Dual-responsive Drug Delivery Research Articles

Dual Responsive Magnetic Drug Delivery Nanomicelles with Tumor Targeting for Enhanced Cancer Chemo/Magnetothermal Synergistic Therapy.

Stimulus-responsive nanocarrier systems are promising in cancer treatment. They improve drug stability and facilitate controlled drug release. However, single-responsive nanocarriers still face insufficient tumor targeting and low efficacy. In this study, we synthesized folate-modified DSPE-PEOz nanomicelles with PEG chains and loaded them with magnetic iron particles and doxorubicin (DOX). Folic acid (FA) was employed as a ligand to target cancer cells actively. The nanomicelles are biocompatible and acid-sensitive drug carriers. Magnetic field-responsive nanoparticles enable moderately controlled magnetothermal therapy of tumors regardless of tumor location. The pH/magnetic field dual-responsive nanomicelles shed their PEG layer in response to tumor tissue acidity and react to magnetic fields through magnetothermal effects. In vitro and in vivo experiments demonstrated that the nanomicelles could efficiently target cancer cells, release drugs in response to pH changes, and enhance drug uptake through magnetothermal effects. The dual-responsive magnetic nanomicelles are expected to enhance the anti-cancer efficacy of chemo/magnetothermal synergistic therapy.

Hollow CuS nanoparticles equipped with hydroxyapatite/hyaluronic acid coating for NIR/pH dual-responsive drug delivery

The near-infrared (NIR)/pH dual-responsive nanoplatform shows great potential in remote photothermal therapy for tumor on account of the near-infrared window in biological tissue and the mild acidic environment in tumor cells. CuS nanoplatform has become a rising star in the field of photothermal agents due to its excellent NIR responsiveness and photostability. In this work, hollow CuS nanoparticles with high photothermal conversion efficiency (42.42 %) were synthesized through a novel surfactant micelle-assisted method. Then, CuS@hydroxyapatite (HAP)/hyaluronic acid (HA) nanoclusters with controllable drug release property were prepared by capping HAP and HA on the surface of CuS via electrostatic self-assembly approach. The hollow structure of CuS and the large specific surface area of HAP ensure an outstanding doxorubicin hydrochloride (DOX) loading efficiency of 99.2 % in CuS@HAP/HA nanoclusters. The introduction of HA effectively retards the initial burst release of DOX and ensures the excellent biocompatibility of nanoclusters. More importantly, CuS@HAP/HA displays distinct NIR/pH dual-responsive drug release properties owing to the excellent NIR responsiveness of hollow CuS and the gradual dissolution of HAP under acidic conditions. This work provides an environmentally benign method to prepare CuS-based nanoclusters with excellent NIR/pH responsive drug delivery properties, which has great potential in remote photothermal therapy.

Dual-responsive Drug Delivery System based on PEG-functionalized Pillararenes Containing Disulfide and Amido Bonds for Cancer Theranostics.

The construction of smart drug delivery system based on amphiphilic pillararenes with multiple responsiveness properties has become an important way to improve the efficacy of tumor chemotherapy. Herein, a new PEG-functionalized pillararene (EtP5-SS-PEG) containing disulfide and amido bonds was designed and synthesized, which has been used to construct a novel supramolecular nanocarrier through the host-guest interaction with a perylene diimide derivative (PDI-2NH4) and their supramolecular self-assembly. This nanocarrier showed good drugloading capability, and dual stimuli-responsiveness to enzyme and GSH (glutathione). After loading Doxorubicin (DOX), the prepared nanodrugs displayed efficient DOX release and outstanding cancer theranostics ability.

Dual-responsive targeted hollow mesoporous silica nanoparticles for cancer photodynamic therapy and chemotherapy

Surface modification of hollow mesoporous silica nanoparticles (HMSNs) with unique advantages are highly promising for drug delivery and have emerged for effective cancer treatment. In this study, functionalized nanoparticles for targeting and dual-responsive release of loaded doxorubicin hydrochloride (DOX·HCL) and indocyanine green (ICG) (labeled as ID@HCH). In addition, chitosan (CS) was conjugated onto the HMSNs as capping agents and then dialdehyde hyaluronic acid (HDA) was modified to endow the ability to target the CD44 receptor. The characterizations demonstrated that nanocarriers have been successfully constructed with excellent drug loading capacity (DL) and drug entrapment efficiency (EE). The in vitro DOX control release displayed pH/enzyme-response properties owing to the pH-dependent swelling effect of chitosan and the HDA degraded by hyaluronidases (HAase). Moreover, the results of in vitro cell experiments proved that the ID@HCH could inhibit the cancer cells viability via accurately targeting HepG2 cells and chemotherapy combined with photodynamic therapy. This study demonstrated that ID@HCH is a new promising dual-responsive drug delivery system for chemotherapy and photodynamic therapy.

Synergistic delivery of Imatinib through multifunctional nano-crystalline capsules, in response to redox environment for improved breast cancer therapy

Chondroitin anchored crystalline nano-capsules bearing Imatinib (IMT), and simvastatin (SMV) was developed using Poly (L-lactic acid) (PLLA) by two-step method, i.e., firstly, by synthesizing chondroitin (CSA) anchored simvastatin (SMV) using cystamine as a spacer (SMV-SS-CSA) for disulfide triggered glutathione (GSH) sensitive release and secondly, by developing phenyl boronic ester grafted Pluronic F68 (PEPF) for H2O2 responsive release. By combining these conjugates, we have prepared crystalline nano-capsules (CNs) for preferential targeting of CD44 receptors. The developed CNs were spherical when characterized through SEM, TEM, and AFM for surface morphology, while changes in particle size and crystalline structure were confirmed through Quasi-Elastic light scattering (QELS) and Wide Angle X-ray Scattering (WAXS). The enhanced cellular uptake was noted in chondroitin-modified nano-capsules IMT/SMV-SS-CSA@CNs compared to unmodified nano-capsules IMT+SMV@CNs. IMT/SMV-SS-CSA@CNs displayed significantly higher G2/M phase arrest (76.9%) than unmodified nano-capsules. The prototype formulation (IMT/SMV-SS-CSA@CNs) showed an overall improved pharmacokinetic profile in terms of both half-life and AUC0-α. When tested in the 4T1 subcutaneously injected tumor-bearing Balb/c mice model, the tumor growth inhibition rate of IMT/SMV-SS-CSA@CNs was significantly higher (91%) than the IMT+SMV combination. Overall, the findings suggest that the proposed dual responsive chondroitin-modified drug delivery could have a step forward in achieving spatial and temporal targeting at the tumor site.

PH/thermal dual-responsive multifunctional drug delivery system for effective photoacoustic imaging-guided tumor chemo/photothermal therapy.

The development of a combination of chemo/photothermal therapy could overcome the limitations of single-modality therapy and enhance therapeutic efficacy. In this study, a pH/thermal dual-responsive multifunctional drug delivery system with dual-drug loading and enhanced chemo/photothermal therapy is developed based on polydopamine-coated mesoporous silica-gold nanorods (PDA-AuNRs@MSN). Nanoscale mesoporous silica-gold nanorods encapsulating doxorubicin (DOX) are designed as a core and then modified by polydopamine. The PDA shell not only conjugates with another anticancer bortezomib (Btz) to form pH-sensitive bond through boronic acid and catechol but also acts as a gatekeeper to control the release of doxorubicin and enhance the photothermal effect. Such a nanocarrier not only acts as a contrast agent for PA imaging but also serves as a therapeutic agent for enhanced chemo/photothermal therapy. The DOX and Btz could be released in an on-demand mode under near-infrared light irradiation and acid environment. The tumor size and location could be observed via PA imaging after intravenous injection into 4T1-bearing mice. Compared with AuNRs@MSN, PDA-AuNRs@MSN exhibit an increased near-infrared (NIR) absorption at 808 nm and an enhanced photothermal effect. The integrated D/B-PDA-AuNRs@MSN nanoparticles show higher cell apoptosis and enhanced tumor treatment efficacy in vitro and in vivo in comparison with single chemotherapy or photothermal therapy. Combined together, D/B-PDA-AuNRs@MSN show pH/thermal-responsive controlled-release and synergistic chemo/photothermal therapy for tumor.

Dual-responsive antibiotic and baicalein co-delivery nanoparticles with enhanced synergistic antibacterial activity

Globally, due to the rapid development of bacterial resistance, bacterial infections lead to significant mortality and morbidity which require efficient strategies to eradicate these infections. Herein, we prepared a dual-responsive synergistic drug delivery nanoparticle carrier (NPS@Bai/Cip), which responds to sub-acid bacterial microenvironments and targets phosphatase or phospholipase at infection sites. Nanoparticles surfaces were positively (10.0 mV) charged under acidic conditions, leading to good bacterial adhesion and enhanced drug accumulation. NPS@Bai/Cip showed good antibacterial and anti-biofilm activity against drug-resistant Pseudomonas aeruginosa. NPS@Bai/Cip could inhibit the biofilm formation via affecting the swimming, swarming, and twitching motilities of P. aeruginosa. NPS@Bai/Cip was used to treat drug-resistance P. aeruginosa-induced infection in rats by improving wound healing and reducing inflammatory responses. Thus, NPS@Bai/Cip functioned as an antibacterial and antibiofilm agent with good potential for treating bacteria-induced infections.

PH/hyaluronidase dual responsive nano drug delivery systems for photothermal/chemotherapy combined treatment for non-small cell lung cancer

A biocompatible multifunctional nanocrystalline drug carrier system (RCDs-HA@AZD) with dual stimulation of pH and hyaluronidase has been developed for chemotherapy/photothermal combination therapy of non-small cell lung cancer (NSCLC).

Construction of a pH/Temperature dual-responsive drug delivery platform based on exfoliated MoS2 nanosheets for effective delivery of doxorubicin: Parametric optimization via central composite design

The aim of the current work was to develop drug delivery system for encapsulation and release of doxorubicin using exfoliated molybdenum disulfide nanosheets modified N-isopropyl acrylamide/methyl methacrylate. Here, glutamine was conjugated to the surface of molybdenum disulfide nanosheets. Several techniques such as Fourier transform infrared spectroscopy, X-ray diffraction, thermal gravimetric analysis, field emission scanning electron microscopy, and Zeta potential were applied to characterize the nanoadsorbent. Three important parameters of pH, contact time, and temperature were optimized by the response surface methodology technique. According to the central composite design, the maximum adsorption efficiency of 95% is attained at the pH = 8, contact time of 15 min, and temperature of 30 °C. The non-linear isotherms and kinetics sorption of drug onto nanoadsorbent can be excellently simulated by the Freundlich isotherm model and pseudo-second-order kinetic models, respectively. The dual-responsive nanocarrier indicated a slow release profile in simulated blood fluid at pH = 7.4 (T = 37 °C), whereas 98% of drug was released when nanocarrier were dissolved in pH = 5.6 (T = 50 °C) after 6 h, showing a sustained pH and temperature dependent drug release. The biocompatibility of nanocarrier was evaluated by MTT assay on KB cell line as a breast cancer modal cell.

Dual responsive block copolymer coated hollow mesoporous silica nanoparticles for glucose-mediated transcutaneous drug delivery

A self-regulated anti-diabetic drug release device mimicking pancreatic cells is highly desirable for the therapy of diabetes. Herein, a glucose-mediated dual-responsive drug delivery system, which combines pH- and H 2 O 2 -responsive block copolymer grafted hollow mesoporous silica nanoparticles (HMSNs) with microneedle (MN) array patch, has been developed to achieve self-regulated administration. The poly[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acrylate]- b -poly[2-(dimethylamino)ethyl methacrylate] (PPBEM- b -PDM) polymer serves as gate keeper to prevent drug release from the cavity of HMSNs at normoglycemic level. In contrast, the drug release rate is significantly enhanced upon H 2 O 2 and pH stimuli due to the chemical change of H 2 O 2 sensitive PPBEM block and acid responsive PDM block. Therefore, incorporation of anti-diabetic drug and glucose oxidase (GOx, which can oxidize glucose to gluconic acid and in-situ produce H 2 O 2 ) into stimulus polymer coated HMSNs results in a glucose-mediated MN device after depositing the drug-loaded nanoparticles into MN array patch. Both in vitro and in vivo results show this MN device presents a glucose mediated self-regulated drug release characteristic, which possesses a rapid drug release at hyperglycemic level but retarded drug release at normoglycemic level. The result indicates that the fabricated smart drug delivery system is a good candidate for the therapy of diabetes.

PH/Redox Dual-Responsive Drug Delivery System with on-Demand RGD Exposure for Photochemotherapy of Tumors.

Nanotechnology has been widely used in antitumor research. The complex physiological environment has brought significant challenges to the field of antitumor micelles. The ideal micelles must not only have an invisible surface to extend the circulation time but must also enhance the retention of drugs and cellular internalization at the tumor. A graded response micelle (RPPssD@IR780/DOC) was designed to self-assemble by cRGD-poly(β-amino esters)-polyethylene glycol-ss-distearoyl phosphatidylethanolamine (cRGD-PBAE-PEG-ss-DSPE) loaded with docetaxel (DOC) and IR-780 iodide (IR780). The micelles were designed to allow the PEG shell to prolong the blood circulation time in the body and effectively accumulate in the tumor. Subsequently, the acidic microenvironment of the tumor could transform the PBAE to hydrophilic, thereby increasing the size of micelles and exposing cyclic Arg-Gly-Asp (cRGD) peptides to increase the retention and cellular internalization of micelles in the tumor. After tumor cells had captured micelles, the high expression of glutathione in the cells prompted the release of DOC and IR780. Subsequently, the IR780 was stimulated by an 808-nm laser to generate local heat and reactive oxygen species (ROS) to synergize with DOC to treat the tumor. In vitro and in vivo experimental results suggested that RPPssD@IR780/DOC was a potential photochemical effective for the treatment of tumors with non-negligible antitumor activity and good biocompatibility. A dual-response pH/redox delivery system with on-demand RGD exposure was designed to achieve photochemotherapy of tumors with good biosafety and antitumor effects.

Liposomes embedded with PEGylated iron oxide nanoparticles enable ferroptosis and combination therapy in cancer.

Ferroptosis, an iron-dependent regulated cell death process driven by excessive lipid peroxides, can enhance cancer vulnerability to chemotherapy, targeted therapy and immunotherapy. As an essential upstream process for ferroptosis activation, lipid peroxidation of biological membranes is expected to be primarily induced by intrabilayer reactive oxygen species (ROS), indicating a promising strategy to initiate peroxidation by improving the local content of diffusion-limited ROS in the lipid bilayer. Herein, liposomes embedded with PEG-coated 3nm γ-Fe2O3 nanoparticles in the bilayer (abbreviated as Lp-IO) were constructed to promote the intrabilayer generation of hydroxyl radicals (•OH) from hydrogen peroxide (H2O2), and the integration of amphiphilic PEG moieties with liposomal bilayer improved lipid membrane permeability to H2O2 and •OH, resulting in efficient initiation of lipid peroxidation and thus ferroptosis in cancer cells. Additionally, Lp-IO enabled traceable magnetic resonance imaging and pH/ROS dual-responsive drug delivery. Synergistic antineoplastic effects of chemotherapy and ferroptosis, and alleviated chemotherapeutic toxicity, were achieved by delivering doxorubicin (capable of xCT and glutathione peroxidase inhibition) with Lp-IO. This work provides an efficient alternative for triggering therapeutic lipid peroxidation and a ferroptosis-activating drug delivery vehicle for combination cancer therapies.

One-pot self-assembly fabrication of chitosan coated hollow sphere for pH/ glutathione dual responsive drug delivery

Chitosan-coated poly (methacrylic acid) (PMAA) hollow spheres with 64 ± 3% drug loading capacity and low drug leakage (7 ± 2%, 54 h) were prepared through a novel one-pot two-step self-assembly process. Site-specific doxorubicin (DOX) loading and chitosan coating were achieved by electrostatic interaction to fulfill efficient drug loading and well-controlled drug release behavior. In vitro drug release profile revealed the pH and glutathione (GSH) dual responsive fast triggered drug release behavior, reaching 62 ± 3% during the first 10 h. And completely drug release could be achieved in 54 h. The high drug content and sensitive tumor microenvironment responsibility lead to similar anti-cancer efficiency with free doxorubicin in in vitro MTT assay. This self-assembly guided one-pot two-step fabrication process was proved to be an effective and convenient way to prepare the well-defined multi-layer structure and might be further employed in fabricating high-performance drug delivery systems.

A convergent fabrication of pH and redox dual-responsive hybrids of mesoporous silica nanoparticles for the treatment of breast cancer

Mesoporous silica nanoparticle (MSN), sodium hyaluronate (SH), silk fibroin (SS), and oxidized sodium carboxymethyl cellulose (O-CMC) hybrids were used to develop an intelligent drug delivery platform that may be employed for pH and redox-responsive bi-drug administration. The first drug, cytarabine (Cyt), was loaded with amino-functionalized mesoporous silica (MSN-NH2) encased by the hydrogel of cystamine (Cys) and SH cross-linked by amide bonds. Hydrophobic doxorubicin (DOX) was co-loaded with Cyt/MSN-NH2/SA in the hydrogel of SS and O-CMC in the Cyt- loaded hydrogel. Dual-responsive drug delivery may be achieved by encapsulating SS and O-CMC in a hydrogel, including Cyt/MSN-NH2/SA/DOX/SS/O-CMC, which has acyl hydrazone bonds (-HC = N) and disulfide bond (-S-S-) exchange reaction with glutathione (GSH). Compared to hydrogels encapsulating only one drug (Cyt or DOX), cell survival analysis revealed that the newly fabricated hydrogels have significantly greater chemotherapeutic efficacy. The cell proliferation of the fabricated nanoparticles was examined in MCF-7 and MDA-MB-231 cells, which indicates that the nanoparticles effectively kill the cancer cells without affecting non-cancerous cells. Further, we effectively investigated the morphological changes, and various biochemical staining methods examined nuclear fragmentation/condensation. Furthermore, the biosafety of the nanoparticles was investigated by the in vivo animal model, which reveals that they remarkably enhanced the safety profile in various organs. These outcomes demonstrated that this nanoparticle platform was a promising beneficial agent for improving breast cancer treatment.

Combined and Single Doxorubicin/Naproxen Drug Loading and Dual-Responsive pH/Ultrasound Release from Flexible Metal-Organic Framework Nanocarriers

In this study, the flexible aluminum-based MIL-53(Al) metal-organic framework was loaded with doxorubicin (DOX) and naproxen (NAP) and was examined as a promising pH/ultrasound dual-responsive drug delivery system. The two drugs were encapsulated in MIL-53(Al) individually to produce the DOX@MIL-53(Al) and NAP@MIL-53(Al) nanocarriers. They were also encapsulated as a dual-drug formulation to produce the DOX* + NAP*@MIL-53(Al) nanocarrier. The MOF nanoparticles were characterized using the Scanning Electron Microscopy (SEM), X-ray diffraction (XRD), Fourier Transform Infrared spectroscopy (FTIR), and Dynamic Light Scattering (DLS) techniques. In the case of the DOX@MIL, the nanocarriers’ drug Encapsulation Efficiency (EE) and Encapsulation Capacity (EC) were 92% and 16 wt.%, respectively, whereas, in the case of NAP@MIL-53(Al), the average NAP EE and EC were around 97.7% and 8.5 wt.%, respectively. On the other hand, in the DOX* + NAP*@MIL-53(Al) nanoparticles, the average DOX* EE and EC were 38.9% and 6.22 wt.%, respectively, while for NAP*, the average EE and EC were 70.2% and 4.49 wt.%, respectively. In vitro release experiments demonstrated the good pH and Ultrasound (US) dual-responsiveness of these nanocarriers, with a maximum US-triggered DOX and NAP release, at a pH level of 7.4, of approximately 53% and 95%, respectively. In comparison, the measured release was around 90% and 36% at pH 5.3 for DOX and NAP, respectively. In the case of the dualdrug formulation, the nanocarrier displayed similar pH/US dual-responsive behavior. Finally, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) results confirmed the biocompatibility and low cytotoxicity of MIL-53(Al) at concentrations up to 1000 μg/ml.

A dual-responsive hyaluronic acid nanocomposite hydrogel drug delivery system for overcoming multiple drug resistance

Chemotherapy is restricted by efficient drug outflow due to the multiple drug resistance (MDR) in heterogenous nature of tumor. Herein, we present a dual-responsive hyaluronic acid (HA) nanocomposite hydrogel that can not only response to the tumor microenvironment but also enhance chemotherapy. This HA hydrogel consists of a core-shell SiO2 (GOD@SiO2-Arg) and mesoporous silica nanoparticles (MSNs) with doxorubicin (DOX) as the cargo (DOX@MSN). It could rapidly release the GOD@SiO2-Arg nanoparticles at the low pH tumor-specific environment due to the cleavage of imine bond. GOD@SiO2-Arg activated by over-expressed glutathione (GSH) in tumor cells releases GOD due to the cleavage of disulfide bonds, which could oxidize glucose to produce hydrogen peroxide (H2O2) for in situ NO generation via reaction between Arg and H2O2. The validity of this study might provide a method to modulate the tumor microenvironment for enhancing chemotherapy.

Magnetic mesoporous silica nanoparticles mediated redox and pH dual-responsive target drug delivery for combined magnetothermal therapy and chemotherapy

A combination of multiple therapies is conducive to the treatment efficacy of cancer. Chemotherapy combined with magnetothermal therapy provides an outstanding synergy for cancer treatment. In this study, magnetic mesoporous silica nanoparticles (MMSN) were developed as a multipurpose nanoplatform for doxorubicin (DOX) delivery and magnetothermal treatment of cancer simultaneously. The MMSN were composed of Fe3O4 and mesoporous silica as core and shell. The folic acid (FA) linked chitosan (CS) was conjugated at the outlets of MMSN (MMSN-SS-FA) using disulfide bonds to avert the premature release of the drug in mesopores of MMSN, target folate receptor-overexpressed cancer cells and increase the safety and physiological stability of MMSN. The temperature of the MMSN suspension could be elevated from 37 °C to 45 °C at the concentration of 1 mg/mL under an alternating magnetic field (AMF), which exceeded the tumor ablating temperature. The in vitro drug release proved that the DOX/MMSN-SS-FA displayed the redox/pH/AMF multiple-responsive release. The cellular uptake results indicated that the MMSN-SS-FA could target folate receptor-overexpressed HeLa cells. The DOX/MSNS-SS-FA with AMF had the highest cytotoxicity at the equivalent drug concentration towards HeLa cells with a combination index (CI) of 0.276, demonstrating the synergistic treatment effect of chemotherapy and magnetic-thermal therapy. Meanwhile, the DOX/MMSN-SS-FA+AMF showed the strongest tumor inhibitory effect of 84 % on tumor growth. Therefore, the constructed MMSN-SS-FA with good biocompatibility and biosafety can act as multifunctional nano-platforms for tumor treatment.

Preparation of MSNs@Keratin as pH/GSH dual responsive drug delivery system

Designing a drug delivery system that is responsive in a tumor microenvironment is important to potentiate the efficacy and reduce the side effects of antitumor drugs. In this study, the surface of mesoporous silica nanoparticles (MSNs) were aminated with 3-aminopropyl triethoxysilane (APTES) and then coupled with keratin, as a gatekeeper, to afford MSNs-NH2@Keratin. The average sizes and morphologies of MSNs and MSNs-NH2@Keratin were characterized with dynamic light scattering and transmission electron microscopy, respectively. The loading content and encapsulation efficiency of doxorubicin (DOX) were calculated to be 17.1 ± 1.7% and 71.3 ± 2.1%. Drug-loaded MSNs-NH2@Keratin exhibited pH and glutathione (GSH) dual responsiveness under tumor microenvironment. The nanoparticles could be uptaken by tumor cells to effectively inhibit tumor cell growth. Moreover, the sizes of nanoparticle were stable in the serum. Collectively, our findings demonstrated the potential of DOX-loaded MSNs-NH2@Keratin in the treatment of cancer.

PH- and H2O2-sensitive drug delivery system based on sodium xanthate: Dual-responsive supramolecular vesicles from one functional group

Nano-drug delivery systems with multiple stimulus-responsive capabilities have superior response performance and efficient drug release. Nevertheless, it is sophisticated to construct multiple stimulus-responsive systems where the two or more functional groups need to be introduced simultaneously. Xanthate, one functional group with pH and H2O2 stimulus responsiveness, has significant potential applications for building dual-responsive drug delivery system. Herein, we present a novel dual stimuli-responsive supramolecular drug delivery system by using sodium xanthate derivative (SXD) as guest molecule and quaternary ammonium capped pillar[5]arene (QAP5) as host molecule through host-guest interaction on the basis of electrostatic interaction. The amphiphile QAP5⊃SXD could self-assemble into vesicles to efficiently load the anti-cancer drug DOX. The experimental results showed that QAP5⊃SXD nanoparticles could achieve efficient drug delivery and controlled release in the tumor microenvironment. Cytotoxicity experiments proved that DOX@QAP5⊃SXD nanoparticles could significantly improve the anticancer efficiency of free DOX on cancer cells. The present study provides an efficient strategy to develop supramolecular nanocarriers with dual-responsiveness in one functional group for controlled drug release.

Construction of a dual-responsive dual-drug delivery platform based on the hybrids of mesoporous silica, sodium hyaluronate, chitosan and oxidized sodium carboxymethyl cellulose

An intelligent drug delivery platform based on the hybrids of mesoporous silica nanoparticles (MSN), sodium hyaluronate (HA), chitosan (CS) and oxidized sodium carboxymethyl cellulose (oxCMC) is developed, which can be used for dual-responsive dual-drug delivery. Hydrophilic cytarabine (Cyt) is first loaded into the mesopores of the aminated MSN (NH2-MSN), which is encapsulated by the hydrogel of HA and cystamine (Cys) crosslinked via amidation. The Cyt encapsulated hydrogel which is denoted as Cyt/NH2-MSN/HA is co-encapsulated with hydrophobic methotrexate (MTX) into the hydrogel of CS and oxCMC resulted from Schiff base reaction. Since the acylhydrazone bonds (–HC=N–) between CS and oxCMC are sensitive to pH and the disulfide bonds (–S–S–) in Cys are sensitive to glutathione (GSH), the resultant dual-drug encapsulated hydrogel, denoted as Cyt/NH2-MSN/HA/MTX/CS/oxCMC, can be used for dual-responsive (pH and GSH) drug delivery. The results of cell viability demonstrate that the developed dual-drug encapsulated hydrogel has significantly higher efficacy of chemotherapy than that of single-drug (MTX or Cyt) encapsulated hydrogel.