Lentinan-based pH-responsive nanoparticles achieve the combination therapy of tumors.

Cancer poses a significant threat to human health, and there is an urgent need for more effective treatments. Combining chemotherapy and immunotherapy is an effective strategy to enhance curative outcomes and holds great potential for widespread application. The natural phytochemical genistein (GEN) exhibits cytotoxicity against tumors and is a potential chemotherapeutic agent. Lentinan (LTN) is a natural polysaccharide with immune-enhancing properties that has been utilized in tumor treatment. This study constructed a pH-responsive nanoparticle GEN@LTN-BDBA with chemotherapy and immunotherapy functions using GEN and LTN. After characterizing the nanoparticles, the molecular mechanism of GEN@LTN-BDBA formation was explored using in-silico simulation. GEN@LTN-BDBA can significantly inhibit the proliferation of A549 and HepG2 cells in vitro. The in vivo experiment results demonstrated that treatment with GEN@LTN-BDBA can significantly reduce tumor cell mass and prevent metastasis. In this nanoparticle, GEN induced oxidative stress and apoptosis of tumor cells. Meanwhile, the released LTN initiated an anti-tumor immune response by promoting dendritic cell maturation and upregulating the expression of costimulatory molecules and major histocompatibility complex. The construction method of GEN@LTN-BDBA can be extended to the preparation of other polysaccharides and hydrophobic chemotherapy molecules, offering a novel strategy to enhance the low efficacy of monotherapy.

Novel self-assembled micelles of dual-modified dextrin with pH responsiveness via grafted octenyl succinic anhydride and cysteamine for curcumin delivery.

In this study, a novel dextrin-based micelle (OSAD-SH), dual-modified with octenyl succinic anhydride (OSA) and cysteamine, was developed to address the acid instability issues of micelle modified only by OSA and designed for curcumin delivery. Three amphiphilic OSAD-SH polymers with different free sulfhydryl content were first synthesized. The study demonstrated that OSAD-SH micelles exhibited strong self-assembly properties, appearing as spheres with diameters ranging from 92.41 to 194.20 nm. Blank micelles showed good dilution resistance, as well as stability against acid, thermal, and ionic strength. The curcumin encapsulated by the micelles was in an amorphous state. In vitro release experiment demonstrated that curcumin released from OSAD-SH micelles exhibited pH responsiveness. The Ritger-Peppas model effectively predicted the release behavior of curcumin, which followed a super case-II transport. The OSAD-SH micelle will be a promising nanocarrier for improving the physicochemical properties of curcumin in food fields.

Harnessing chemical functionality of xylan hemicellulose towards carbohydrate polymer-based pH/magnetic dual-responsive nanocomposite hydrogel for drug delivery.

This study reports a pH/magnetic dual-responsive hemicellulose-based nanocomposite hydrogel with nearly 100 % carbohydrate polymer-based and biodegradable polymer compositions for drug delivery. We synthesized pure Fe3O4 magnetic nanoparticles (Fe3O4 MNPs) using a co-precipitation method, then engineering xylan hemicellulose (XH), acrylic acid, poly(ethylene glycol) diacrylate, and Fe3O4 to synthesize the pH/magnetic dual-responsive hydrogel (Fe3O4@XH-Gel), through graft polymerization on XH with in-situ doping Fe3O4 MNPs initiated by the ammonium persulfate/tetramethylethylenediamine redox system. Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (1H NMR), X-ray diffractometry (XRD), scanning electron microscopy and energy dispersive spectrometer (SEM-EDS), high-resolution transmission electron microscopy (HRTEM), Brunauer-Emmett-Teller (BET), swelling gravimetric analysis, vibrating sample magnetometer (VSM) were employed to analyze the hydrogel's chemical structures, morphologies, pH-responsive behaviors, and magnetic responsiveness characteristics, mechanical and rheological properties, as well as cytotoxicity and biodegradability. The results indicate that the Fe3O4@XH-Gel exhibited excellent dual responsiveness to pH and magnetism. Furthermore, an emphasis was placed on the in-depth analysis of the pH response mechanism. Finally, we utilized this cutting-edge hydrogel to investigate the controlled-release behavior of two model drugs, Acetylsalicylic acid and Theophylline. The hydrogel demonstrated exceptional controlled release attributes, positioning it as a potential carrier for targeted drug delivery, particularly to the gastrointestinal conditions.

Synthesis of Dual-Responsive Amphiphilic Glycomacromolecules: Controlled Release of Glycan Ligands via pH and UV Stimuli.

This work presents a versatile strategy for the synthesis of dual stimuli-responsive amphiphilic glycomacromolecules with tailored release properties. Amphiphilic precision glycomacromolecules (APGs) derived from tailor-made building blocks using solid phase polymer synthesis form glycofunctionalized micelles, a versatile class of materials with applications in drug delivery, as antiinfection agents as well as simple cell mimetics. In this work, this concept is extended by integrating cleavable building blocks into APGs now allowing stimuli-responsive release of glycan ligands or destruction of the micelles. This study incorporates a newly designed acid-labile building block, 4-(4-(((((9H-fluoren-9-yl)methoxy)carbonyl)amino)methyl)-1,3-dioxolan-2-yl)benzoic acid (DBA), suitable also for other types of solid phase or amide chemistry, and an established UV-cleavable 2-nitrobenzyl linker (PL). The results demonstrate that both linkers can be cleaved independently and thus allow dual stimuli-responsive release from the APG micelles. By choosing the APG design e.g., placing the cleavable linkers between glycomacromolecular blocks presenting different types of carbohydrates, they can tune APG and micellar stability as well as the interaction and cluster formation with a carbohydrate-recognizing lectin. Such dual-responsive glycofunctionalized micelles have wide potential for use in drug delivery applications or for the development as anti-adhesion agents in antiviral and antibacterial treatments.

Responsive Acrylamide-Based Hydrogels: Advances in Interpenetrating Polymer Structures.

Hydrogels, composed of hydrophilic homopolymer or copolymer networks, have structures similar to natural living tissues, making them ideal for applications in drug delivery, tissue engineering, and biosensors. Since Wichterle and Lim first synthesized hydrogels in 1960, extensive research has led to various types with unique features. Responsive hydrogels, which undergo reversible structural changes when exposed to stimuli like temperature, pH, or specific molecules, are particularly promising. Temperature-sensitive hydrogels, which mimic biological processes, are the most studied, with poly(N-isopropylacrylamide) (PNIPAm) being prominent due to its lower critical solution temperature of around 32 °C. Additionally, pH-responsive hydrogels, composed of polyelectrolytes, change their structure in response to pH variations. Despite their potential, conventional hydrogels often lack mechanical strength. The double-network (DN) hydrogel approach, introduced by Gong in 2003, significantly enhanced mechanical properties, leading to innovations like shape-deformable DN hydrogels, organic/inorganic composites, and flexible display devices. These advancements highlight the potential of hydrogels in diverse fields requiring precise and adaptable material performance. In this review, we focus on advancements in the field of responsive acrylamide-based hydrogels with IPN structures, emphasizing the recent research on DN hydrogels.

Fabrication of Fully Positively Charged Layer-by-Layer Polyelectrolyte Nanofilms with pH-Dependent Swelling Properties.

Nanofilms fabricated by layer-by-layer (LbL) assembly from polyelectrolytes (PEs) are important materials for various applications. However, PE films cannot retain the charges along the polymer chains during fabrication, resulting in a low charge density. In this study, the preparation of LbL nanofilms with preserved positive charges via a controllable and efficient approach was achieved. To fabricate fully positively charged (FPC) LbL nanofilms, a polycation, poly-l-lysine, was partially grafted with azide and alkyne groups. Through copper-catalyzed azide-alkyne cycloaddition and the LbL procedure, nanofilms were fabricated with all of the individual layers covalently bonded, improving the pH stability of the nanofilms. Because the resulting nanofilms had a high charge density with positive charges both inside and on the surface, they showed unique pH-dependent swelling properties and adsorption of negatively charged molecules compared with those of traditional polyelectrolyte LbL nanofilms. This kind of FPC nanofilm has great potential for use in sensors, diagnostics, and filter nanomaterials in the biomedical and environmental fields.

Development of pH-responsive porphyran-coated gold nanorods for tumor photothermal and immunotherapy.

Cancer poses a significant threat to human health, and monotherapy frequently fails to achieve optimal therapeutic outcomes. Based on this premise, porphyran (PHP), a marine polysaccharide with immunomodulatory function, was used as a framework to coat gold nanorods and construct a novel nanomedicine (PHP-MPBA-GNRs) combining photothermal therapy and immunotherapy. In this design, PHP not only maintained the dispersion stability and photothermal stability of gold nanorods but also could be released under weakly acidic conditions to activate anti-tumor immunity. In vivo studies have shown that PHP-MPBA-GNRs can effectively inhibit tumor cell proliferation and reduce metastasis under near-infrared (NIR) light irradiation. Preliminary mechanistic investigations revealed that PHP-MPBA-GNRs could increase reactive oxygen species (ROS) and induce apoptosis in cancer cells. The PHP in PHP-MPBA-GNRs can also activate dendritic cells and up-regulate the expression of co-stimulatory molecules and antigen-presenting complexes. All biological experiments, including in vivo tests, demonstrated that PHP-MPBA-GNRs achieved a combination of photothermal therapy and immunotherapy for tumors.

pH-response of protein-polysaccharide multilayers adsorbed on a flat gold surface: A surface plasmon resonance study.

Polysaccharide-protein multilayers (PPMLs) consisting of bovine serum albumin (BSA) and chondroitin sulfate (CS) are assembled in acidic solution (pH 4.2) via layer-by-layer deposition method. The formation of PPMLs on gold surface and their responsiveness to pH change from 4.2 to 7 is investigated by Surface Plasmon Resonance Spectroscopy. The buildup of the multilayer at pH 4.2 exhibits non-linear growth while the formation of the first layers is strongly affected by the physicochemical properties of the gold surface. Neutral solution (pH 7) affects the interactions between the biopolymers and results in a partially disassemble (disintegration) of the multilayer film. On one hand, the single pair of layers, BSA-CS and the double pair of layers, (BSA-CS)2, assemblies are stable in neutral pH, a result that will be of interest for biomedical applications. On the other hand, multilayer films consisting of more than four layers that is (BSA-CS)2

Multiple Chirality Switching of a Dye-Grafted Helical Polymer Film Driven by Acid & Base.

A stimuli-responsive multiple chirality switching material, which can regulate opposed chiral absorption characteristics, has great application value in the fields of optical modulation, information storage and encryption, etc. However, due to the rareness of effective functional systems and the complexity of material structures, developing this type of material remains an insurmountable challenge. Herein, a smart polymer film with multiple chirality inversion properties was fabricated efficiently based on a newly-designed acid & base-sensitive dye-grafted helical polymer. Benefited from the cooperative effects of various weak interactions (hydrogen bonds, electrostatic interaction, etc.) under the aggregated state, this polymer film exhibited a promising acid & base-driven multiple chirality inversion property containing record switchable chiral states (up to five while the solution showed three-state switching) and good reversibility. The creative exploration of such a multiple chirality switching material can not only promote the application progress of current chiroptical regulation technology, but also provide a significant guidance for the design and synthesis of future smart chiroptical switching materials and devices.

Copper peroxide loaded gelatin/oxide dextran hydrogel with temperature and pH responsiveness for antibacterial and wound healing activity.

Bacterial infection and tissue hypoxia always prevent wound healing, so multifunctional platforms with antimicrobial and oxygen-supplying functions were developed. However, they face many difficulties such as complex preparation and low oxygen release. To address this challenge, a copper peroxide loaded gelatin/oxide dextran hydrogel (CGO) was prepared. Surprisingly, CGO hydrogel as a wound dressing not only had good biocompatibility, injectivity, and mechanical properties, but also exhibited mild photothermal properties, temperature responsiveness, and pH responsiveness. After being applied to wounds infected with bacteria, CGO hydrogel released copper peroxide under near-infrared laser irradiation, which produced copper ions and hydrogen peroxide, combined with PTT to kill bacteria. After the bacteria were cleared from the wound and the pH of the wound was changed to be acidic, CGO hydrogel released copper peroxide via pH response. Copper ions and oxygen produced from copper peroxide accelerated wound healing by promoting angiogenesis. The multi-responsive and multi-mode treatment platform provided a potential strategy for treating bacteria-infected wounds.

Inflammatory microenvironment regulation and osteogenesis promotion by bone-targeting calcium and magnesium repletion nanoplatform for osteoporosis therapy.

Osteoporosis is the most common bone metabolic disease that affects the health of middle-aged and elderly people, which is hallmarked by imbalanced bone remodeling and a deteriorating immune microenvironment. Magnesium and calcium are pivotal matrix components that participate in the bone formation process, especially in the immune microenvironment regulation and bone remodeling stages. Nevertheless, how to potently deliver magnesium and calcium to bone tissue remains a challenge. Here, we have constructed a multifunctional nanoplatform composed of calcium-based upconversion nanoparticles and magnesium organic frameworks (CM-NH2-PAA-Ald, denoted as CMPA), which features bone-targeting and pH-responsive properties, effectively regulating the inflammatory microenvironment and promoting the coordination of osteogenic functions for treating osteoporosis. The nanoplatform can efficaciously target bone tissue and gradually degrade in response to the acidic microenvironment of osteoporosis to release magnesium and calcium ions. This study validates that CMPA possessing favorable biocompatibility can suppress inflammation and facilitate osteogenesis to treat osteoporosis. Importantly, high-throughput sequencing results demonstrate that the nanoplatform exerts a good inflammatory regulation effect through inhibition of the nuclear factor kappa-B signaling pathway, thereby normalizing the osteoporotic microenvironment. This collaborative therapeutic strategy that focuses on improving bone microenvironment and promoting osteogenesis provides new insight for the treatment of metabolic diseases such as osteoporosis.

Smart osteoclasts targeted nanomedicine based on amorphous CaCO3 for effective osteoporosis reversal.

BACKGROUND: Osteoporosis is characterized by an imbalance in bone homeostasis, resulting in the excessive dissolution of bone minerals due to the acidified microenvironment mediated by overactive osteoclasts. Oroxylin A (ORO), a natural flavonoid, has shown potential in reversing osteoporosis by inhibiting osteoclast-mediated bone resorption. The limited water solubility and lack of targeting specificity hinder the effective accumulation of Oroxylin A within the pathological environment of osteoporosis. RESULTS: Osteoclasts' microenvironment-responsive nanoparticles are prepared by incorporating Oroxylin A with amorphous calcium carbonate (ACC) and coated with glutamic acid hexapeptide-modified phospholipids, aiming at reinforcing the drug delivery efficiency as well as therapeutic effect. The obtained smart nanoparticles, coined as OAPLG, could instantly neutralize acid and release Oroxylin A in the extracellular microenvironment of osteoclasts. The combination of Oroxylin A and ACC synergistically inhibits osteoclast formation and activity, leading to a significant reversal of systemic bone loss in the ovariectomized mice model. CONCLUSION: The work highlights an intelligent nanoplatform based on ACC for spatiotemporally controlled release of lipophilic drugs, and illustrates prominent therapeutic promise against osteoporosis.

Influence of chitosan protonation degree in nanofibrillated cellulose/chitosan composite films and their morphological, mechanical, and surface properties.

Composite films of nanofibrillated cellulose (NFC) and chitosan (CS) were prepared by spray deposition method, and the influence of polymers ratio and protonation degree (α) of chitosan was evaluated. Films were characterized using morphological, mechanical, and surface techniques. Higher NFC content increased Young's modulus of film composites and reduced air permeability, while higher CS content increased water contact angle. Variations in the degree of protonation of chitosan from non-protonated (α = 0) to fully protonated (α = 1) in the NFC/CS composite film with a fixed composition allowed to modulate surface, mechanical, and structural properties, such as water contact angle (31.3-109.2°), Young's modulus (1.7-5.3 GPa), elongation at break (3.1-1.2 %), oxygen transmission rate (9.0-5.5 cm3/m2day) and air permeability (2074-426 s). Highly protonated chitosan composite films showed similar contact angles to pure chitosan films, while low protonated chitosan composite films presented contact angles similar to pure NFC films, suggesting a possible coating effect of NFC by CS through electrostatic interactions, evidenced by microscopy and spectroscopy analysis. By mixing both polymers and adjusting composition and protonation degree it was possible to enhance their properties, making pH adjustment a useful tool for NFC/CS composite films formation.

pH-sensitive release of nitric oxide gas using peptide-graphene co-assembled hybrid nanosheets.

Nitric oxide (NO) donating drugs such as organic nitrates have been used to treat cardiovascular diseases for more than a century. These donors primarily produce NO systemically. It is however sometimes desirable to control the amount, location, and time of NO delivery. We present the design of a novel pH-sensitive NO release system that is achieved by the synthesis of dipeptide diphenylalanine (FF) and graphene oxide (GO) co-assembled hybrid nanosheets (termed as FF@GO) through weak molecular interactions. These hybrid nanosheets were characterised by using X-ray diffraction, Raman spectroscopy, Fourier transform infrared spectroscopy, zeta potential measurements, X-ray photoelectron spectroscopy, scanning and transmission electron microscopies. The weak molecular interactions, which include electrostatic, hydrogen bonding and π-π stacking, are pH sensitive due to the presence of carboxylic acid and amine functionalities on GO and the dipeptide building blocks. Herein, we demonstrate that this formulation can be loaded with NO gas with the dipeptide acting as an arresting agent to inhibit NO burst release at neutral pH; however, at acidic pH it is capable of releasing NO at the rate of up to 0.6 µM per minute, comparable to the amount of NO produced by healthy endothelium. In conclusion, the innovative conjugation of dipeptide with graphene can store and release NO gas under physiologically relevant concentrations in a pH-responsive manner. pH responsive NO-releasing organic-inorganic nanohybrids may prove useful for the treatment of cardiovascular diseases and other pathologies.

Fine tuning of the net charge alternation of polyzwitterion surfaced lipid nanoparticles to enhance cellular uptake and membrane fusion potential.

Lipid nanoparticles (LNPs) coated with functional and biocompatible polymers have been widely used as carriers to deliver oligonucleotide and messenger RNA therapeutics to treat diseases. Poly(ethylene glycol) (PEG) is a representative material used for the surface coating, but the PEG surface-coated LNPs often have reduced cellular uptake efficiency and pharmacological activity. Here, we demonstrate the effect of pH-responsive ethylenediamine-based polycarboxybetaines with different molecular weights as an alternative structural component to PEG for the coating of LNPs. We found that appropriate tuning of the molecular weight around polycarboxybetaine-modified LNP, which incorporated small interfering RNA, could enhance the cellular uptake and membrane fusion potential in cancerous pH condition, thereby facilitating the gene silencing effect. This study demonstrates the importance of the design and molecular length of polymers on the LNP surface to provide effective drug delivery to cancer cells.

The study presents the unique characteristics of small interfering RNA (siRNA)-loaded lipid nanoparticles (LNPs) with different lengths of PGlu(DET-Car), revealing the length of PGlu(DET-Car) critically affects the formation of a stable LNP, the cellular uptake, membrane fusion, and gene silencing abilities.

All-polysaccharide, self-healing, pH-sensitive, in situ-forming hydrogel of carboxymethyl chitosan and aldehyde-functionalized hydroxyethyl cellulose.

In situ forming hydrogels are promising for biomedical applications, especially in drug delivery. The precursor solution can be injected at the target site, where it undergoes a sol-gel transition to afford a hydrogel. In this sense, the most significant characteristic of these hydrogels is fast gelation behavior after injection. This study describes an all-polysaccharide, rapidly in situ-forming hydrogel composed of carboxymethyl chitosan (CMCHT) and hydroxyethyl cellulose functionalized with aldehyde groups (HEC-Ald). The HEC-Ald was synthesized through acetal functionalization, followed by acid deprotection. This innovative approach avoids cleavage of pyran rings, as is inherent in the periodate oxidation approach, which is the most common method currently employed for adding aldehyde groups to polysaccharides. The resulting hydrogel exhibited fast stress relaxation, self-healing properties, and pH sensitivity, which allowed it to control the release of an encapsulated model drug in response to the medium pH. Based on the collected data, the HEC-Ald/CMCHT hydrogels show promise as pH-sensitive drug carriers.

An Antibiotic Nanobomb Constructed from pH-Responsive Chemical Bonds in Metal-Phenolic Network Nanoparticles for Biofilm Eradication and Corneal Ulcer Healing.

In the treatment of refractory corneal ulcers caused by Pseudomonas aeruginosa, antibacterial drugs delivery faces the drawbacks of low permeability and short ocular surface retention time. Hence, novel positively-charged modular nanoparticles (NPs) are developed to load tobramycin (TOB) through a one-step self-assembly method based on metal-phenolic network and Schiff base reaction using 3,4,5-trihydroxybenzaldehyde (THBA), ε-poly-ʟ-lysine (EPL), and Cu2+ as matrix components. In vitro antibacterial test demonstrates that THBA-Cu-TOB NPs exhibit efficient instantaneous sterilization owing to the rapid pH responsiveness to bacterial infections. Notably, only 2.6 µg mL-1 TOP is needed to eradicate P. aeruginosa biofilm in the nano-formed THBA-Cu-TOB owing to the greatly enhanced penetration, which is only 1.6% the concentration of free TOB (160 µg mL-1). In animal experiments, THBA-Cu-TOB NPs show significant advantages in ocular surface retention, corneal permeability, rapid sterilization, and inflammation elimination. Based on molecular biology analysis, the toll-like receptor 4 and nuclear factor kappa B signaling pathways are greatly downregulated as well as the reduction of inflammatory cytokines secretions. Such a simple and modular strategy in constructing nano-drug delivery platform offers a new idea for toxicity reduction, physiological barrier penetration, and intelligent drug delivery.

Coconut husk-lignin derived carbon dots incorporated carrageenan based functional film for intelligent food packaging.

Carbon dots (CDs) derived from sustainable natural feed-stocks like lignin have gained wide acceptance by virtue of their renewability and promising potential in intelligent sensing applications. The precursor lignin is isolated from agro-biomass waste, coconut husk through sodium hydroxide based extraction process. CDs are synthesised from amine functionalized lignin through solvothermal process and integrated into carrageenan biopolymer matrix (1, 2 and 3 wt%). The composite film with 2 wt% CDs (CARR2CD) showed optimum fluorescent emission intensity, excellent pH dependent fluorescent color change in the food pH range, reasonable tensile strength (46.50 ± 1.32 MPa) and 27 % increase in elongation at break. CDs imparted UV-light blocking properties (70 % UV-light) and enhanced hydrophobicity of the carrageenan matrix. CARR2CD film showed 84 % visible light transparency, 79 % reduction in oxygen transmittance rate (OTR), 81 % reduction in CO2 gas permeability and excellent antioxidant and antibacterial properties (against E. coli and S. aureus). As a practical application, the developed responsive packaging material is used to track pH change associated with milk spoilage via noticeable color change in fluorescent emission of the composite film. Thus, the developed responsive composite film paves a way for use as green and sustainable transparent intelligent food packaging material.

Strategic Structural Control of Polyserotonin Nanoparticles and Their Application as pH-Responsive Nanomotors.

Serotonin-based nanomaterials have been positioned as promising contenders for constructing multifunctional biomedical nanoplatforms due to notable biocompatibility, advantageous charge properties, and chemical adaptability. The elaborately designed structure and morphology are significant for their applications as functional carriers. In this study, we fabricated anisotropic bowl-like mesoporous polyserotonin (PST) nanoparticles with a diameter of approximately 170 nm through nano-emulsion polymerization, employing P123/F127 as a dual-soft template and 1,3,5-trimethylbenzene (TMB) as both pore expander and emulsion template. Their formation can be attributed to the synchronized assembly of P123/F127/TMB, along with the concurrent manifestation of anisotropic nucleation and growth on the TMB emulsion droplet surface. Meanwhile, the morphology of PST nanoparticles can be regulated from sphere- to bowl-like, with a particle size distribution ranging from 432 nm to 100 nm, experiencing a transformation from a dendritic, cylindrical open mesoporous structure to an approximately non-porous structure by altering the reaction parameters. The well-defined mesopores, intrinsic asymmetry, and pH-dependent charge reversal characteristics enable the as-prepared mesoporous bowl-like PST nanoparticles' potential for constructing responsive biomedical nanomotors through incorporating some catalytic functional materials, 3.5 nm CeO2 nanoenzymes, as a demonstration. The constructed nanomotors demonstrate remarkable autonomous movement capabilities under physiological H2O2 concentrations, even at an extremely low concentration of 0.05 mM, showcasing the 51.58 body length/s velocity. Furthermore, they can also respond to physiological pH values ranging from 4.4 to 7.4, exhibiting reduced mobility with increasing pH. This charge reversal-based responsive nanomotor design utilizing PST nanoparticles holds great promise for advancing the application of nanomotors within complex biological systems.

Overcoming Endosomal Escape Barriers in Gene Drug Delivery Using De Novo Designed pH-Responsive Peptides.

A major challenge in using nanocarriers for intracellular drug delivery is their restricted capacity to escape from endosomes into the cytosol. Here, we significantly enhance the drug delivery efficiency by accurately predicting and regulating the transition pH (pH0) of peptides to modulate their endosomal escape capability. Moreover, by inverting the chirality of the peptide carriers, we could further enhance their ability to deliver nucleic acid drugs as well as antitumor drugs. The resulting peptide carriers exhibit versatility in transfecting various cell types with a high efficiency of up to 90% by using siRNA, pDNA, and mRNA. In vivo antitumor experiments demonstrate a tumor growth inhibition of 83.4% using the peptide. This research offers a potent method for the rapid development of peptide vectors with exceptional transfection efficiencies for diverse pathophysiological indications.