Construction Of Drug Delivery Systems Research Articles

Enzyme-induced degradation of natural and artificial linear polyanions

Synthetic and natural polymers are widely used for constructing drug delivery systems. Biocompatibility, water solubility and non-toxicity make polymers a convenient matrix for encapsulation, delivery and release of bioactive compounds [1–6]. Coupling of a drug with a biodegraded polymer matrix is a promising way for a controlled drug delivery. Along this line, the degradation of the four polymers in the presence of two enzymes in aqueous solutions was investigated. The following polymers were used: natural polysaccharides, sodium alginate and sodium hyaluronate, artificial (modified) sodium carboxymethylcellulose and synthetic sodium polyacrylate (control); their degradation was caused by the addition of alginate lyase and hyaluronidase. The first enzyme only cleaved the specific alginate substrate and left three other intact. Contrastingly, the second enzyme degraded all three polysaccharides, including artificial carboxymethylcellulose, but did not degrade synthetic polyacrylate. The biodegradation of polymers was accompanied by decreasing the size of polymer particles in solution from 100-200 nm down to 20-30 nm; the latter are capable of removing from the body through the kidneys. The initial polysaccharides showed the negative surface charge in aqueous solution, which changed but retained negative after biodegradation. The initial and biodegraded polysaccharides demonstrated negligible cytotoxicity during long exposure period. The obtained results are valuable for the development of polymer carriers for drug encapsulation and delivery.

Research Progress of Disulfide Bond Based Tumor Microenvironment Targeted Drug Delivery System.

Cancer poses a significant threat to human life and health. Chemotherapy is currently one of the effective cancer treatments, but many chemotherapy drugs have cell toxicity, low solubility, poor stability, a narrow therapeutic window, and unfavorable pharmacokinetic properties. To solve the above problems, target drug delivery to tumor cells, and reduce the side effects of drugs, an anti-tumor drug delivery system based on tumor microenvironment has become a focus of research in recent years. The construction of a reduction-sensitive nanomedicine delivery system based on disulfide bonds has attracted much attention. Disulfide bonds have good reductive responsiveness and can effectively target the high glutathione (GSH) levels in the tumor environment, enabling precise drug delivery. To further enhance targeting and accelerate drug release, disulfide bonds are often combined with pH-responsive nanocarriers and highly expressed ligands in tumor cells to construct drug delivery systems. Disulfide bonds can connect drug molecules and polymer molecules in the drug delivery system, as well as between different drug molecules and carrier molecules. This article summarized the drug delivery systems (DDS) that researchers have constructed in recent years based on disulfide bond drug delivery systems targeting the tumor microenvironment, disulfide bond cleavage-triggering conditions, various drug loading strategies, and carrier design. In this review, we also discuss the controlled release mechanisms and effects of these DDS and further discuss the clinical applicability of delivery systems based on disulfide bonds and the challenges faced in clinical translation.

Nanoparticle-Based Drug Delivery Systems for Enhancing Bone Regeneration.

The treatment of bone defects has been a long-standing challenge in clinical practice. Among the various bone tissue engineering approaches, there has been substantial progress in the development of drug delivery systems based on functional drugs and appropriate carrier materials owing to technological advances in recent years. A large number of materials based on functional nanocarriers have been developed and applied to improve the complex osteogenic microenvironment, including for promoting osteogenic activity, inhibiting osteoclast activity, and exerting certain antibacterial effects. This Review discusses the physicochemical properties, drug loading mechanisms, advantages and disadvantages of nanoparticles (NPs) used for constructing drug delivery systems. In addition, we provide an overview of the osteogenic microenvironment regulation mechanism of drug delivery systems based on nanoparticle (NP) carriers and the construction strategies of drug delivery systems. Finally, the advantages and disadvantages of NP carriers are summarized along with their prospects and future research trends in bone tissue engineering. This Review thus provides advanced strategies for the design and application of drug delivery systems based on NPs in the treatment of bone defects.

Intelligent Delivery Systems in Tumor Metabolism Regulation: Exploring the Path Ahead.

Cancer metabolism plays multifaceted roles in the initiation and progression of tumors, and interventions in metabolism are considered fundamental approaches for cancer control. Within the vast metabolic networks of tumors, there exist numerous potential therapeutic targets, intricately interconnected with each other and with signaling networks related to immunity, metastasis, drug resistance, and more. Based on the characteristics of the tumor microenvironment, constructing drug delivery systems for multi-level modulation of the tumor microenvironment is proven as an effective strategy for achieving multidimensional control of cancer. Consequently, this article summarizes several features of tumor metabolism to provide insights into recent advancements in intelligent drug delivery systems for achieving multi-level regulation of the metabolic microenvironment in cancer, with the aim of offering a novel paradigm for cancer treatment.

Pyroptosis induction synergized with IDO inhibition of ternary biomedicine for photodynamic activated tumor immunotherapy

The development of immunotherapy is seriously limited by the insufficient tumor immunogenicity and immunosuppressive microenvironment. Pyroptosis is a new form of immunogenic cell death (ICD) associated with the gasdermin protein family, which has received increasing attention as a promising approach to activate antitumor immunity. Herein, we construct a ternary biomedicine (CNS) based on the self-assembly of photosensitizer chlorine e6 (Ce6), NLG919 (NLG) and simvastatin (Sim), which has a fairly high drug content, good stability and uniform morphology. Interestingly, the photodynamic therapy of CNS can generate reactive oxygen species (ROS) to induce intracellular oxidative stress, activating NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/Caspase-1 (Cas-1)/gasdermin D N-terminal domain (GSDMD-N) dependent pyroptosis. Further, Sim-mediated NLRP3 upregulation will also promote cell pyroptosis to activate ICD and stimulate immune responses. Benefiting from NLG-induced indoleamine 2,3-dioxygenase (IDO) inhibition, CNS is capable of improving the immunosuppressive microenvironment to enhance immunotherapy. Consequently, the pyroptosis induction synergized with IDO inhibition of CNS exhibits excellent antitumor immune activities, as evidenced by enhancing DCs maturation and effector memory T cells frequency, which significantly inhibit tumor growth and metastasis. This proposal of self-delivery ternary nanomedicine might open a new window to construct drug delivery systems for pyroptosis activated immunotherapy.

Development and Evaluation of an FDM Printed Nasal Device for CPZ Solid Nanoparticles.

Nasal drug delivery has been a focus of scientific interest for decades. A number of drug delivery systems and devices are available and have been highly successful in providing better and more comfortable therapy. The benefits of nasal drug delivery are not in question. The nasal surface provides an excellent context for the targeted delivery of active substances. In addition to the large nasal surface area and intensive absorption, the active substances delivered through the nose overcome the blood-brain barrier and can be delivered directly to the central nervous system. Formulations for nasal administration are typically solutions or liquid dispersed systems such as emulsions or suspensions. Formulation techniques for nanostructures have recently undergone intensive development. Solid-phase heterogeneous dispersed systems represent a new direction in pharmaceutical formulations. The wide range of possible examples and the variety of excipients allow for the delivery of a wide range of active ingredients. The aim of our experimental work was to develop a solid drug delivery system that possesses all of the above-mentioned advantageous properties. In developing solid nanosystems, we not only exploited the advantages of size but also the adhesive and penetration-enhancing properties of excipients. During formulation, several amphiphilic compounds with adhesion properties and penetration enhancing effects were incorporated. We used chlorpromazine (CPZ), which is mainly used in the treatment of psychotic disorders such as schizophrenia and bipolar disorder. Chlorpromazine has been previously investigated by our team in other projects. With the availability of previous methods, the analytical characterization of the drug was carried out effectively. Due to the frequent and severe side effects of the drug, the need for therapeutic dose reduction is indisputable. In this series of experiments, we succeeded in constructing drug delivery systems. Finely divided Na nanoparticles were formed using a Büchi B90 nanospray dryer. An important step in the development of the drug carrier was the selection of suitable inert carrier compounds. Particle size determination and particle size distribution analysis were performed to characterize the prepared nanostructures. As safety is the most important aspect of any drug formulation, all components and systems were tested with different biocompatibility assays. The tests performed demonstrated the safe applicability of our systems. The bioavailability of chlorpromazine was studied as a function of the ratio of the active ingredient administered nasally and intravenously. As described above, most nasal formulations are liquids, but our system is solid, so there is currently no tool available to accurately target this system. As a supplement of the project, a nasal dosing device was developed, corresponding to the anatomical structure; a prototype of the device was made using 3D FDM technology. Our results lay the foundation for the design and industrial scaling of a new approach to the design and production of a high-bioavailability nasal medicinal product.

Construction and Performance Evaluation of Nicandra physalodes (Linn.) Gaertn. Polysaccharide-Based Nanogel.

The nanogels made from these polysaccharides and their derivatives are often used to construct drug delivery systems owing to their biocompatible, biodegradable, non-toxic, water-soluble, and bioactive characteristics. In this work, a novel pectin with unique gelling properties was extracted from the seed of Nicandra physalodes (NPGP). The structural research indicated that NPGP was a low methoxyl pectin with a high content of galacturonic acid. NPGP-based nanogels (NGs) were accomplished employing the water in oil (W/O) nano-emulsion method. The cysteamine containing reduction-responsive bond and integrin-targeting RGD peptide were also grafted onto NPGP. The anti-tumor drug doxorubicin hydrochloride (DOX) was loaded during the formation of NGs, and the performance of DOX delivery was studied. The NGs were characterized by UV-vis, DLS, TEM, FT-IR, and XPS. The results showed that the prepared NGs were nanosized (167.6 ± 53.86 nm), had excellent encapsulation efficiency (91.61 ± 0.85%), and possessed a fine drug loading capacity (8.40 ± 0.16%). The drug release experiment showed that DOX@NPGP-SS-RGD had good redox-responsive performance. Furthermore, the results of cell experiments revealed good biocompatibility of prepared NGs, along with selective absorption by HCT-116 cells through integrin receptor-mediated endocytosis to play an anti-tumor effect. These studies indicated the potential application of NPGP-based NGs as targeted drug delivery systems.

Gallium Metal-Organic Nanoparticles with Albumin-Stabilized and Loaded Graphene for Enhanced Delivery to HCT116 Cells.

Gallium (III) metal-organic complexes have been shown to have the ability to inhibit tumor growth, but the poor water solubility of many of the complexes precludes further application. The use of materials with high biocompatibility as drug delivery carriers for metal-organic complexes to enhance the bioavailability of the drug is a feasible approach. Here, we modified the ligands of gallium 8-hydroxyquinolinate complex with good clinical anticancer activity by replacing the 8-hydroxyquinoline ligands with 5-bromo-8-hydroxyquinoline (HBrQ), and the resulting Ga(III) + HBrQ complex had poor water solubility. Two biocompatible materials, bovine serum albumin (BSA) and graphene oxide (GO), were used to synthesize the corresponding Ga(III) + HBrQ complex nanoparticles (NPs) BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs in different ways to enhance the drug delivery of the metal complex. Both of BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs can maintain stable existence in different solution states. In vitro cytotoxicity test showed that two nanomedicines had excellent anti-proliferation effect on HCT116 cells, which shown higher level of intracellular ROS and apoptosis ratio than that of cisplatin and oxaliplatin. In addition, the superior emissive properties of BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs allow their use for in vivo imaging showing highly effective therapy in HCT116 tumor-bearing mouse models. The use of biocompatible materials for the preparation of NPs against poorly biocompatible metal-organic complexes to construct drug delivery systems is a promising strategy that can further improve drug delivery and therapeutic efficacy.

A Universal Chemotactic Targeted Delivery Strategy for Inflammatory Diseases.

Above 50% of deaths can be attributed to chronic inflammatory diseases; thus, the construction of drug delivery systems based on effective interaction of inflammatory factors with chemotactic nanoparticles is meaningful. Herein, a zwitterion-based artificial chemotactic nanomotor is proposed for universal precise targeting strategy in vivo, where the high level of reactive oxygen species (ROS) and inducible nitric oxide synthase (iNOS) in inflammatory sites are used as a chemoattractant. Multidimensional static models, dynamic models, and in vivo models are established to evaluate chemotactic performance. The results show that the upregulated ROS and iNOS can induce the chemotaxis of nanomotors to diseased tissues in inflammation-related disease models. Further, mesoscale hydrodynamics simulations are performed to explain the chemotactic behavior of the nanomotors. Such a chemotactic delivery strategy is expected to improve delivery efficiency and may be applicable to a variety of inflammatory diseases.

A fluorescent, chirality-responsive, and water-soluble cage as a multifunctional molecular container for drug delivery.

In recent years, the rational design and construction of drug delivery systems (DDSs) via a supramolecular approach for improving chemical therapeutics have gained significant attention. Here, we report a host-guest DDS formed from a fluorescent, chirality-responsive, and water-soluble tetraphenylethene-based octacationic cage as a fluorescent/chiral probe, solubilizer, and molecular cargo, which can recognize chiral nucleoside drugs, enhance the solubility of insoluble drugs, and protect drugs from the outside environment by forming host-guest complexes in aqueous solution. Given the fluorescence properties and dynamically rotational conformation of tetraphenylethene (TPE) units, this fluorescent and chirality-responsive cage exhibits different responses including turn-on/turn-off fluorescence and negative/positive circular dichroism (CD) when binding with different chiral nucleoside drugs in water, resulting in multiple-responsive photophysical behaviors for these chiral drugs. Furthermore, this water-soluble cationic cage with a hydrophobic cavity can improve the water solubility of insoluble drugs (e.g., CPT) by forming host-guest complexes in water. More importantly, this multifunctional cage exhibits a low toxicity to both human colon and breast cancer cell lines in vitro, and drugs encapsulated by the cage are more effective in killing cancer cells than drugs alone. Finally, the on-off-on fluorescence responses in the formation and dissociation processes of the cage⊃drug complexes have been successfully used to monitor drug release and track drug delivery by fluorescence microscopy in vitro. Therefore, this fluorescent, chirality-responsive, and water-soluble cage as a multifunctional molecular container can be used to construct a smart drug delivery system with several functions of fluorescence and CD detection, water solubilization, real-time monitoring, and chemotherapy.

Ubiquitin-like 3 as a new protein-sorting factor for small extracellular vesicles.

Ubiquitin-like 3 (UBL3) is a well-conserved ubiquitin-like protein (UBL) in eukaryotes and regulates the ubiquitin cascade, but the significant roles of UBL3 in cellular processes remained unknown. Recently, UBL3 was elucidated to be a post-translational modification factor that promotes protein sorting to small extracellular vesicles (sEVs). Proteins sorted into sEVs have been studied as etiologies of sEV-related diseases. Also, there have been attempts to construct drug delivery systems (DDSs) by loading proteins into sEVs. In this review, we introduce the new concept that UBL3 has a critical role in the protein-sorting system and compare structure conservation between UBL3 and other UBLs from an evolutionary perspective. We conclude with future perspectives for the utility of UBL3 in sEV-related diseases and DDS.Key words: UBL3, small extracellular vesicles, protein sorting, ubiquitin-like protein, post-translational modification.

Effective drug delivery system based on hydrophobin and halloysite clay nanotubes for sustained release of doxorubicin

Halloysite clay nanotubes (HNTs), which are natural nano-clays with a hollow tubular structure, have been widely studied for drug delivery and sustained release while largely limited by the complexity of surface modification. Hydrophobins are small surface-active proteins produced by filamentous fungi that self-assemble into nanolayers at hydrophobic/hydrophilic interfaces. In this study, hydrophobins including HGFI-his and a mutant MGF6-his were used as unique biomaterials to modify HNTs to construct drug delivery systems. Water contact angle and HNT dispersion assays demonstrated that MGF6-his performed better surface activity and rendered HNT more lasting stability than HGFI-his. MGF6-his-coated HNTs loaded with the anticancer drug doxorubicin hydrochloride ([email protected]) were further prepared and characterized by dynamic light scattering, fluorescence microscopy and transmission electron microscopy. This composite was found to form nanoparticles in size of 375.62 ± 17.85 nm and possess better dispersion stability owing to the coating of the MGF6-his. Excellent sustained release was observed at pH 3.3 and 5.0 but not at pH 7.4 in in vitro release assay. Moreover, an in vitro cytotoxicity assay showed that this system exhibited good bioactivity, killing about 70% of HeLa cells at a concentration of 150 μg/mL. Herein, the hydrophobin MGF6-his was designed as a novel approach for HNT surface modification, facilitating the dispersion and prolonging drug release simultaneously. These findings suggested that coating with hydrophobins has potential as a novel approach to develop HNT-based drug delivery systems.

Prepartion And Bio Pharmaceutical Evaluation Of Chronopharmaceutical Drug Delivery System Of Metoprolol

The basic purpose of constructing drug delivery systems is to design when and where the drug will be released. The episode of many biological events is really important for such knowledge. Metoprolol pulsatile drug delivery system was developed for this purpose, which can release the drug when blood pressure needs to be modulated in the early morning. The Cup and core techniques were used to build this system, which included immediate release (IR), sustained-release (SR), and a polycaprolactone plug layer. The formulation of the ingredients was facilitated by various preformulation studies. The IR and SR tablets were bilayered, with polycaprolactone entirely coating the IR layer. The IR and SR tablet release profiles were optimised for the F5 batch, which was then used to construct a pulsatile drug delivery system. Clinical trials were conducted with the prepared tablet, which included the use of BaSO4 tagged tablets for X-ray examinations. All of the findings indicated the optimal drug release of metoprolol, which can be used for individuals who are more prone to blood pressure abnormalities in the morning.

Repurposing Erythrocytes as a "Photoactivatable Bomb": A General Strategy for Site-Specific Drug Release in Blood Vessels.

Tumor vasculature has long been considered as an extremely valuable therapeutic target for cancer therapy, but how to realize controlled and site-specific drug release in tumor blood vessels remains a huge challenge. Despite the widespread use of nanomaterials in constructing drug delivery systems, they are suboptimal in principle for meeting this demand due to their easy blood cell adsorption/internalization and short lifetime in the systemic circulation. Here, natural red blood cells (RBCs) are repurposed as a remote-controllable drug vehicle, which retains RBC's morphology and vessel-specific biodistribution pattern, by installing photoactivatable molecular triggers on the RBC membrane via covalent conjugation with a finely tuned modification density. The molecular triggers can burst the RBC vehicle under short and mild laser irradiation, leading to a complete and site-specific release of its payloads. This cell-based vehicle is generalized by loading different therapeutic agents including macromolecular thrombin, a blood clotting-inducing enzyme, and a small-molecule hypoxia-activatable chemodrug, tirapazamine. In vivo results demonstrate that the repurposed "anticancer RBCs" exhibit long-term stability in systemic circulation but, when tumors receive laser irradiation, precisely releases their cargoes in tumor vessels for thrombosis-induced starvation therapy and local deoxygenation-enhanced chemotherapy. This study proposes a general strategy for blood vessel-specific drug delivery.

Recent progress in the applications of amino–yne click chemistry

This mini-review summarizes the recent research studies on the application of the amino–yne click reaction in surface immobilization, construction of drug delivery systems, preparation of hydrogel materials and synthesis of functional polymers.

Study of the Blood Compatibility of Sulfated Organosolv Lignins Derived from Abies sibirica and Larix sibirica Wood Pulp.

The effects of sulfated organosolv lignins derived from fir (Abies sibirica) and larch (Larix sibirica) (SLf and SLl; 4-3-7.5% sulfur, median-weight molecular mass 2960-4888 Da), on human blood/plasma clotting, platelet aggregation, and erythrocyte hemolysis were studied in vitro. Antithrombin activities of the samples were below 2 U/mg. Specimens of SLf (sulfur content 6.5, 6.6, and 7.5%, molecular weights 3503, 3487, and 3580 Da, respectively) and SLl (4.3 and 6.3%, 2960 and 3497 Da) in a concentration of 0.01 mg/ml did not prolong the blood clotting time, did not provoke human platelet aggregation, did not destroy erythrocyte membranes, and could be used for construction of drug delivery systems. The SLf sample (6.5%, sulfur, 3503 Da) in concentrations from 0.09 to 1.82 mg/ml did not stimulate platelet aggregation, reduced ADP-induced platelet aggregation, and 2-fold prolonged the blood/plasma clotting time 2-fold in comparison with control and could be used for creation of biomaterial with clot-resistant surface.

Chiral Active β-Glucan Nanoparticles for Synergistic Delivery of Doxorubicin and Immune Potentiation.

Backgroundβ-glucans are chiral polysaccharides with well-defined immunological properties and supramolecular wrapping ability of its chiral feature. However, the exploitation of chiral properties of these nanoparticles in drug delivery systems was seldom conducted.Methodsβ-glucan molecules with different chain lengths were extracted from yeast Saccharomyces cerevisiae and thereafter modified. In a conformation transition process, these β-glucan molecules were then self-assembled with anti-cancer drug doxorubicin into nanoparticles to construct drug delivery systems. The chiral interactions between the drug and carriers were revealed by circular dichroism spectra, ultraviolet and visible spectrum, fourier transform infrared spectroscopy, dynamic light scattering and transmission electron microscope. The immune-potentiation properties of modified β-glucan nanoparticles were evaluated by analysis of the mRNA expression in RAW264.7 cell model. Further, the antitumor efficacy of the nanoparticles against the human breast cancer were studied in MCF-7 cell model by cellular uptake and cytotoxicity experiments.Resultsβ-glucan nanoparticles can activate macrophages to produce immune enhancing cytokines (IL-1β, IL-6, TNF-α, IFN-γ). A special chirality of the carriers in diameter of 50~160 nm can also associate with higher drug loading ability of 13.9% ~38.2% and pH-sensitive release with a change of pH from 7.4 to 5.0. Cellular uptake and cytotoxicity experiments also prove that the chiral-active β-glucan nanoparticles can be used in anti-cancer nanomedicine.ConclusionThis work demonstrates that β-glucans nanoparticles with special chiral feature which leading to strong immunopotentiation ability and high drug loading efficiency can be developed as a novel type of nanomedicine for anti-cancer treatment.

A Reactive Oxygen Species-Responsive Poly(amino acids) Nanoparticle Loading Doxorubicin for Glioblastoma Multiforme Treatment.

Amino acids are significant for human life and therefore considered as the crucial nutrients for human body with high biosafety. Due to their high biocompatibilities and various physicochemical properties, their polymers can be applied to construct drug delivery systems for various diseases' treatments. Among them, glioblastoma multiforme received special attention and numerous efforts regarding to nanotechnology were developed to treat such tumor. However, the biosafety of the delivering materials in those efforts arises as a critical issue in consideration of the weak patients. Therefore, a ROSresponsive nanoparticle (DOX@PLSPL) with poly(amino acids) encapsulating doxorubicin was developed for glioblastoma multiforme treatment. DOX@PLSPL was constructed by poly-lysine and poly-leucine with high biocompatibility. The high doxorubicin encapsulation efficiency and the controlled release manner of DOX@PLSPL ensured its high anti-tumor effect. Totally, this DOX@PLSPL can be used as a promising drug delivery system for glioblastoma multiforme treatments.

Drug Delivery Systems Based on Poly(2‐Oxazoline)s and Poly(2‐Oxazine)s

AbstractPoly(2‐oxazoline)s (PAOx) represent an established class of polymer materials with a wide range of applications. In contrast, the homologous poly(2‐oxazine)s (PAOzi) are only gaining increasing attention in the past years. Despite their high synthetic modularity and excellent biological properties, reports describing their use as a platform for construction of drug delivery systems are still relatively sparse. In this report, an overview of the recent progress in the field of drug delivery systems based on PAOx and PAOzi polymers is provided and a comparison is made with systems based on other polymer carriers, particularly poly(ethylene glycol) (PEG) and poly(N‐hydroxypropylmethacrylamide) (PHPMA). The emerging potential of PAOx and PAOzi is highlighted in the context of current polymer therapeutics research.

Dual-Therapeutics-Loaded Mesoporous Silica Nanoparticles Applied for Breast Tumor Therapy.

A material that possesses high loading efficiency (in terms of delivering small molecular drugs, nucleic acids, peptides, and proteins) has various medical applications, such as in tumor diagnosis and gene therapy or chemotherapy of tumors. Mesoporous silica nanoparticles are ideal nanocarriers for constructing drug delivery systems because of the unique mesoporous channels for encapsulation and the sustainable release of anticancer drugs. Herein, we demonstrate a doxorubicin (DOX)-peptides double-loaded and -response nanodrug (DMK nanoplatforms) as a multifunctional nanoplatform for chemotherapy of tumors. The nanoparticles are prepared by a surface modification strategy. The KLAK and DOX release in an acidic/reductive tumor microenvironment, which efficiently penetrate cell nuclei and generate the antitumor effect. Our study provides a new approach for developing a smart drug delivery nanosystem, particularly for peptides-guided pH-sensitive chemotherapy.