Dual-responsive Drug Release Research Articles

Design and Antimalarial Evaluation of Polydopamine-Modified Methyl Artelinate Nanoparticles.

Targeted nanodrug delivery systems are highly anticipated for the treatment of malaria. It is known that Plasmodium can induce new permeability pathways (NPPs) on the membrane of infected red blood cells (iRBCs) for their nutrient uptake. The NPPs also enable the uptake of nanoparticles (NPs) smaller than 80 nm. Additionally, Plasmodium maintains a stable, slightly acidic, and reductive internal environment with higher glutathione (GSH) levels. Based on this knowledge, methyl artelinate (MA, a prodrug-like derivative of dihydroartemisinin) nanoparticles (MA-PCL-NPs) were developed using poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-PCL) by a thin-film dispersion method and were further coated with polydopamine (PDA) to obtain MA-PCL@PDA-NPs with a particle size of ∼30 nm. The biomaterial PDA can be degraded in slightly acidic and reductive environments, thereby serving as triggers for drug release. MA could generate reactive oxygen species and decrease GSH levels, consequently causing parasite damage. The in vitro release experiment results indicated that the cumulative release percentage of MA from MA-PCL@PDA-NPs was considerably higher in phosphate buffer with 10 mM GSH at pH 5.5 (88.10%) than in phosphate buffer without GSH at pH 7.4 (16.98%). The green fluorescence within iRBCs of coumarin 6, the probe of NPs (C6-PCL@PDA-NPs), could be reduced significantly after adding the NPP inhibitor furosemide (p < 0.001), which demonstrated that MA-PCL@PDA-NPs could be ingested into iRBCs through NPPs. In vivo antimalarial pharmacodynamics in Plasmodium berghei K173-bearing mice showed that the inhibition ratio of MA-PCL@PDA-NPs (93.96%) was significantly higher than that of commercial artesunate injection (AS-Inj, 63.33%). The above results showed that the developed MA-PCL@PDA-NPs possessed pH-GSH dual-responsive drug release characteristics and targeting efficacy for iRBCs, leading to higher antimalarial efficacy against Plasmodium.

Hyaluronic acid/chitosan microcapsules capped with hollow CuS nanoparticles for NIR/pH dual-responsive drug release

Hollow natural polysaccharide microcapsules have broad applications in drug delivery field due to their excellent biocompatibility and drug loading efficiency. In this paper, pH/near-infrared (NIR) dual-responsive microcapsules composed of hyaluronic acid (HA), chitosan (CS) and hollow CuS (HA/CS/HA@CuS) had been fabricated via a layer-by-layer (LbL) approach. The negative charge, rough surface and hollow structure of microcapsules are very favorable for loading positively charged DOX. As a result, hollow microcapsules display a high drug loading efficiency of 91.15 %. The variation in the degree of amino ionization at different pH values leads to the changes in the electrostatic force between CS/HA multilayers, resulting in the structural change in microcapsules. Therefore, microcapsules exhibit significant pH-responsive drug release properties. In addition, hollow CuS nanoparticles with excellent photothermal conversion ability are capped on the multilayer surface, enabling microcapsules to exhibit excellent NIR-responsive drug delivery properties. Overall, hyaluronic acid/chitosan-based hollow microcapsules with notable pH/NIR dual-responsiveness have been prepared, which can be used as a potential drug carrier for controlled drug delivery and photothermal chemical combination therapy.

Hybrid Liposome-MSN System with Co-Delivering Potential Effective Against Multidrug-Resistant Tumor Targets in Mice Model.

RNA interference (RNAi) stands as a widely employed gene interference technology, with small interfering RNA (siRNA) emerging as a promising tool for cancer treatment. However, the inherent limitations of siRNA, such as easy degradation and low bioavailability, hamper its efficacy in cancer therapy. To address these challenges, this study focused on the development of a nanocarrier system (HLM-N@DOX/R) capable of delivering both siRNA and doxorubicin for the treatment of breast cancer. The study involved a comprehensive investigation into various characteristics of the nanocarrier, including shape, diameter, Fourier transform infrared (FT-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS), encapsulation efficiency, and drug loading. Subsequently, in vitro and in vivo studies were conducted on cytotoxicity, cellular uptake, cellular immunofluorescence, lysosome escape, and mouse tumor models to evaluate the efficacy of the nanocarrier in reversing tumor multidrug resistance and anti-tumor effects. The results showed that HLM-N@DOX/R had a high encapsulation efficiency and drug loading capacity, and exhibited pH/redox dual responsive drug release characteristics. In vitro and in vivo studies showed that HLM-N@DOX/R inhibited the expression of P-gp by 80%, inhibited MDR tumor growth by 71% and eliminated P protein mediated multidrug resistance. In summary, HLM-N holds tremendous potential as an effective and targeted co-delivery system for DOX and P-gp siRNA, offering a promising strategy for overcoming MDR in breast cancer.

Self-assembled copper-based nanoparticles for enzyme catalysis-enhanced chemodynamic/photodynamic/antiangiogenic tritherapy against hepatocellular carcinoma

As an emerging cancer treatment strategy, reactive oxygen species-based tumor catalytic therapies face enormous challenges due to hypoxia and the overexpression of glutathione (GSH) in the tumor microenvironment. Herein, a self-assembled copper-based nanoplatform, TCCHA, was designed for enzyme-like catalysis-enhanced chemodynamic/photodynamic/antiangiogenic tritherapy against hepatocellular carcinoma. TCCHA was fabricated from Cu2+, 3,3′-dithiobis (propionohydrazide), and photosensitizer chlorine e6 via a facile one-pot self-assembly strategy, after which an aldehyde hyaluronic acid was coated, followed by loading of the antivascular drug AL3818. The obtained TCCHA nanoparticles exhibited pH/GSH dual-responsive drug release behaviors and multienzymatic activities, including Fenton, glutathione peroxidase-, and catalase-like activities. TCCHA, a redox homeostasis disruptor, promotes ⋅OH generation and GSH depletion, thus increasing the efficacy of chemodynamic therapy. TCCHA, which has catalase-like activity, can also reinforce the efficacy of photodynamic therapy by amplifying O2 production. In vivo, TCCHA efficiently inhibited tumor angiogenesis and suppressed tumor growth without apparent systemic toxicity. Overall, this study presents a facile strategy for the preparation of multienzyme-like nanoparticles, and TCCHA nanoparticles display great potential for enzyme catalysis-enhanced chemodynamic/photodynamic/antiangiogenic triple therapy against cancer.Graphical

PH/GSH dual-responsive nanoparticle for auto-amplified tumor therapy of breast cancer

Breast cancer remains a malignancy that poses a serious threat to human health worldwide. Chemotherapy is one of the most widely effective cancer treatments in clinical practice, but it has some drawbacks such as poor targeting, high toxicity, numerous side effects, and susceptibility to drug resistance. For auto-amplified tumor therapy, a nanoparticle designated GDTF is prepared by wrapping gambogic acid (GA)-loaded dendritic porous silica nanoparticles (DPSNs) with a tannic acid (TA)-Fe(III) coating layer. GDTF possesses the properties of near-infrared (NIR)-enhanced and pH/glutathione (GSH) dual-responsive drug release, photothermal conversion, GSH depletion and hydroxyl radical (·OH) production. When GDTF is exposed to NIR laser irradiation, it can effectively inhibit cell proliferation and tumor growth both in vitro and in vivo with limited toxicity. This may be due to the synergistic effect of enhanced tumor accumulation, and elevated reactive oxygen species (ROS) production, GSH depletion, and TrxR activity reduction. This study highlights the enormous potential of auto-amplified tumor therapy.

Construction and performance of photo-thermal dual-responsive drug release patches with sandwich-structure based on electrospun

Designing and preparing smart drug release systems suitable for application are important in medicine. In the present work, sandwich-structured drug patches with photo-thermal dual-responsive properties were designed and fabricated based on electrospinning technology and post-assembly. The target sandwich-structured patch comprised of a UV-responsive electrospun membrane and a skin-contacting electrospun gel membrane. The porous structure of the electrospun membrane and electrospun gel endowed the patch’s excellent moisture retention and gas permeability which could ensure the breathe of the skin and prevent from hurting of permeating water at the same time. Moreover, the viscosity properties of the skin contacting layer caused the patches’ good adhesion properties, resulting in improved the long term adheres to the skin. Then drugs and temperature-sensitive substances were clamped in the interlayers of the sandwich-structured patch which was sealed by polyvinylpyrrolidone-silica (PVP-SiO2) electrospinning solution. Thus, the sandwich-structured patches not only exhibited photo-thermal responsive properties but also presented heightened drug carrying capacity and versatile applicability across various drugs.

A carrier-free tri-component nanoreactor for multi-pronged synergistic cancer therapy

Non-invasive therapies such as photodynamic therapy (PDT) and chemodynamic therapy (CDT) have received wide attention due to their low toxicity and side effects, but their efficacy is limited by the tumor microenvironment (TME), and monotherapy cannot achieve satisfactory efficacy. In this work, a multifunctional nanoparticle co-assembled from oleanolic acid (OA), chlorin e6 (Ce6) and hemin was developed. The as-constructed nanoparticle named OCH with diameters of around 130 nm possessed good biostability, pH/GSH dual-responsive drug release properties, and remarkable cellular internalization and tumor accumulation capabilities. OCH exhibited prominent catalytic activities to generate •OH, deplete GSH, and produce O2 to overcome the hypoxia TME, thus potentiating the photodynamic and chemodynamic effect. In addition, OCH can induce the occurrence of ferroptosis in both ferroptosis-sensitive and ferroptosis-resistant cancer cells. The multi-pronged effects of OCH including hypoxia alleviation, GSH depletion, ferroptosis induction, CDT and PDT effects jointly facilitate excellent anticancer effects in vitro and in vivo. Hence, this work will advance the development of safe and effective clinically transformable nanomedicine by employing clinically-applied agents to form drug combinations for efficient multi-pronged combination cancer therapy.

Synergistic chemo-photothermal therapy using gold nanorods supported on thiol-functionalized mesoporous silica for lung cancer treatment

Cancer therapy necessitates the development of novel and effective treatment modalities to combat the complexity of this disease. In this project, we propose a synergistic approach by combining chemo-photothermal treatment using gold nanorods (AuNRs) supported on thiol-functionalized mesoporous silica, offering a promising solution for enhanced lung cancer therapy. To begin, mesoporous MCM-41 was synthesized using a surfactant-templated sol–gel method, chosen for its desirable porous structure, excellent biocompatibility, and non-toxic properties. Further, thiol-functionalized MCM-41 was achieved through a simple grafting process, enabling the subsequent synthesis of AuNRs supported on thiol-functionalized MCM-41 (AuNR@S-MCM-41) via a gold-thiol interaction. The nanocomposite was then loaded with the anticancer drug doxorubicin (DOX), resulting in AuNR@S-MCM-41-DOX. Remarkably, the nanocomposite exhibited pH/NIR dual-responsive drug release behaviors, facilitating targeted drug delivery. In addition, it demonstrated exceptional biocompatibility and efficient internalization into A549 lung cancer cells. Notably, the combined photothermal-chemo therapy by AuNR@S-MCM-41-DOX exhibited superior efficacy in killing cancer cells compared to single chemo- or photothermal therapies. This study showcases the potential of the AuNR@S-MCM-41-DOX nanocomposite as a promising candidate for combined chemo-photothermal therapy in lung cancer treatment. The innovative integration of gold nanorods, thiol-functionalized mesoporous silica, and pH/NIR dual-responsive drug release provides a comprehensive and effective therapeutic approach for improved outcomes in lung cancer therapy. Future advancements based on this strategy hold promise for addressing the challenges posed by cancer and transforming patient care.

Bimetallic Gold/Silver and Bioactive Camptothecin Hybrid Nanoparticles for Eradication of Cancer Stem Cells in a Combination Manner.

The defeat of cancer is still a challenge due to the existence of cancer stem cells (CSCs) because they resist conventional chemotherapy via multifactor regulated mechanisms. Consequently, one-dimensional action toward CSCs cannot work. Herein, we used rationally designed hybrid nanoparticles as a combined cancer therapy, hoping to form a multidimensional control network. In this paper, gold/silver alloy nanoparticle decorated camptothecin nanocrystals were formulated according to complementary anti-CSC mechanisms from gold, silver, and organic drug. This smart drug formulation could combine chemotherapy and thermotherapy, target different tumor sites, and demonstrate versatile toxicity profiles from each component. Major results indicated that this nanosystem demonstrated indiscriminately effective cytotoxic/proapoptotic/necrotic activity against bulk MCF-7 cells and their CSC subpopulation, in particular under laser ablation. Moreover, this nanosystem displayed enhanced antineoplastic activity against CSC spheroids, resulting in a significant reduction in their number and size, that is, their self-renewal capacity. All the results indicated that CSCs upon treatment of these new hybrid nanoparticles underwent reduced stemness and conversion from the original quiescent state and recovered their sensitivity toward chemotherapy. The relevant anticancer mechanism was ascribed to NIR-pH dual responsive drug release, synergistic/combined thermo-chemotherapy of organic drug and inorganic alloy nanoparticles, enhanced cellular uptake mediated by alloy nanoparticles, and Ag+-induced biomembrane damage. This thermo-chemotherapy platform provides a new combinatorial strategy for inorganic and organic agents in the complete elimination of CSCs.

Multilayer nanodrug delivery system with spatiotemporal drug release improves tumor microenvironment for synergistic anticancer therapy

The inflammatory response is one of the general symptoms that accompany tumorigenesis, the pro-inflammatory factors cyclooxygenase-2 (COX-2) and COX-2-derived prostaglandin-2 (PGE-2) in the inflammatory environment surrounding tumors possess promoting tumor development, metastasis and angiogenesis effects. In addition, the hypoxic environment of tumors severely limits the effectiveness of photodynamic therapy (PDT). In this study, a universal extracellular-intracellular ‘on-demand’ release nanomedicine DOX@PDA-ICG@MnO2@GN-CEL was developed for the combined fight against malignant tumors using a spatiotemporal controlled gelatin coated polydopamine (PDA@GN) as the carrier and loaded with the chemotherapeutic drug doxorubicin (DOX), the photosensitizer indocyanine green (ICG), the PDT enhancer MnO2 and the anti-inflammatory drug celecoxib (CEL) individually. Our results showed that DOX@PDA-ICG@MnO2@GN-CEL could release CEL extracellularly by matrix metalloproteinase-2 response and inhibit the COX-2/PGE-2 pathway, reduce chemotherapy resistance and attenuate the concurrent inflammation. After entering the tumor cells, the remaining DOX@PDA-ICG@MnO2 released DOX, ICG and MnO2 intracellularly through PDA acid response. MnO2 promoted the degradation of endogenous H2O2 to generate oxygen under acidic conditions to alleviate the tumor hypoxic environment, enhance PDT triggered by ICG. PDA and ICG exhibited photothermal therapy synergistically, and DOX exerted chemotherapy with reduced chemotherapy resistance. The dual responsive drug release switch enabled the chemotherapeutic, photothermal, photodynamic and anti-inflammatory drugs precisely acted on different sites of tumor tissues and realized a promising multimodal combination therapy.

Combined Photothermal Chemotherapy for Effective Treatment Against Breast Cancer in Mice Model.

Breast cancer ranks among the most prevalent cancers in women, characterized by significant morbidity, disability, and mortality. Presently, chemotherapy is the principal clinical approach for treating breast cancer; however, it is constrained by limited targeting capability and an inadequate therapeutic index. Photothermal therapy, as a non-invasive approach, offers the potential to be combined with chemotherapy to improve tumor cellular uptake and tissue penetration. In this research, a mesoporous polydopamine-coated gold nanorod nanoplatform, encapsulating doxorubicin (Au@mPDA@DOX), was developed. This nanoplatform was constructed by surface coating mesoporous polydopamine (mPDA) onto gold nanorods, and doxorubicin (DOX) was encapsulated in Au@mPDA owing to π-π stacking between mPDA and DOX. The dynamic diameter, zeta potential, absorbance, photothermal conversion ability, and drug release behavior were determined. The cellular uptake, cytotoxicity, deep penetration, and anti-tumor effects were subsequently investigated in 4T1 cells. After that, fluorescence imaging, photothermal imaging and pharmacodynamics studies were utilized to evaluate the anti-tumor effects in tumor-bearing mice model. This nanoplatform exhibited high drug loading capacity, excellent photothermal conversion and, importantly, pH/photothermal dual-responsive drug release behavior. The in vitro results revealed enhanced photothermal-facilitated cellular uptake, drug release and tumor penetration of Au@mPDA@DOX under near-infrared irradiation. In vivo studies confirmed that, compared with monotherapy with either chemotherapy or photothermal therapy, the anti-tumor effects of Au@mPDA@DOX are synergistically improved. Together with good biosafety and biocompatibility, the Au@mPDA@DOX nanoplatform provides an alternative method for safe and synergistic treatment of breast cancer.

Self-assembled hollow CuS@AuNRs/PDA nanohybrids with synergistically enhanced photothermal efficiency.

The design of multifunctional nanocarriers with enhanced photothermal efficiency is of great significance for the photothermal therapy of cancer. In this study, hollow CuS@gold nanorods/polydopamine (HCuS@AuNRs/PDA) nanohybrids with synergistically enhanced photothermal efficiency were prepared by electrostatic self-assembly method. The high photothermal conversion efficiency of HCuS@AuNRs (55.88%) is attributed to the interfacial electron transfer between CuS and AuNRs, as well as the increase in free charge carrier concentration. The excellent adhesion performance and strong negative charge of PDA ensure a high doxorubicin hydrochloride (DOX) loading efficiency of 96.08% for HCuS@AuNRs/PDA. In addition, HCuS@AuNRs/PDA reveals outstanding NIR/pH dual-responsive drug release properties owing to the weakened interaction between PDA and DOX in acidic media and the distinct NIR responsiveness of HCuS@AuNRs. In vitro cell viability results confirm that HCuS@AuNRs/PDA could efficiently kill tumor cells under the dual effect of acidic media and NIR laser. This study presents a novel nanocarrier with synergistically enhanced NIR photothermal responsiveness and high drug loading capacity, which provides a versatile platform in intelligent drug release and photothermal therapy.

Biosynthesis of Quercetin-Loaded Melanin Nanoparticles for Improved Antioxidant Activity, Photothermal Antimicrobial, and NIR/pH Dual-Responsive Drug Release.

Quercetin (QCT) is a promising dose-dependent nutraceutical that usually suffers from poor water solubility and low bioavailability issues. In this work, a novel QCT-loaded nanoscale delivery system was constructed based on the oxidative self-polymerization of melanin (Q@MNPs). The FT-IR, XRD, and Zeta potential analyses confirmed that QCT was successfully absorbed on the melanin nanoparticles (MNPs) via Π-Π and hydrogen bonding interactions. The encapsulation efficiency and particle size of Q@MNPs were 43.78% and 26.68 nm, respectively. Q@MNPs improved the thermal stability of QCT and the antioxidant properties in comparison to MNPs. Meanwhile, Q@MNPs presented fantastic photothermal conversion capacity and stability triggered by the NIR laser, which significantly enhanced the antibacterial capability with a sterilization rate of more than 98% against E. coli and S. aureus. More importantly, Q@MNPs exhibited NIR/pH dual-responsive drug release behavior and good biocompatibility (at concentrations of < 100 μg/mL). Thus, Q@MNPs show promising prospects for flavonoid delivery.

Size-tunable nanogels for cascaded release of metronidazole and chemotherapeutic agents to combat Fusobacterium nucleatum-infected colorectal cancer

Bacteria play important roles in tumor formation, growth and metastasis through downregulating immune response and initiating drug resistance. Herein, size-tunable nanogels (NGs) have been developed to address the existing size paradox in tumor accumulation, intratumoral penetration and intracellular release of therapeutics for the treatment of Fusobacterium nucleatum (F. nucleatum)-infected colorectal cancer. Zinc-imidazolate frameworks with doxorubicin (DOX) loading and folate grafting (f-ZIFD) were mixed with metronidazole (MET) and encapsulated in NGs through thiol-ene click crosslinking of sulfhydryl hyaluronan, sulfhydryl alginate and 4-arm poly(ethylene glycol) acrylate. Hyaluronidase-initiated matrix degradation causes NG swelling to release sufficient MET and maintains a large size for an extended time period, and the gradually discharged f-ZIFD nanoparticles (NPs) from NGs exhibit acid-responsive intracellular release of DOX after folate-mediated internalization into tumor cells. The encapsulation into NGs significantly enhances the bioavailability and increases half-lives of MET and DOX by around 20 times. In the F. nucleatum-infected tumor model, the extended retention of swollen NGs and the efficient tumor infiltration and cellular uptake of the discharged f-ZIFD NPs cause 6 times higher DOX levels in tumors than that of free DOX administration. F. nucleatum promotes tumor cell proliferation and tumor growth, and the cascaded releases of MET and f-ZIFD NPs eliminate F. nucleatum to effectively inhibit tumor growth with a significant extension of animal survival. Thus, the hyaluronidase-mediated NG expansion and dual-responsive cascaded drug release have overcome challenges in the release regimen and size paradox of drug delivery carriers to combat bacteria-infected cancer.

In situ growth of MoS2@AuNRs nanoparticles with synergistically enhanced NIR response for controlled drug release

MoS2 nanosheets have received a lot of favor in biomedical applications due to their outstanding near-infrared (NIR) responsiveness. However, the poor aqueous dispersibility of MoS2 limits their biomedical application. In this paper, in-situ growth method was applied to integrate gold nanorods (AuNRs) with MoS2, and then MoS2 @AuNRs/HAP/PDA (denoted as MAHP) was prepared by introducing hydroxyapatite (HAP) and polydopamine (PDA) into MoS2 @AuNRs (MA) via self-assembly approach. In-situ grown MA inhibited the aggregation of MoS2 due to the insertion of AuNRs between MoS2 nanolayers. Therefore, MA revealed excellent aqueous dispersibility and synergistically enhanced NIR photothermal responsiveness (42.16% of photothermal conversion efficiency). In addition, MAHP exhibited outstanding DOX loading capacity (80%) and distinct pH-/NIR- dual responsive drug release properties, owing to the structural collapse of HAP in acidic medium and the excellent NIR responsiveness of MA. In vitro cell viability results revealed that MAHP could effectively kill MCF-7 cells under the dual effect of NIR laser irradiation and acidic medium. This paper presents a feasible process to prepare MoS2-based nanoparticles with NIR/pH dual-responsive release properties, which shows great potential in controlled photothermal therapy field.

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.

Tuning stimuli-responsive properties of alginate hydrogels through layer-by-layer functionalization for dual-responsive dual drug release

This study aimed to understand the effect of layer-by-layer (LbL) modification on the stimuli-responsive properties of physical alginate (ALG) hydrogels and examine the potential of LbL-coated hydrogels as dual responsive, dual drug releasing platforms for antibacterial applications. ALG hydrogels were functionalized through LbL self-assembly using temperature-responsive poly(2-isopropyl-2-oxazoline) (PiPOX) and pH-responsive tannic acid (TA). Ciprofloxacin (CIP) and Curcumin (CUR) were used as model hydrophilic and hydrophobic drugs, respectively. CIP was included in the hydrogel during LbL process, whereas CUR was incorporated into the hydrogel through gelation in the presence of CUR-loaded CaCO3 microparticles. The effect of LbL modification on the stimuli-responsive swelling, stability and drug release properties of hydrogels was examined in comparison with bare hydrogels. We have shown that LbL modification resulted in a partial loss of solid content from the hydrogel, leading to a greater swelling. In addition, LbL modification imparted temperature-responsiveness to ALG hydrogel and provided enhanced CIP release upon increasing the temperature at pH 7.4. On the other hand, LbL-coated hydrogels displayed minimal CIP release at pH 5.5 regardless of the temperature. The antibacterial activity of LbL-coated hydrogels was greater at pH 7.4 than pH 5.5 against both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacteria. The combination of CIP and CUR provided enhanced antibacterial effect on the inhibition of E.coli growth at both pH 7.4 and pH 5.5. This effect became more remarkable as the CIP concentration was decreased at a constant CUR concentration in the hydrogels. However, the combinatorial effect of CIP and CUR was not observed with S. aureus. Overall, these results may be promising for wound healing applications where drug release is triggered when the pH becomes alkaline in the presence of bacterial colonization.

MOF/polypeptide hybrid nanocomposites with pH/lipase dual responsive drug release and photodynamic effect for combination treatment of drug-resistant bacterial infection

Multi-drug resistant (MDR) bacterial infection has become one of the most serious health issues due to its high mortality rate. To address this problem, a novel metal–organic framework (MOF)/polypeptide hybrid nanocomposite was synthesised for the combined chemo-photodynamic therapy of MDR bacterial infection. A lipase-sensitive crosslinker was used to prepare the crosslinked polypeptide outer shell of the nanocomposite, and ciprofloxacin (CIP) and methylene blue (MB) were incorporated in the zeolite imidazole framework (ZIF)/poly-γ-glutamic acid (PGA) nanocomposites to form the combined therapeutic system (ZIF/PGA-C/M) for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). The ZIF/PGA-C/M displayed a negative surface charge of −11.2 mV at physiological pH, indicating improved structural stability and biocompatibility. The pH/lipase dual responsive drug release showed that up to 99.4% CIP and 76.0 % MB were released at pH 5.5 in the presence of lipase from the ZIF/PGA-C/M. Moreover, the incorporated MB can effectively generate singlet oxygen (1O2) to kill the bacteria by a photodynamic effect under NIR irradiation. Remarkably, ZIF/PGA-C/M showed an efficient inhibition rate towards MRSA in both planktonic and biofilm phenotypes, and a synergistic therapeutic effect against MRSA infection in the mice model of skin infection.

Chitosan/poly (ethylene oxide) nanofiber sponge with dual-responsive drug release and excellent antibacterial property

An ideal wound dressing can absorb wound exudate in time, and has the advantages of moisture permeability, oxygen permeability, rapid hemostatic performance, antibacterial and low-toxic, which are the key to wound healing. However, traditional wound dressings exist structural and functional defects, especially in controlling bleeding and active wound protection. Herein, a novel three-dimensional chitosan/ poly (ethylene oxide) sponge dressing (3D CS/PEO sponge-ZPC) consists of CS/PEO nanofiber sponge (carrier unit), Zn metal-organic framework grown in-situ (Zn-MOF, drug loading unit and antibacterial unit), curcumin (CUR, antibacterial unit), and poly[(N-isopropylacrylamide)-co-(methacrylic acid)] (P(NIPAM-co-MAA), ‘gatekeepers’ unit) to promote the wound healing by absorb exudate in time, accelerate hemostasis and inhibit bacteria growth. Due to the unique structure of the as-prepared 3D CS/PEO sponge-ZPC was endowed with smart stimuli-responsive drug release mode, rapid hemostatic performance and strong antibacterial property. The result of CUR release showed smart “ON-OFF” drug release mode. Antibacterial results verified strong antibacterial property up to 99.9 %. Hemolysis test showed that hemolysis ratio of 3D CS/PEO sponge-ZPC met the acceptable standard. The rapid hemostatic property was demonstrated by hemostatic test. High wound healing effect was confirmed in vivo. These results provide an important research basis for the design of new smart dressing.

NIR-Cleavable and pH-Responsive Polymeric Yolk-Shell Nanoparticles for Controlled Drug Release.

Responsive drug release and low toxicity of drug carriers are important for designing controlled release systems. Here, a double functional diffractive o-nitrobenzyl, containing multiple electron-donating groups as a crosslinker and methacrylic acid (MAA) as a monomer, was used to decorate upconversion nanoparticles (UCNPs) to produce robust poly o-nitrobenzyl@UCNP nanocapsules using the distillation-precipitation polymerization and templating method. Poly o-nitrobenzyl@UCNP nanocapsules with a robust yolk-shell structure exhibited near-infrared (NIR) light-/pH-responsive properties. When the nanocapsules were exposed to 980 nm NIR irradiation, the loaded drug was efficiently released by altering the shell of the nanocapsules. The photodegradation kinetics of the poly o-nitrobenzyl@UCNP nanocapsules were studied. The anticancer drug, doxorubicin hydrochloride (DOX), was loaded at pH 8.0 with a loading efficiency of 13.2 wt %. The Baker-Lonsdale model was used to determine the diffusion coefficients under different release conditions to facilitate the design of dual-responsive drug release devices or systems. Additionally, cytotoxicity studies showed that the drug release of DOX could be efficiently triggered by NIR to kill cancer cells in a controlled manner.