine depot in situ and intensifying photosensitizer's cytotoxicity through ROS generation, mitochondrial dysfunction, and DNA damage. Notably, intravenous administration of LND-1-PEG@PSD with light irradiation significantly suppressed A375-xenografted mouse tumor growth, with minimal systemic toxicity. Together, the synergy of activatable photosensitizer and enzyme-responsive nanoplatform elevates PDT precision and diminishes side effects, showcasing significant potential in the realm of cancer nanomedicine.

Peptide-containing nanoformulations: Skin barrier penetration and activity contribution.

Transdermal drug delivery presents a less invasive pathway, circumventing the need to pass through the gastrointestinal tract and liver, thereby reducing drug breakdown, initial metabolism, and gastrointestinal discomfort. Nevertheless, the unique composition and dense structure of the stratum corneum present a significant barrier to transdermal delivery. This article presents an overview of the current developments in peptides and nanotechnology to address this challenge. Initially, we sum up peptide-containing nanoformulations for transdermal drug delivery, examining them through the lenses of both inorganic and organic materials. Particular emphasis is placed on the diverse roles that peptides play within these nanoformulations, including conferring functionality upon nanocarriers and enhancing the biological efficacy of drugs. Subsequently, we summarize innovative strategies for enhancing skin penetration, categorizing them into passive and active approaches. Lastly, we discuss the therapeutic potential of peptide-containing nanoformulations in addressing a range of diseases, drawing insights from the biological activities and functions of peptides. Furthermore, the challenges hindering clinical translation are also discussed, providing valuable insights for future advancements in transdermal drug delivery.

Malnutrition Is Associated with Diabetic Retinopathy in Patients with Type 2 Diabetes.

Background: The relationship between malnutrition and diabetic retinopathy (DR) is still unclear. The purpose of this study is to investigate the relationship between malnutrition and DR in type 2 diabetic patients. Methods: A cross-sectional study was conducted on 612 patients with type 2 diabetes mellitus. Four malnutrition assessment tools: Global Leadership Initiative on Malnutrition (GLIM) criteria, controlling nutritional status (CONUT), nutritional risk index (NRI), and prognostic nutritional index (PNI), were applied to assess the nutritional status of the study population. The association between malnutrition and DR was examined using multivariable logistic regression and ordered logistic regression. Results: The proportion of malnutrition varied from 10.0% to 34.3% in total patients and from 16.3% to 45.1% in DR patients across the assessment tools. DR patients were more likely to be malnourished than patients without DR. The adjusted odds ratios (aOR) and 95% confidence interval (CI) for DR of malnutrition defined by different tools were 1.86 (1.01-3.14) for GLIM criteria, 1.67 (1.04-2.70) for NRI, and 2.24 (1.07-4.69) for PNI. The aOR and 95% CI for the severity of DR of malnutrition defined by different tools were 1.99 (1.12-3.51) for GLIM criteria, 1.65 (1.06-2.58) for NRI, and 2.51 (1.31-4.79) for PNI. Conclusions: Malnutrition was common in DR patients, and it was closely linked to the presence and severity of DR. Diabetic patients with DR should undergo nutritional assessment and early treatment of malnutrition to prevent the onset or progression of DR.

Effects of edaravone dexborneol on neurological function and serum inflammatory factor levels in patients with acute anterior circulation large vessel occlusion stroke.

The goal of this study is to evaluate and analyze the effects of edaravone (EDV) dexborneol on neurological function and serum inflammatory factor levels among patients with acute anterior circulation big artery blockage stroke. A total of 142 patients with acute anterior circulation large vessel occlusion (LVO) were randomly allocated to the study group (69 patients) or the control group (73 patients). In the study group, patients were treated with 37.5 mg EDV dexborneol twice a day for 10-14 days, based on the control group. The primary efficacy outcome was the National Institutes of Health Stroke Scale score change from baseline to 90 days and the proportion of modified Rankin Scale (mRS)score ≤1 at 90 days after randomization. The secondary outcome included the decrease in inflammatory factors at 14 days. The primary safety outcome was the incidence of hemorrhagic transformation assessed according to Heidelberg bleeding classification within 7 days. A higher percentage of patients with HIHSS score ≤5 at 90 days in the EDV dexcamphorol group was observed than in the control group (75.36% vs 64.38%; P = 0.015). A higher percentage of patients with mRS score ≤1 at 90 days in the EDV dexcamphorol group was observed than in the control group (63.77% vs 50.68%; P = 0.012). After treatment, the levels of IL-6 and hs-CRP were significantly lower following treatment and compared to the control group (P < 0.05). In patients receiving the EDV dexborneol group, a significantly decreased risk of radiographic intracranial hemorrhage was found compared with the control group (20.29% vs 39.73%; P = 0.0006). In conclusion, EDV dexborneol can improve the clinical outcomes of patients with acute anterior circulation LVO stroke, which can be used as an effective supplement to thrombectomy therapy.

Corrigendum: Genome-wide analysis of transcriptome and histone modifications in Brassica napus hybrid.

[This corrects the article DOI: 10.3389/fpls.2023.1123729.].

Diploid and tetraploid genomes of Acorus and the evolution of monocots.

Monocots are a major taxon within flowering plants, have unique morphological traits, and show an extraordinary diversity in lifestyle. To improve our understanding of monocot origin and evolution, we generate chromosome-level reference genomes of the diploid Acorus gramineus and the tetraploid Ac. calamus, the only two accepted species from the family Acoraceae, which form a sister lineage to all other monocots. Comparing the genomes of Ac. gramineus and Ac. calamus, we suggest that Ac. gramineus is not a potential diploid progenitor of Ac. calamus, and Ac. calamus is an allotetraploid with two subgenomes A, and B, presenting asymmetric evolution and B subgenome dominance. Both the diploid genome of Ac. gramineus and the subgenomes A and B of Ac. calamus show clear evidence of whole-genome duplication (WGD), but Acoraceae does not seem to share an older WGD that is shared by most other monocots. We reconstruct an ancestral monocot karyotype and gene toolkit, and discuss scenarios that explain the complex history of the Acorus genome. Our analyses show that the ancestors of monocots exhibit mosaic genomic features, likely important for that appeared in early monocot evolution, providing fundamental insights into the origin, evolution, and diversification of monocots.

Multicolor Tunable Electrochromic Materials Based on the Burstein-Moss Effect.

Inorganic electrochromic (EC) materials, which can reversibly switch their optical properties by current or potential, are at the forefront of commercialization of displays and smart windows. However, most inorganic EC materials have challenges in achieving multicolor tunability. Here, we propose that the Burstein-Moss (BM) effect, which could widen the optical gap by carrier density, could be a potential mechanism to realize the multicolor tunable EC phenomenon. Degenerated semiconductors with suitable fundament band gaps and effective carrier masses could be potential candidates for multicolor tunable EC materials based on the BM effect. We select bulk Y2CF2 as an example to illustrate multicolor tunability based on the BM effect. In addition to multicolor tunability, the BM effect also could endow EC devices with the ability to selectively modulate the absorption for near infrared and visible light, but with a simpler device structure. Thus, we believe that this mechanism could be applied to design novel EC smart windows with unprecedented functions.

Cascade-Activated AIEgen-Peptide Probe for Noninvasively Monitoring Chymotrypsin-like Activity of Proteasomes in Cancer Cells.

Noninvasive monitoring of chymotrypsin-like (ChT-L) activity of proteasomes is of great significance for the diagnosis and prognosis of various cancers. However, commercially available proteasome probes usually lack adequate cancer-cell selectivity. To noninvasively monitor ChT-L activity of proteasomes in living cells, we rationally designed a cascade-activated AIEgen-peptide probe (abbreviated as TPE-1p), which self-assembled in aqueous solution to exhibit bright fluorescence in response to sequential treatment of alkaline phosphatase (ALP) and ChT-L. Transmission electron microscopy, enzymatic kinetics, and in vitro fluorescence experiments validated that TPE-1p was efficiently dephosphorylated by ALP to generate TPE-1, which was recognized by ChT-L in the proteasome, and transformed to form nanofibers with strong fluorescence signals. Cell imaging experiments revealed that bright blue fluorescence was observed in TPE-1p-treated HeLa cells, whereas NIH3T3 and HepG2 cells showed less fluorescence at the same condition. The enhanced fluorescence signals in HeLa cells were attributed to the high activities of endogenous ALP and ChT-L. Moreover, TPE-1p was utilized to noninvasively assess the inhibition efficiency of a ChT-L inhibitor (bortezomib, abbreviated as Btz) in HeLa cells. Significant correlation was found between the fluorescence signals of TPE and the viabilities of Btz-treated cells in concentration ranges from 0 to 1 µM, indicating that TPE-1p could be employed to predict the activity of ChT-L inhibitors. The design of the cascade-activated AIEgen-peptide probe provides a viable approach for noninvasively monitoring the ChT-L activity of proteasomes in living cells, which facilitates high-throughput screening of ChT-L inhibitors in cancer therapy.

Self-assembling NBD-tripeptide as a dual-mode colorimetric platform for naked eye and smartphone joint detection of micro to nanomolar Copper(II) ions.

Compared to conventionally synthesized organic compounds, peptides with amphiphiles have unique advantages, especially in self-assembly. Herein, we reported a peptide-based molecule rationally designed for the visual detection of copper ions (Cu2+) in multiple modes. The peptide exhibited excellent stability, high luminescence efficiency, and environmentally responsive molecular self-assembly in water. In the presence of Cu2+, the peptide undergoes an ionic coordination interaction and a coordination-driven self-assembly process that leads to the quenching of fluorescence and the formation of aggregates. Therefore, the concentration of Cu2+ can be determined by the residual fluorescence intensity and the color difference between peptide and competing chromogenic agents before and after Cu2+ incorporation. More importantly, this variation in fluorescence and color can be presented visually, thus allowing qualitative and quantitative analysis of Cu2+ based on the naked eye and smartphones. Overall, our study not only extends the application of self-assembling peptides but also provides a universal method for dual-mode visual detection of Cu2+, which would significantly promote point-of-care testing (POCT) of metal ions in pharmaceuticals, food, and drinking water.

Protocol to image deuterated propofol in living rat neurons using multimodal stimulated Raman scattering microscopy.

Propofol is a widely used anesthetic important in clinics, but like many other bioactive molecules, it is too small to be tagged and visualized by fluorescent dyes. Here, we present a protocol to visualize deuterated propofol in living rat neurons using stimulated Raman scattering (SRS) microscopy with carbon-deuterium bonds serving as a Raman tag. We describe the preparation and culture of rat neurons, followed by optimization of the SRS system. We then detail neuron loading and real-time imaging of anesthesia dynamics. For complete details on the use and execution of this protocol, please refer to Oda et al.1.

Genome-wide analysis of transcriptome and histone modifications in Brassica napus hybrid.

Although utilization of heterosis has largely improved the yield of many crops worldwide, the underlying molecular mechanism of heterosis, particularly for allopolyploids, remains unclear. Here, we compared epigenome and transcriptome data of an elite hybrid and its parental lines in three assessed tissues (seedling, flower bud, and silique) to explore their contribution to heterosis in allopolyploid B. napus. Transcriptome analysis illustrated that a small proportion of non-additive genes in the hybrid compared with its parents, as well as parental expression level dominance, might have a significant effect on heterosis. We identified histone modification (H3K4me3 and H3K27me3) variation between the parents and hybrid, most of which resulted from the differences between parents. H3K4me3 variations were positively correlated with gene expression differences among the hybrid and its parents. Furthermore, H3K4me3 and H3K27me3 were rather stable in hybridization and were mainly inherited additively in the B. napus hybrid. Together, our data revealed that transcriptome reprogramming and histone modification remodeling in the hybrid could serve as valuable resources for better understanding heterosis in allopolyploid crops.

Nanofibrillar peptide hydrogels for self-delivery of lonidamine and synergistic photodynamic therapy.

The use of lonidamine (LND) in photodynamic therapy (PDT) provides a viable approach to develop low-dose PDT modules with high efficacy, for LND potentiates cytotoxicity of photosensitizers through dysregulation of mitochondrial function. Yet, the efficacy of LND is restricted by its low accumulation in cancer cells, especially in the mitochondrial compartments. To address the problem, we design an LND-derived self-assembling peptide molecule (LND-K) that dually targets integrin receptors and mitochondria of cancer cells. The targeted cellular delivery of LND-K gives higher efficacy in ablation of mitochondrial function in melanoma cells A375, as compared to free LND or the control molecule that lacks mitochondria-targeting moieties. To integrate LND-K in a typical PDT module, we develop a nanofibrillar hydrogel system through co-assembly of LND-K and TPPS4, an anionic photosensitizer that forms tight electrostatic interactions with cationic residues of LND-K. Notably, hydrogel formulation of LND-K/TPPS4 facilitates slow release of TPPS4 over 14 days in vitro, and displays a longer retention time than aqueous solution of TPPS4in vivo. By integrating a mitochondria-targeted molecule (LND-K) in a typical PDT module, we achieve synergistic killing of A375 cells with dual drugs, where LND-K not only serves as a chemotherapeutic drug, but also potentiates the cytotoxicities of TPPS4 toward A375 cells in vitro and in vivo. The peptide-based drug self-delivery system promises the development of efficacious combination treatments against cancer, that integrate cell sensitization with existing anticancer modules (e.g., chemotherapy and PDT) for enhanced therapeutic efficacy. STATEMENT OF SIGNIFICANCE: This study reports the design and synthesis of a lonidamine (LND)-derived self-assembling peptide (LND-K) that dually targets integrin receptors and mitochondria of cancer cells. Under the precision guidance of a mitochondria-targeting sequence, LND-K-containing nanofibers target mitochondria and ablate mitochondrial functions. On one hand, the targeted delivery of LND-K reduces cell viabilities through a chemotherapy route; on the other hand, LND-K sensitizes cancer cells for subsequent PDT treatment with enhanced efficacy, which is mediated by induction of ROS, loss of mitochondrial membrane potential, and decrease of cellular ATP level. We believe that the design of mitochondria-targeted drug delivery systems with a self-assembling molecule provides a new approach to potentiate cytotoxicity of photosensitizers in a low-dose PDT module.

CEBPB is associated with active tumor immune environment and favorable prognosis of metastatic skin cutaneous melanoma.

Metastatic skin cutaneous melanoma (SKCM) is a common malignancy that accounts for low morbidity but high mortality of skin cancer. SKCM is characterized by high lymphocytic infiltration, whereas the states of infiltrated cells are variable in patients leading to a heterogeneous prognosis and hindering appropriate clinical decisions. It is therefore urgent to identify markers associated with lymphocytic infiltration, cellular conditions, and the prognosis of SKCM. In this study, we report that CEBPB, a transcriptional factor, is mainly expressed in macrophages in metastatic SKCM and associated with an active tumor immune environment and a favorable prognosis through integrated analysis of single-cell and bulk RNA-seq datasets. High CEBPB expression is significantly associated with active inflammation and immune response pathways in both macrophages and bulk SKCM tumor tissues. A signature based on CEBPB-associated genes that are specifically expressed in macrophages could robustly and prognostically separate different metastatic SKCM patients. In addition, the associations between the metastatic SKCM tumor signature and microenvironment with respect to T-cell recruitment and state, inflammation response, angiogenesis, and so on were also determined. In conclusion, we present here the first report on CEBPB in tumor immune environment and prognosis regulation in metastatic SKCM and construct a reliable signature, which should provide a useful biomarker for stratification of the patient's prognosis and therapeutic selection.

Monolayer NaW2O2Br6: a gate tunable near-infrared hyperbolic plasmonic surface.

Electrically tunable hyperbolic polaritons in two dimensional (2D) materials can offer unexplored opportunities in integrating photonics and nano-optoelectronics into a single chip. Here, we suggest that monolayer NaW2O2Br6 can host electrically tunable hyperbolic plasmon polaritons for infrared light via first-principles calculations. 2D monolayer NaW2O2Br6 exhibits an extremely anisotropic metallic property: conducting for one direction but almost insulating for the other direction, which could be considered as a 2D analogue of metal/dielectric multilayers, a typical structure for hyperbolic metamaterials. More interestingly, we also demonstrate that the hyperbolic properties in the near-infrared range, including the hyperbolic windows, figure of merit, and propagation directions of plasmon beams, can be effectively modulated by carrier doping at the order of 1013 cm-2, which even can be accessed by solid-gated field effect transistors. Thus, it is anticipated that monolayer NaW2O2Br6 has a great potential in constructing field programmable polariton nanodevices for emerging and diverse photonic applications.

Injectable and Self-Healing Hydrogel Based on Chitosan-Tannic Acid and Oxidized Hyaluronic Acid for Wound Healing.

Self-healing performance plays an important role in the in situ microinvasive injection of hydrogels, which can reduce sudden drug release and prolong the service life of hydrogels. In this paper, a multifunctional injectable and self-healing hydrogel for wound healing was developed. Chitosan (CS) was modified with TA to achieve potential adhesion, anti-inflammatory properties, and slower degradation rate. The hydrogel was formed by Schiff base reaction based on amino groups in CS and aldehyde groups in oxidized hyaluronic acid (OHA). The gel formation process was quick and convenient in mild conditions without extra initiators. Due to the dynamically reversible covalent bonds, the hydrogel could self-heal within 2 min after injection. It also had good biocompatibility and hemostatic performance. With the addition of TA, the hydrogel acquired anti-inflammatory properties and promoted cell growth, effectively accelerating the wound-healing process in vivo. The CS-TA/OHA hydrogel is expected to be used for skin repair.

Enzymatic Synthesis of Peptide Nanofibers for Self-Delivery of Indomethacin and Tyroservatide in Cancer Therapy.

Non-steroidal anti-inflammatory drugs (NSAIDs) have drawn considerable attention in the field of cancer treatment, yet these drugs display limited potency and selectivity against cancer cells. To address these problems, we designed a peptide-based self-delivery system [Indomethacin-Phe-Phe-Tyr (H2PO3)-Ser-Val, IDM-FFpYSV] that combines an NSAID molecule (indomethacin, or IDM) and a segment of anticancer tripeptide (tyroservatide, or YSV). IDM-FFpYSV is capable of self-assembling in an aqueous solution to afford nanofibrillar hydrogels under the catalysis of alkaline phosphatases (ALPs), which are overexpressed on the plasma membrane of cancer cells. The IDM-FFpYSV + ALP hydrogel displays a continuous release profile of peptide drugs, whereas a solution mixture of pure drugs (IDM-OH + pYSV + ALP) shows burst release of drug moieties. The treatment of IDM-FFpYSV selectively inhibits the proliferation of HeLa cells in vitro, with precise regulations of intracellular targeting proteins (COX-2 and AC-H3). The enhanced potency and selectivity of IDM-FFpYSV are found to be attributed to enhanced cellular uptake of peptide drugs, which involves a caveolae-mediated endocytosis pathway. Furthermore, intravenous administration of the IDM-FFpYSV formulation significantly inhibits the tumor growth in a HeLa-xenografted mouse model, whereas treatment of solution mixtures of pure drugs (IDM-OH + pYSV) fails to do so. Taken together, the study provides a viable strategy to augment anticancer efficacies of self-delivery system through molecular integration of multiple anticancer elements with an enzyme-instructed self-assembly process.