Search

The efficacy of chemotherapeutic drugs in tumor treatment is limited by their toxicity and side effects due to their inability to selectively accumulate in tumor tissue. In addition, chemotherapeutic agents are easily pumped out of tumor cells, resulting in their inadequate accumulation. To overcome these challenges, a drug delivery system utilizing the amphiphilic peptide Pep1 was designed. Pep1 can self-assemble into spherical nanoparticles (PL/Pep1) and encapsulate paclitaxel (PTX) and lapatinib (LAP). PL/Pep1 transformed into nanofibers in an acidic environment, resulting in longer drug retention and higher drug concentrations within tumor cells. Ultimately, PL/Pep1 inhibited tumor angiogenesis and enhanced tumor cell apoptosis. The use of shape-changing peptides as drug carriers to enhance cancer cell apoptosis is promising. [Display omitted] • The drug-loaded peptide PL/Pep1 self-assembled to form spherical nanoparticles. • PL/Pep1 underwent a morphological transformation to prolong the retention of the encapsulated drugs. • PL/Pep1 inhibited tumor angiogenesis and enhanced tumor cell apoptosis. [ABSTRACT FROM AUTHOR]

Chemotherapy is an important cancer treatment modality, but the clinical utility of chemotherapeutics is limited by their toxic side effects, inadequate distribution and insufficient intracellular concentrations. Nanodrug delivery systems (NDDSs) have shown significant advantages in cancer diagnosis and treatment. Variable NDDSs that respond to endogenous and exogenous triggers have attracted much research interest. Here, we summarized nanomaterials commonly used for tumor therapy, such as peptides, liposomes, and carbon nanotubes, as well as the responses of NDDSs to pH, enzymes, magnetic fields, light, and multiple stimuli. Specifically, well-designed NDDSs can change in size or morphology or rupture when induced by one or more stimuli. The varying responses of NDDSs to stimulation contribute to the molecular design and development of novel NDDSs, providing new ideas for improving drug penetration and accumulation, inhibiting tumor resistance and metastasis, and enhancing immunotherapy. [ABSTRACT FROM AUTHOR]

A novel GHH copolymer was synthesized using hyaluronic acid modified with glycyrrhetinic acid and L-histidine (His), and doxorubicin-loaded GHH nanoparticles (DOX/GHH) were prepared for liver-targeted drug delivery and pH-responsive drug release. In the present study, GHH nanoparticles were characterized, and their pH-responsive behaviors were evaluated at different pH levels. The antitumor effect of the DOX/GHH nanoparticles was investigated in vitro and in vivo. Results showed that the DOX/GHH nanoparticles were spherical, and the particle sizes ranged from 238.1 to 156.7 nm with an increase in the degree of substitution of His. The GHH nanoparticles were obviously internalized into human hepatoblastoma cells. In vitro cytotoxicity assay results showed that the DOX/GHH nanoparticles exhibited a dose-dependent antitumor effect. Compared with free DOX, the DOX/GHH nanoparticles displayed higher antitumor efficacy. These results indicate that GHH nanoparticles could be a promising nano-delivery carrier of hydrophobic drugs for liver-targeted therapy. [ABSTRACT FROM AUTHOR]

The gut microbiota plays a significant role in the pathogenesis and remission of inflammatory bowel disease. However, conventional antibiotic therapies may alter microbial ecology and lead to dysbiosis of the gut microbiome, which greatly limits therapeutic efficacy. To address this challenge, novel nanomicelles that couple inulin with levofloxacin via disulfide bonds for the treatment of salmonellosis were developed in this study. Owing to their H 2 S-responsiveness, the nanomicelles can target the inflamed colon and rapidly release levofloxacin to selectively fight against enteric pathogens. Moreover, the embedded inulin can serve as prebiotic fiber to increase the amount of Bifidobacteria and Lactobacilli in mice with salmonellosis, thus maintaining the intestinal mechanical barrier and regulating the balance of the intestinal flora. Therefore, multifunctional nanomicelles had a better curative effect than pure levofloxacin on ameliorating inflammation in vivo. The pathogen-targeted glycovesicle represents a promising drug delivery platform to maximize the efficacy of antibacterial drugs for the treatment of inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Glycosaminoglycan (GAG) lyases are important tools for investigating the structure of GAGs and preparing low-molecular-weight GAGs. The PL35 family, a recently established polysaccharide lyase family, should be further investigated. In this study, we discovered a new GAG lyase, CHa1, which belongs to the PL35 family. When expressed heterologously in Escherichia coli (BL21), CHa1 exhibited high expression levels and solubility. The optimal activity was observed in Tris-HCl buffer (pH 7.0) or sodium phosphate buffer (pH 8.0) at 30 °C. The specific activities towards HA, CSA, CSC, CSD, CSE, and HS were 3.81, 13.03, 36.47, 18.46, 6.46, and 0.50 U/mg protein, respectively. CHa1 digests substrate chains randomly that acting as an endolytic lyase and shows a significant preference for GlcA-containing structures, prefers larger oligosaccharides (≥UDP8) and can generate a series of oligosaccharides composed mainly of the A unit when digesting CSA. These oligosaccharides include ΔC-A, ΔC-A-A, ΔC-A-A-A, ΔC-A-A-A-A, and ΔC-A-A-A-A-A. The residues Tyr257 and His421 play crucial roles in the catalytic process, and Ser211, Asn212, Asn213, Trp214, Gln216, Lys360, Arg460 and Gln462 may participate in the binding process of CHa1. This study on CHa1 contributes to our understanding of the PL35 family and provides valuable tools for investigating the structure of GAGs. [ABSTRACT FROM AUTHOR]

Glycosaminoglycan (GAG) lyases are important tools for investigating the structure of GAGs and preparing low-molecular-weight GAGs. The PL35 family, a recently established polysaccharide lyase family, should be further investigated. In this study, we discovered a new GAG lyase, CHa1, which belongs to the PL35 family. When expressed heterologously in Escherichia coli (BL21), CHa1 exhibited high expression levels and solubility. The optimal activity was observed in Tris-HCl buffer (pH 7.0) or sodium phosphate buffer (pH 8.0) at 30 °C. The specific activities towards HA, CSA, CSC, CSD, CSE, and HS were 3.81, 13.03, 36.47, 18.46, 6.46, and 0.50 U/mg protein, respectively. CHa1 digests substrate chains randomly that acting as an endolytic lyase and shows a significant preference for GlcA-containing structures, prefers larger oligosaccharides (≥UDP8) and can generate a series of oligosaccharides composed mainly of the A unit when digesting CSA. These oligosaccharides include ΔC-A, ΔC-A-A, ΔC-A-A-A, ΔC-A-A-A-A, and ΔC-A-A-A-A-A. The residues Tyr257 and His421 play crucial roles in the catalytic process, and Ser211, Asn212, Asn213, Trp214, Gln216, Lys360, Arg460 and Gln462 may participate in the binding process of CHa1. This study on CHa1 contributes to our understanding of the PL35 family and provides valuable tools for investigating the structure of GAGs. [ABSTRACT FROM AUTHOR]

[Display omitted] • The deformable drug-loaded peptide nanocarriers DM/Pep1 targeted breast cancer cells. • DM/Pep1 underwent morphological transformation to prolong the retention time of the encapsulated drugs. • DM/Pep1 upregulated CD4, induced calreticulin exposure, downregulated PD-L1 and enhanced antitumor immune response. Insufficient drug accumulation at tumor sites is one of the key factors leading to treatment failure in breast cancer (BC), and developing a chemotherapeutic drug delivery system that can improve the immune microenvironment to expand the benefits of immunochemotherapy for BC remains a challenge. To increase the efficacy of BC treatment by extending drug retention at the tumor site, we developed a pH-responsive peptide modified with the PHSCN peptide sequence (Pep1) that self-assembles to form spherical DM/Pep1 nanoparticles after encapsulating doxorubicin (DOX) and metformin (MET). In the acidic tumor microenvironment, spherical nanocarriers transform into aggregates with a high aspect ratio, facilitating DOX and MET release for combined chemotherapy and immunomodulation. In cellular experiments, this construct provided prolonged drug retention in BC cells. In a subcutaneous tumor mouse model, the DM/Pep1 nanoparticles exhibited a superior tumor inhibition effect compared to that of free DOX/MET. The DM/Pep1 nanocomplex upregulated CD4, induced calreticulin (CRT) exposure, downregulated PD-L1, and enhanced the MET-mediated antitumor immune response. The use of this pH-responsive peptide nanocarrier system with morphological transformation offers a promising strategy for BC therapy. [ABSTRACT FROM AUTHOR]

• Supramolecular binding strategy was developed to prepare novel COFs. • β-CD inclusion was used as building block for the preparation of COFs. • Por-CD-COF could greatly reduce the use of photoactive ingredients. • The threading of CD could significantly enhance the photoactivity of COFs. • Por-CD-COF exerted cyclodextrin enhanced PTT and PDT. As an emerging artificial porous material, covalent organic frameworks (COFs) with customizable structure and function, have always been the focus of polymer science. Controllable fabrication of COFs with brand-new structure is the top priority for its development. Here, the 'supramolecular binding' strategy is developed as a simple but efficient method to prepare COFs with novel structures and functions. By this means, polymeric rotaxanes threaded COFs, denoted as Por-CD-COF, was facilely prepared via the combination of dynamic covalent imine-bond formation with supramolecular self-assembly, in which the polyrotaxane formed via inclusion of aromatic linker with bactericidal active β-cyclodextrin macrocycle (CD) was condensed with the photosensitive porphyrin via the combination of mechanical grinding and solvothermal synthesis. The formation of polyrotaxane could change the distance between layers, avoiding the quench of photoactivity caused by the severe aggregation of layered structure. Under the same molar amount of reaction monomers, the weight of the Por-CD-COF is approaching five times of the CD-free COF, which could greatly reduce the use of photoactive ingredients. Further experiments demonstrated the introduction of CDs could also significantly improve the biocompatibility. Impressively, this special porphyrin-involved CD-COF, displays excellent photo activity, which could act as an efficient broad spectrum antibacterial agents realizing the combinational action of cyclodextrin enhanced photothermal and photodynamic antimicrobial at an extremely low quality of the effective photosensitizer (Porphyrin). Meanwhile, even at the same dose of fungicide, the bactericidal effect of Por-CD-COF is far exceeding the CD-free therapeutic agent. This novel synthetic strategy allows the incorporation of mechanically interlocked CDs (MIMs) into the porous polymeric materials, providing an easy access to low-cost preparation of COFs for the specific applications. [ABSTRACT FROM AUTHOR]

[Display omitted] • The deformable drug-loaded peptide nanocarriers PS/Pep1 achieved high penetration. • PS/Pep1 underwent morphological transformation to prolong the retention time of the encapsulated drugs. • In vivo and ex vivo experiments demonstrated that PS/Pep1 inhibits angiogenesis. • PS/pep1 can effectively inhibit tumor metastasis in vivo. Chemotherapeutic drugs have low aggregation rates and short retention times in tumors, severely limiting their clinical application. Additionally, the development and spread of solid tumors is highly dependent on neovascularization. An RGD-modified acid-responsive peptide was designed to encapsulate the chemotherapeutic drug paclitaxel (PTX) and the antiangiogenic drug sorafenib (SF), enabling them to self-assemble into nanoparticles (NPs) in a physiological environment. In an acidic environment, the release of PTX and SF was achieved when the drug-loaded experimental peptide PS/Pep1 transformed from spherical NPs into aggregates containing nanofibers, which effectively prolonged the retention of the encapsulated drug and increased drug accumulation. Furthermore, in vivo experiments provided compelling evidence of the strong inhibitory effects of PS/Pep1 on tumor growth and metastasis, as well as its effective suppression of angiogenesis. This targeted NP system that undergoes a morphological shift in the tumor microenvironment holds promise for enhancing the efficacy of the combined administration of chemotherapeutic and antiangiogenic drugs to inhibit tumor growth and metastasis. [ABSTRACT FROM AUTHOR]

The exploration and development of high-performance, durable and economic bifunctional electrocatalysts towards the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER) is essential but challenging for the development of rechargeable Zn–air batteries (ZABs). Metal coordinated conjugated microporous polymers (CMPs) with an inherent rigid structure and customizable elemental composition are regarded as ideal precursors for the target preparation of porous carbon-based catalysts. Whereas it is hard to obtain bifunctional catalysts from monometallic CMPs. Here, we report a bimetallic conjugated microporous polymer (CMP) composed of boron dipyrromethene (bodipy) and Fe/Co-porphyrin (BP-CMP). Direct pyrolysis of the BP-CMP yields a defect-enriched B,N-codoped carbon composite, denoted as BP-800, with embedded Co3Fe7 and Fe/Co–N sites. The high specific surface area (890 m2 g−1) and hierarchical pore structure provide easily accessible active sites, significantly enhancing the oxygen catalytic activity. Meanwhile, the additional doping of B imparts a synergistic effect to the catalyst, which could not only realize the fine adjustment of the electronic properties, but also of the surface polarities of the carbon matrix. Therefore, compared with the B-free catalyst (P-800), BP-800 presents outstanding bifunctional catalytic activity for electrochemical oxygen reactions. For example, it presents superior catalytic performance with a super long-term running stability and fuel immunity, as well as a favored 4e-reduction pathway for the reduction of oxygen (ORR) in the whole pH range. Furthermore, compared with a commercial Pt/C catalyzed battery, the homemade ZABs using BP-800 as the cathode catalyst presented a higher open-circuit voltage (1.526 V), power density (185 mW cm−2), discharge specific capacity (776 mA h gZn−1 at 10 mA cm−2) and a longer cycle life (94 h at 10 mA cm−2), as well as excellent rate capacity. Moreover, owing to the effective protection of porous carbon in the alloy nanoparticles, the rechargeable ZAB with the BP-800 catalyst delivers excellent stability during long-term charging–discharging cycles, comparable to that of the commercial Pt/C and IrO2 benchmarks. This work paves an avenue for the synthesis of stable and efficient electrocatalysts to drive the development of breathing Zn–air batteries. [ABSTRACT FROM AUTHOR]

Herein, Fe-phthalocyanine-based conjugated microporous polymer (Fe-Phth-CMP) coated metal organic framework (ZIF-67) composites, namely Fe-Phth-CMP@ZIF-67, were facilely prepared via a rational and effective solid-phase synthesis method, in which, ZIF-67 worked as both precursors and templates. Upon carbonization, these special composites, with controllable morphology similar to ZIF-67 and adjustable Fe/Co molar ratio, can be further converted into N-doped porous carbons embedded with highly dispersed FeCo alloy and Fe/Co–N active sites. The optimal catalyst (denoted as P 2 Z 3 -900, prepared in a mass ratio of m POP : m ZIF = 2 : 3) features hierarchical pore structure which could significantly enhance the mass transfer efficiency and promotes the exposure of active sites, leading to high ORR and OER activity in alkaline conditions, simultaneously. For example, P 2 Z 3 -900 presents a half-wave potential (E 1/2) of 0.81 V (vs RHE) with a diffusion-limited current density of 5.56 mA cm−2, comparable to commercial Pt/C (0.83 V and 5.60 mA cm−2), but much better than other prepared control samples. The Eonset of OER at 10 mA cm−2 reaches 1.60 V with a small Tafel slope of 57 mV dec−1. More importantly, the current synthetic method offers a rational strategy to structure-, morphology-, and element composition-controlled porous carbons, thereby finely regulating the property for efficient catalysis. A core-shell-structured POP@MOF composite was developed via solid-phase synthesis method. Upon carbonization, these special composites, with controllable morphology similar to ZIF-67 and adjustable Fe/Co molar ratio, can be further converted into N-doped porous carbons embedded with highly dispersed FeCo alloy and Fe/Co–N active sites. The obtained catalyst present prominent electrocatalytic performance for both ORR and OER in alkaline conditions. Image 1 [ABSTRACT FROM AUTHOR]

Liposomes have been widely used as drug carriers in both biomedical research and for clinical applications, allowing the stabilisation of therapeutic compounds and overcoming obstacles to cellular and tissue uptake. However, liposomes still have low targeting efficiency, resulting in insufficient killing of tumour cells and unnecessary damage to normal cells. In this study, glycyrrhetinic acid (GA) and peanut agglutinin (PNA) were used as ligands to prepare dual-ligand-modified doxorubicin-loaded liposomes (DOX-GA/PNA-Lips) to enhance the targeting accuracy and efficacy of drug delivery against malignant liver cancer. PNA and GA modification enhanced the binding ability of liposomes to liver cancer cells, leading to excellent tissue and cell targeting of DOX-GA/PNA-Lips. DOX-GA/PNA-Lips showed an effective anti-tumour effect in vivo and in vitro, with its targeted delivery facilitating attenuation of the toxic side effects of DOX. These results demonstrated that dual-ligand-modified liposomes may provide an effective strategy for the treatment of hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Tumour metastasis is one of the major factors leading to poor prognosis as well as lower survival among cancer patients. A number of studies investigating the inhibition of tumour metastasis have been conducted. It is difficult to achieve satisfactory results with surgery alone for distant metastatic tumours, and chemotherapy can boost the healing rate and prognosis of patients. However, the poor therapeutic efficacy of chemotherapy drugs due to their low solubility, lack of tumour targeting, instability in vivo, high toxicity and multidrug resistance hinder their application. Immunotherapy is beneficial to the treatment of metastatic cancers, but it also has disadvantages such as adverse reactions and acquired resistance. Fortunately, delivery of chemotherapeutic drugs with nanocarriers can reduce systemic reactions caused by chemotherapeutic agents and inhibit metastasis. This review discusses the underlying mechanisms of metastasis, therapeutic approaches for antitumour metastasis, the advantages of nanodrug delivery systems and their application in reducing metastasis. [Display omitted] • Immunotherapy for the treatment of metastasis is described. • Multiple mechanisms and components are closely connected with the course of metastasis. • Antitumour and antimetastasis effects based on nanocarriers are presented. • Clinical applications of nanodrug delivery systems against metastasis are introduced. [ABSTRACT FROM AUTHOR]

• DOX/IpYR achieved high penetration and long-term retention simultaneously. • DOX/IpYR regulated the expression of immune factors and PD-L1. • DOX/IpYR suppressed tumour growth and metastases. Conventional intratumoural drug delivery systems often struggle to achieve both high permeability and long-term retention. Smaller nanoparticles (NPs) readily diffuse into deep tumour regions, but their rapid clearance results in lower accumulation at tumour sites. Furthermore, although immunostimulatory molecules have been introduced for the immunotherapy of tumours, it is crucial to develop drug nanovehicles with immunomodulatory functions. Here, a novel self-assembled amphiphilic peptide, IpYR, self-assembled into spherical NPs after drug loading, which were transformed into nanofibres (NFs) with a high aspect ratio under the induction of alkaline phosphatase (ALP). This drug-loading system effectively prolonged the residence time of the chemotherapeutic drug in tumour tissues and displayed enhanced aggregation at tumour sites in vivo. Furthermore, the transformable peptide NPs not only inhibited tumour growth but also suppressed tumour metastasis. Importantly, the peptide nanovehicles inhibited the proliferation of Treg cells, downregulated the expression of immunosuppressive factors and PD-L1, and simultaneously stimulated the expression of immunogenic factors, effectively alleviating the immunosuppressive microenvironment. In conclusion, this transformable peptide-based nanodelivery system is a concise and promising nanoplatform for maintaining potent drug enrichment and inhibiting immunosuppression in the tumour microenvironment. [ABSTRACT FROM AUTHOR]

As a simple but effective approach to engineer the simultaneous geometric structure and composition diversity into one nano-material, hybrids have geared great research attention, recently. Here, a N-decorated sheet-on-rod heterostructure with hierarchical porosity, as well as homogeneously dispersed Co 5.47 N, Co 0.7 Fe 0.3 , and Fe/Co-Nx species on the phase interface, was developed via pyrolysis of a CMP-on-MOF bimetal hybrid, to achieve the bifunctional oxygen electrocatalytic activity. Conjugated microporous polymers (CMPs) are an emerging class of multifunctional materials combining the features of conventional conjugated polymers and porous materials, simultaneously. CMP-on-MOF was prepared via the assembly of Co-phthalocyanine-CMP (Co-CMP) on the surface of Fe-MIL-88B (Fe-MOF) through a solid-phase synthesis method. The optimized catalyst (PM-900), namely the product of hybrid pyrolysis, is obtained by finely regulating the composition of hybrid (m CMP to m MOF of 1:1) and pyrolysis temperature (900 °C) on the hybrid, simultaneously. The abundant Co 5.47 N, Co 0.7 Fe 0.3 , and atomically dispersed Fe/Co-Nx species are highly catalytically active, and the hierarchical porous structure provides easily accessible pathway for active sites, and the sheet-on-rod structure ensures a high electrical conductivity which is conducive for the catalysis. As a result, the optimum electrocatalyst, denoted as PM-900, presents a superb bifunctional electrocatalytic activity for both the oxygen reduction (ORR) and oxygen evolution reaction (OER) under alkaline conditions. Additionally, a home-made Zn–air battery (ZAB) comprising PM-900 catalyst presents prominent charge-discharge property even outperforms the mixture of Pt/C (20 wt%) and IrO 2. The hybrid strategy paves a new avenue for the rational design and synthesis of advanced bifunctional catalysts with intricate and unprecedented porous superstructures for reversible energy storage and conversion applications. N-decorated sheet-on-rod heterostructure with hierarchical porosity, as well as homogeneously dispersed Co 5.47 N, Co 0.7 Fe 0.3 , and Fe/Co-Nx species on the phase interface, was developed via pyrolysis of a CMP-on-MOF bimetal hybrid, to achieve the bifunctional oxygen electrocatalytic activity. [Display omitted] • CMP-on-MOF hybrid was employed as precursor for the preparation of bifunctional O 2 catalyst. • CMP-on-MOF bimetal was synthesized in the solid phase synthesis method. • Pyrolysis on hybrid yield sheet-on-rod heterostructure with hierarchical porosity. • PM-900 shows uniformly dispersed Co 5.47 N, Co 0.7 Fe 0.3 and Fe/CoNx on phase interface. • Zn-air battery comprising PM-900 presents prominent charge-discharge property. [ABSTRACT FROM AUTHOR]

Liver cancer is one of the most common malignancies worldwide and poses a serious threat to human health. The most important treatment method, liver cancer chemotherapy, is limited due to its high toxicity and poor specificity. Targeted drug delivery systems have emerged as novel therapeutic strategies that deliver precise, substantial drug doses to target sites via targeting vectors and enhance the therapeutic efficacy. In the present study, glycyrrhetinic acid-modified hyaluronic acid (GA-HA) was used as a carrier for the model drug docetaxel (DTX) to prepare DTX-loaded GA-HA nanoparticles (DTX/GA-HA-NPs). The results indicated that the DTX/GA-HA-NPs exhibited high monodispersity (particle dispersity index, 0.209±0.116) and desirable particle size (208.73±5.0 nm) and zeta potential (-27.83±3.14 mV). The drug loading capacity and encapsulation efficiency of the NPs were 12.59±0.68 and 85.38±4.62%, respectively. Furthermore, it was determined that FITC-GA-HA was taken up by cells and distributed in the cytoplasm. DTX and DTX/GA-HA (just the DTX delivered by the nanoparticle) aggregated and altered the structure of cellular microtubules. Compared with DTX alone, DTX/GA-HA-NPs had a stronger inhibitory effect on HepG2 cell proliferation and promoted apoptosis of HepG2 cells. All experimental results indicated that DTX/GA-HA-NPs were successfully prepared and had liver-targeting and antitumor activities in vitro, which provided a foundation for future in vivo studies of the antitumor effects of DTX/GA-HA-NPs. [ABSTRACT FROM AUTHOR]

Nanocarriers have been widely employed to deliver chemotherapeutic drugs for cancer treatment. However, the insufficient accumulation of nanoparticles in tumors is an important reason for the poor efficacy of nanodrugs. In this study, a novel drug delivery system with a self-assembled amphiphilic peptide was designed to respond specifically to alkaline phosphatase (ALP), a protease overexpressed in cancer cells. The amphiphilic peptide self-assembled into spherical and fibrous nanostructures, and it easily assembled into spherical drug-loaded peptide nanoparticles after loading of a hydrophobic chemotherapeutic drug. The cytotoxicity of the drug carriers was enhanced against tumor cells over time. These spherical nanoparticles transformed into nanofibers under the induction of ALP, leading to efficient release of the encapsulated drug. This drug delivery strategy relying on responsiveness to an enzyme present in the tumor microenvironment can enhance local drug accumulation at the tumor site. The results of live animal imaging showed that the residence time of the morphologically transformable drug-loaded peptide nanoparticles at the tumor site was prolonged in vivo , confirming their potential use in antitumor therapy. These findings can contribute to a better understanding of the influence of drug carrier morphology on intracellular retention. [Display omitted] • Tumor microenvironment enzyme induced the geometrical shape switch of amphiphilic peptide VLKpY nanoparticles. • The obtained VLKpY nanoparticles were simple but smart with no modification. • The drug carriers displayed cytotoxic effects against tumor cells. • VLKpY nanoparticles enhanced the retention time in tumor cells. [ABSTRACT FROM AUTHOR]

[Display omitted] • The acidic tumor microenvironment induced a geometrical shape change by amphiphilic peptide LKR nanoparticles. • The obtained targeted LKR nanoparticles were simple but effective with no modification. • Anticancer drugs can be loaded and encapsulated into LKR nanoparticles with no covalent crosslinking. • LKR nanoparticles enhanced the drug accumulation in tumor cells compared with normal mammalian cells. • LKR was used in combination with encapsulated drugs for antitumor therapy in vivo. Spatial accuracy is crucial in drug delivery, especially to increase the efficacy and reduce the side effects of antitumor drugs. In this study, we developed a simple and broadly applicable strategy in which a target peptide ligand was introduced to construct a pH-responsive drug-loading system to achieve targeted delivery and drug release in lesions. In addition to reaching the tumor tissue through passive targeting modalities such as the enhanced permeability and retention (EPR) effect, active targeting nanoparticles used RGD motifs coupled to nanocarriers to specifically bind certain integrins, such as α ν β3, which is expressed on the surface of tumor cells, to achieve active tumor cell targeting. Self-assembling peptides have significant advantages in their structural design. The amphiphilic peptide LKR could form a spherical and self-assembled nanoparticle, which encapsulated the fat-soluble antitumor drug doxorubicin (Dox) in neutral medium. The Dox-encapsulating peptide nanoparticles swelled and burst, rapidly releasing Dox in an acidic microenvironment. Flow cytometry and fluorescence detection showed that the self-assembled LKR nanoparticles enhanced the drug accumulation in tumor cells compared with normal mammalian cells. The Dox-encapsulating peptide nanoparticles exhibited desirable antitumor effects in vivo. In summary, the acidic microenvironment of tumors was used to induce drug release from a targeted peptide drug-loading system to enhance cellular uptake and therapeutic effects in situ , providing a promising therapeutic approach for the treatment of major diseases such as hepatoma. [ABSTRACT FROM AUTHOR]

• We previously developed GA-HA nanoparticles as liver-targeting drug carriers. • Adenine inhibits hepatic carcinoma cell proliferation time- and dose-dependently. • GA-HA NPs enhanced Ade liver-targeting and cellular uptake in vitro and in vivo. • Ade/GA-HA NPs showed good anti-tumor effects against HCC with good biocompatibility. • Ade/GA-HA NPs may serve as a liver-targeting drug delivery system for clinical use. Hepatocellular carcinoma (HCC), a common malignancy in China and globally, is primarily treated through surgical resection and liver transplantation, with chemotherapy as a significant synergistic option. Adenine (Ade), a nucleobase, exhibits antitumor effects by blocking human hepatic carcinoma cells in S phase and inhibiting tumor cell proliferation. However, its use is limited owing to its low solubility, poor targeting ability, and nephrotoxicity. Therefore, liver-targeting drug delivery systems have attracted considerable attention for the treatment of HCC. In this study, we explored the liver-targeting efficacy and antitumor effect of adenine-loaded glycyrrhetinic acid-modified hyaluronic acid (Ade/GA-HA) nanoparticles in vitro and in vivo. The GA-HA nanoparticles possessed obvious targeting specificity toward liver cancer cells, which was mainly achieved by the specific binding of the GA ligand to the GA receptor that was highly expressed on the liver cell membrane. In vitro and in vivo results showed that Ade/GA-HA nanoparticles could inhibit liver cancer cell proliferation and migration, promote apoptosis, and significantly inhibit the growth of tumor tissues. Altogether, this study is the first to successfully demonstrate that the targeting activity and antitumor effect of Ade against HCC are enhanced by using GA-HA nanoparticles in vitro and in vivo. [ABSTRACT FROM AUTHOR]

• pH triggered a geometrical shape switch by I 6 K 5 nanoparticles. • The obtained I 6 K 5 nanoparticles were simple but smart with no modification. • Anticancer drugs can be loaded and encapsulated into I 6 K 5 nanoparticles. • Tumor cells took in more I 6 K 5 nanoparticles than mammalian cells. • This system gives new insights in the field of cancer therapeutic platforms. The geometry of nanoparticles plays an important role in their performance as drug carriers. However, the pH-triggered geometrical shape switching of a cationic peptide consisting of isoleucine and lysine is seldom reported. In this work, we designed a cationic peptide with acid reactivity that can be loaded with the poorly soluble antitumor drug (doxorubicin (DOX)) to enhance tumor cell uptake and drug delivery. In a weakly acidic environment, a large portion of random coil structures formed, which subsequently led to nanoparticle destruction and rapid DOX release. In vitro studies demonstrated that this cationic peptide exhibits low toxicity to normal cells. The amount of DOX-encapsulating peptide nanoparticles taken up by tumor cells was greater than that taken up by normal cells. Our results indicated that the use of a weakly acidic microenvironment to induce geometric shape switching in drug-loaded peptide nanoparticles should be a promising strategy for antitumor drug delivery. [ABSTRACT FROM AUTHOR]

The elaborate modulation of the transforming growth factor β (TGF-β) superfamily signaling network plays an essential role in tooth morphogenesis and differentiation. In our previous studies, we have demonstrated that TGF-β1 promotes enamel mineralization and maturation using TGF-β1 gene conditional knockout (TGF-β1-cKO) mice. However, the specific regulatory mechanisms of TGF-β1 during enamel development remain unclear. Furthermore, we have previously found that the expression of WD repeat-containing protein 72(WDR72)in mouse enamel epithelium is decreased significantly in the absence of TGF-β1. Therefore, the aim of the present study was to investigate how TGF-β1 affects amelogenesis by regulating the expression of Wdr72. Histological examination showed that the absence of TGF-β1 in ameloblastic epithelial cells resulted in a reduction in enamel mineralization and a delay in enamel matrix protein absorption. TGF-β1, Runt-related transcription factor 2(RUNX2) and WDR72 were revealed to be colocalized in ameloblasts by immunohistochemistry, and it was also found that the expression of Runx2 and Wdr72 was markedly different between TGF-β1-cKO mice and wild type(TGF-β1-WT)mice. In addition, the effect of exogenous TGF-β1 on Wdr72 was more significant when RUNX2 was present than when RUNX2 was absent. Furthermore, we found that there were binding sites for RUNX2 on the promoter of Wdr72 and that Wdr72 expression was regulated by RUNX2. Collectively, our results suggest that TGF-β1 affects enamel mineralization by modulating RUNX2 and thus affecting the expression of Wdr72. [ABSTRACT FROM AUTHOR]