Advances in the Design of Functional Cellulose Based Nanopesticide Delivery Systems.

The advancement of science and technology, coupled with the growing environmental consciousness among individuals, has led to a shift in pesticide development from traditional methods characterized by inefficiency and misuse toward a more sustainable and eco-friendly approach. Cellulose, as the most abundant natural renewable resource, has opened up a new avenue in the field of biobased drug carriers by developing cellulose-based drug delivery systems. These systems offer unique advantages in terms of deposition rate enhancement, modification facilitation, and environmental impact reduction when designing nanopesticides. Consequently, their application in the field of nanoscale pesticides has gained widespread recognition. The present study provides a comprehensive review of cellulose modification methods, carrier types for cellulose-based nanopesticides delivery systems (CPDS), and various stimulus-response factors influencing pesticide release. Additionally, the main challenges in the design and application of CPDS are summarized, highlighting the immense potential of cellulose-based materials in the field of nanopesticides.

Development and validation of a machine learning-based postoperative prognostic model for plasma cell neoplasia with spinal lesions as initial clinical manifestations: a single-center cohort study.

BACKGROUND: Spinal multiple myeloma (MM) and solitary plasmacytoma of bone (SPB), both plasma cell neoplasms, greatly affect patients' quality of life due to spinal involvement. Accurate prediction of surgical outcomes is crucial for personalized patient care, but systematic treatment guidelines and predictive models are lacking. OBJECTIVE: This study aimed to develop and validate a machine learning (ML)-based model to predict postoperative outcomes and identify prognostic factors for patients with spinal MM and SPB. METHODS: A retrospective analysis was conducted on patients diagnosed with MM or SPB from 2011 to 2015, followed by prospective data collection from 2016 to 2017. Patient demographics, tumor characteristics, clinical treatments, and laboratory results were analyzed as input features. Four types of ML algorithms were employed for model development. The performance was assessed using discrimination and calibration measures, and the Shapley Additive exPlanations (SHAP) method was applied for model interpretation. RESULTS: A total of 169 patients were included, with 119 for model training and 50 for validation. The Gaussian Naïve Bayes (GNB) model exhibited superior predictive accuracy and stability. Prospective validation on the 50 patients revealed an area under the curve (AUC) of 0.863, effectively distinguishing between 5-year survivors and non-survivors. Key prognostic factors identified included International Staging System (ISS) stage, Durie-Salmon (DS) stage, targeted therapy, and age. CONCLUSIONS: The GNB model has the best performance and high reliability in predicting postoperative outcomes. Variables such as ISS stage and DS stage were significant in influencing patient prognosis. This study enhances the ability to identify patients at risk of poor outcomes, thereby aiding clinical decision-making.

Mesenchymal stem cell-derived exosomes as a new drug carrier for the treatment of spinal cord injury: A review.

Spinal cord injury (SCI) is a devastating traumatic disease seriously impairing the quality of life in patients. Expectations to allow the hopeless central nervous system to repair itself after injury are unfeasible. Developing new approaches to regenerate the central nervous system is still the priority. Exosomes derived from mesenchymal stem cells (MSC-Exo) have been proven to robustly quench the inflammatory response or oxidative stress and curb neuronal apoptosis and autophagy following SCI, which are the key processes to rescue damaged spinal cord neurons and restore their functions. Nonetheless, MSC-Exo in SCI received scant attention. In this review, we reviewed our previous work and other studies to summarize the roles of MSC-Exo in SCI and its underlying mechanisms. Furthermore, we also focus on the application of exosomes as drug carrier in SCI. In particular, it combs the advantages of exosomes as a drug carrier for SCI, imaging advantages, drug types, loading methods, etc., which provides the latest progress for exosomes in the treatment of SCI, especially drug carrier.

High deposition and precise stimulus-response release performance of lignin-coated dendritic mesoporous organosilica nanoparticles for efficient pesticide utilization.

The inefficient and improper use of conventional pesticides has prompted the development of targeted and cost-effective pesticide delivery systems, which aim to optimize the efficient utilization of pesticides while minimizing environmental pollution in surrounding areas. In this paper, a dual-stimuli-responsive pesticide slow-release nanopesticide system (NES@DMONs@LGN) was designed in this study, utilizing mesoporous silica (DMONs) as a nanocarrier and lignin (LGN) as a capping agent to encapsulate the pesticide molecules within DMONs. This system enables intelligent release of pesticide molecules while preventing environmental pollution caused by leakage. Additionally, NES@DMONs@LGN exhibit excellent specific loading efficiency. The abundant hydrophilic functional groups in the lignin layer on the surface of NES@DMONs@LGN can establish hydrogen bonds with advanced fatty acids and fatty alcohols present in the waxy epidermis of plants, thereby significantly enhancing carrier wettability and adhesion. Typically, phytophagous lepidopteran pests have an alkaline midgut and possess lignin-degrading enzymes. The NES@DMONs@LGN developed in this study are capable of rapid release under high temperature and alkaline conditions. Therefore, the precise release of pesticide molecules in the target pests can be achieved, thus increasing the actual utilization rate of pesticides. The experimental results demonstrated that NES@DMONs@LGN effectively prevented photodegradation of the active ingredient after 48 h of UV irradiation, resulting in a 3.7-fold improvement in photostability and providing robust UV protection. By encapsulating pesticide molecules with nanocarriers, the release of pesticides in non-targeted environments can be prevented, thereby significantly reducing toxicity to zebrafish. Thus, this study provides a promising solution for sustainable greening of agriculture.

ε-Poly-l-lysine-hydroxyphenyl propionic acid/IL-4 composite hydrogels with inflammation regulation and antibacterial activity for improving integration stability of soft tissues and orthopedic implants.

The failure of orthopedic implants is usually caused by inflammation, poor tissue integration, and infection, which can lead to pain, limited mobility, dysfunction of patients. This may require additional surgical interventions, such as removal, replacement, or repair of implants, as well as related treatment measures such as antibiotic therapy, physical therapy. Here, an injectable hydrogel carrier was developed for the steady release of inflammatory regulators to reduce the surface tissue inflammatory response of orthopedic implants and induce soft tissue regeneration, ultimately achieving the promotion of implants stability. The hydrogels carrier was prepared by hydroxyphenyl propionic acid-modified ε-Poly-l-lysine (EPA), hydrogen peroxide and horseradish peroxidase, which showed antibacterial bioactive and stable factor release ability. Due to the introduction of IL-4, EPA@IL-4 hydrogels showed good inflammatory regulation. EPA@IL-4 hydrogels regulated the differentiation of macrophages into M2 in inflammatory environment in vitro, and promoted endothelial cells to show a more obvious trend of tube formation. The composite hydrogels reduced the inflammation on the surface of the implants in vivo, induced local endothelial cell angiogenesis, and had more collagen deposition and new granulation tissue. Therefore, EPA hydrogels based on IL-4 release are promising candidates for promoting of implants surface anti-inflammatory, soft tissue regeneration, and anti-infection.

Improved secretory expression and characterization of thermostable xylanase and ß-xylosidase from Pseudothermotoga thermarum and their application in synergistic degradation of lignocellulose.

Xylanase and ß-xylosidase are the key enzymes for hemicellulose hydrolysis. To further improve hydrolysis efficacy, high temperature hydrolysis with thermostable hemicellulases showed promise. In this study, thermostable xylanase (Xyn) and ß-xylosidase (XynB) genes from Pseudothermotoga thermarum were cloned and secretory expressed in Bacillu subtilis. Compared with Escherichia coli expression host, B. subtilis resulted in a 1.5 time increase of enzymatic activity for both recombinant enzymes. The optimal temperature and pH were 95°C and 6.5 for Xyn, and 95°C and 6.0 for XynB. Thermostability of both recombinant enzymes was observed between the temperature range of 75-85°C. Molecular docking analysis through AutoDock showed the involvement of Glu525, Asn526, Trp774 and Arg784 in Xyn-ligand interaction, and Val237, Lys238, Val761 and Asn76 in XynB-ligand interaction, respectively. The recombinant Xyn and XynB exhibited synergistic hydrolysis of beechwood xylan and pretreated lignocellulose, where Xyn and XynB pre-hydrolysis achieved a better improvement of pretreated lignocellulose hydrolysis by commercial cellulase. The observed stability of the enzymes at high temperature and the synergistic effect on lignocellulosic substrates suggested possible application of these enzymes in the field of saccharification process.

Targeting CDK4/6 in glioblastoma via in situ injection of a cellulose-based hydrogel.

Despite aggressive treatments, including surgery, chemotherapy and radiotherapy, the prognosis of glioblastoma (GBM) remains poor, and tumor recurrence is inevitable. The FDA-approved CDK4/6 inhibitor palbociclib (PB) showed interesting anti-GBM effects, but its brain penetration is limited by the blood-brain barrier. The aim of this project is to find whether the cellulose-based hydrogel via in situ injection could provide an alternative route to PB brain delivery and generate sufficient drug exposure in orthotopic GBM. In brief, PB was encapsulated in a cellulose nanocrystal network structure crosslinked by polydopamine via divalent Cu2+ and hexadecylamine. The formed hydrogel (PB@PH/Cu-CNCs) exhibited sustained drug retention and acid-responsive network de-polymerization for controlled release in vivo. Specifically, the released Cu2+ catalyzed a Fenton-like reaction to generate reactive oxygen species (ROS), which was further enhanced by PB, and consequently, irreversible senescence and apoptosis were induced in GBM cells. Finally, PB@PH/Cu-CNCs demonstrated a more potent anti-GBM effect than those treated with free PB or PH/Cu-CNCs (drug-free hydrogel) in cultured cells or in an orthotopic glioma model. These results prove that the injection of the PB-loaded hydrogel in situ is an effective strategy to deliver the CDK4/6 inhibitor into the brain and its anti-GBM effect can be further enhanced by combining Cu2+-mediated Fenton-like reaction.

Separation of flavonoids with significant biological activity from Acacia mearnsii leaves.

Acacia mearnsii leaves, which are a rich source of flavonoids, were used to separate and purify myricitrin (W3) and myricetin-3-O-glucoside (W1). Further, the antioxidant and hypoglycemic activities of the two purified flavonoids were evaluated. The flavonoids were separated using solvent partition, macroporous adsorbent resin column, and Sephadex column chromatography, and purified using preparative reverse-phase high-performance liquid chromatography (HPLC). The purified flavonoids were characterized using HPLC, mass spectrometry, and nuclear magnetic resonance methods. A high yield (7.3 mg g-1 of crude extract) of W3 was obtained, with a high purity of 98.4%. Furthermore, the purity of W1 was over 95%. W1 and W3 showed strong antioxidant activity and significantly inhibited α-glucosidase. W3 also demonstrated substantial α-amylase inhibitory capacity. This study indicated that A. mearnsii leaves, which are discarded in significant amounts, can be used as a source of myricitrin, thus providing more adequate material for the production of antioxidants and type II diabetes inhibitors. Hence, A. mearnsii leaves have the potential to create great market economic value and environmental benefits.

Nanocellulose-based drug carriers: Functional design, controllable synthesis, and therapeutic applications.

With rising living standards and environmental awareness, materials-oriented chemical engineering has increasingly transitioned from traditional rough models to more resource-saving and eco-friendly models, providing an avenue for bio-based materials in the drug carrier field. Because of its excellent physical and chemical properties, including high specific surface area, abundant accessible hydroxyl groups, biocompatibility, and degradability, nanocellulose (NC) is an emerging bio-based material that has been widely exploited as biomedical materials. The modification techniques of NC, as well as advancements in the design and applications of drug carriers, were primarily discussed in this study. First, the NC modification methods are described; second, the applications of NC and its derivatives as drug carriers are summarized, focusing on NC-based carrier models, types of loaded therapeutic agents, and controlled release stimulators; and finally, the current challenges of NC in the drug carrier field and the directions of future research are also discussed.

Surgical management and outcome of Extra-adrenal myelolipomas at unusual locations: A report of 11 cases in a single center.

Purpose: Extra-adrenal myelolipomas (EAMs) are rare benign tumors composed of both mature adipose and hematopoietic tissues with unclear etiology. There have been only sporadic case reports about the clinical characteristics and management of EAMs. Here we present our experience and practice in the clinical diagnosis and treatment of 11 consecutive patients with EAMs. Method: We retrospectively reviewed 11 consecutive patients, who received surgeries in our department and were confirmed as having EAMs by postoperative histopathology from April 2016 to December 2021. Clinical information and follow-up data of all patients were collected and analyzed afterwards. Results: Of the 11 EAM patients (7 male and 4 female) with a mean age of 47.6 years, 3 were asymptomatic and 8 were symptomatic with a mean symptom duration of 6.07 months. EAMs were found in the thoracic spine in 4 cases, paravertebral mediastinal regions in 3 cases, ilium in 2 cases, humerus in 1 case, and rib in 1 case. All patients were initially misdiagnosed as other tumors by radiologists. All 11 patients received gross total excision or curettage with a mean intraoperative blood loss of 781.82 ± 1143.3 ml and a mean operation duration of 180.91 ± 98.41 min. Patients' Frankel scores and Karnofsky Performance Status score were improved or at least preserved postoperatively. No significant complications occurred postoperatively. All the 11 patients survived, and no local recurrence or distant metastasis occurred during the mean follow-up period of 42.0 months. Conclusion: The surgical outcome and prognosis of EAMs are excellent and surgery can serve as the method of radical treatment.

Toxic reactive oxygen species enhanced chemodynamic therapy by copper metal-nanocellulose based nanocatalysts.

When compared with traditional petroleum-based materials, bio-based materials show greater application potential in the field of biomedicine owing to the good biocompatibility, in specifical, the application of natural macromolecular polymers in chemotherapeutics has become a hot topic in anticancer treatment. In this study, cellulose nanocrystals (CNCs) were selected as carriers, and Au nanoparticles (NPs) were directly conjugated on their surface, with the highly reactive Cu2+ ions serving as an ion-ligand bridge, to construct a multifunctional nanocatalyst. These findings suggest that the nanosystem delivers a large amount of highly reactive Cu2+ ions (3.75 wt%) and DOX (7.71 wt%) by the surface loading of cellulose nanocrystals, which greatly improves ROS yield and promotes the application of the Fenton reaction system in cancer therapy.

Small-Molecule-Selective Organosilica Nanoreactors for Copper-Catalyzed Azide-Alkyne Cycloaddition Reactions in Cellular and Living Systems.

We reported the synthesis of a tris(triazolylmethyl)amine (TTA)-bridged organosilane, functioning as Cu(I)-stabilizing ligands, and the installation of this building block into the backbone of mesoporous organosilica nanoparticles (TTASi) by a sol-gel way. Upon coordinating with Cu(I), the mesoporous CuI-TTASi, with a restricted metal active center inside the pore, functions as a molecular-sieve-typed nanoreactor to efficiently perform Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reactions on small-molecule substrates but fails to work on macromolecules larger than the pore diameter. As a proof of concept, we witnessed the advantages of selective nanoreactors in screening protein substrates for small molecules. Also, the robust CuI-TTASi could be implanted into the body of animal models including zebrafish and mice as biorthogonal catalysts without apparent toxicity, extending its utilization in vivo ranging from fluorescent labeling to in situ drug synthesis.

tLyP-1 Peptide Functionalized Human H Chain Ferritin for Targeted Delivery of Paclitaxel.

PURPOSE: The aims of this study were to test the feasibility, targeting specificity and anticancer therapeutic efficacy of CendR motif tLyP-1 functionalized at the N-terminal of ferritin for paclitaxel (PTX) delivery. METHODS: A tumor homing and penetrating peptide tLyP-1 was fused to the N-terminal of human H chain ferritin (HFtn) to generate a dual-targeting nanoparticle delivery system. PTX molecules were encapsulated into the HFtn nanocage using the disassembly/assembly method by adjusting pHs. Cellular uptake was examined by confocal laser scanning microscopy (CLSM) and flow cytometry. The MTT assay was used to test the cytotoxicity of various PTX-loaded NPs against MDA-MB-231 and SMMC-7721 tumor cells. The wound healing and cell migration assays were conducted to assess the inhibitory effect on cell motility and metastasis. The inhibition effect on the SMMC-7721 tumor spheroids was studied and penetration ability was evaluated by CLSM. The antitumor efficacy of PTX-loaded NPs was assessed in MDA-MB-231 breast cancer xenografted in female BALB/c nude mice. RESULTS: Compared with HFtn-PTX, in vitro studies demonstrated that the tLyP-1-HFtn-PTX displayed enhanced intracellular delivery and better cytotoxicity and anti-invasion ability against both SMMC-7721 and MDA-MB-231 cells. The better penetrability and growth inhibitory effect on SMMC-7721 tumor spheroids were also testified. In vivo distribution and imaging demonstrated that the tLyP-1-HFtn-PTX NPs were selectively accumulated and penetrated at the tumor regions. Verified by the breast cancer cells model in BABL/c nude mice, tLyP-1-HFtn-PTX displayed higher in vivo therapeutic efficacy with lower systemic toxicity. CONCLUSION: Ferritin decorated with tumor-homing penetration peptide tLyP-1 at the N terminal could deliver PTX specifically inside the cell via receptor-mediated endocytosis with better efficacy. The peptide tLyP-1 which is supposed to work only at the C terminus showed enhanced tumor tissue penetration and antitumor efficacy, demonstrating that it also worked at the N-terminal of HFtn.

A biocompatible and pH-responsive nanohydrogel based on cellulose nanocrystal for enhanced toxic reactive oxygen species generation.

Traditional therapeutic regimens are currently far from satisfactory, and the integration of biocompatible carbohydrate polymers and nanotechnologies with conventional therapeutics has become a focus of research in cancer therapy. Herein, A novel biocompatible and pH-responsive nanohydrogel composed of two functional polymeric chains was developed from cellulose nanocrystals (CNCs) and 5-aminolevulinic acid (ALA), or dopamine (DPA). The biological molecules PDA and ALA were respectively conjugated to CNC through the coordination of iron ions to form two functional polymeric chains (PDA/Fe@CNC and ALA/Fe@CNC). The PDA/Fe@CNC chain increased the adhesion of the nanohydrogels to cells, while the ALA/Fe@CNC chain significantly increased reactive oxygen species (ROS) production. Furthermore, PTX molecules loaded into the nanohydrogels combined with ROS to efficiently kill tumor cells. The nanohydrogels displayed excellent cell affinity, high ROS yield (8.0-fold greater than that in control), and strong cytotoxicity (2.7 % of cell viability). The present study highlights the great potential of biocompatible natural polysaccharide-based materials for biomedical applications, and provides a new strategy for reducing the toxicity and side effects associated with traditional chemotherapy, demonstrating a novel antitumor treatment paradigm with high-efficiency but with only minor side effects.

One-for-all intelligent core-shell nanoparticles for tumor-specific photothermal-chemodynamic synergistic therapy.

Reasonable management of the one-for-all nanoplatform can facilitate improved cancer therapy. Here, the metal-organic frameworks (MOFs) based on iron(iii) carboxylate material (MIL-101-NH2) were in situ decorated on stabilized polydopamine nanoparticles (PDANPs), which subsequently loaded glucose oxidase (GOx) via hyaluronic acid (HA) coating to structure the one-for-all intelligent core-shell nanoparticles (HG-MIL@PDANPs). Because of the inner PDANPs, the HG-MIL@PDANPs could realize near-infrared (NIR)-controllable site-specific photothermal therapy (PTT). Additionally, the core-shell nanoparticles exhibited a pH-triggered and NIR-reinforced release of Fe3+ and GOx owing to the controllable degradation of the outer shell. Hydroxyl radicals (˙OH) were produced for chemodynamic therapy (CDT) employing the Fe2+-driven Fenton reaction, which could be greatly promoted by Fe3+-involved glutathione (GSH) depletion and GOx-catalyzed acidity recovery and H2O2 self-sufficiency. Moreover, the HA ligand could enhance the tumor accumulation of the HG-MIL@PDANPs through the long blood circulation time and CD44-targeted cell recognition. The ingenious integration of PTT and CDT in one fully equipped system presented excellent synergistic antitumor efficiency in vitro and in vivo with favorable biosafety. The one-for-all intelligent core-shell nanoparticles with CD44 targeting provide a new avenue for engineering on-demand tumor-specific therapy.

Smart Porous Core-Shell Cuprous Oxide Nanocatalyst with High Biocompatibility for Acid-Triggered Chemo/Chemodynamic Synergistic Therapy.

The rational integration of chemotherapy and hydroxyl radical (·OH)-mediated chemodynamic therapy (CDT) holds great potential for cancer treatment. Herein, a smart biocompatible nanocatalyst based on porous core-shell cuprous oxide nanocrystals (Cu2 O-PEG (polyethylene glycol) NCs) is reported for acid-triggered chemo/chemodynamic synergistic therapy. The in situ formed high density of hydrophilic PEG outside greatly improves the stability and compatibility of NCs. The porosity of Cu2 O-PEG NCs shows the admirable capacity of doxorubicin (DOX) loading (DOX@Cu2 O-PEG NCs) and delivery. Excitingly, Cu (Cu+/2+ ) and DOX can be controllably released from DOX@Cu2 O-PEG NCs in a pH-responsive approach. The released Cu+ exerts Fenton-like catalytic activity to generate toxic ·OH from intracellular overexpressed hydrogen peroxide (H2 O2 ) for CDT via reactive oxygen species (ROS)-involved oxidative damage. Exactly, DOX can not only induce cell death for chemotherapy but also enhance CDT by self-supplying endogenous H2 O2 . After the intravenous injection, Cu2 O-PEG NCs can effectively accumulate in tumor region via passive targeting improved by external high-density PEG shell. Additionally, the effect of boosted CDT combined with chemotherapy presents excellent in vivo antitumor ability without causing distinct systemic toxicity. It is believed that this smart nanocatalyst responding to the acidity provides a novel paradigm for site-specific cancer synergetic therapy.

A pH-activated autocatalytic nanoreactor for self-boosting Fenton-like chemodynamic therapy.

The emergence of hydroxyl radical (˙OH)-mediated chemodynamic therapy (CDT) by the Fenton or Fenton-like reaction holds great potential for improving anticancer efficacy. Herein, an activatable autocatalytic nanoreactor (HT@GOx-DMONs) was developed for self-boosting Fenton-like CDT via decorating Cu2+-based metal-organic frameworks (MOFs) on glucose oxidase (GOx)-loaded dendritic mesoporous organosilica nanoparticles (DMONs) for the first time. The obtained nanoreactor could prevent the premature leakage of Cu2+ and GOx in neutral physiological environments conducted by the gatekeeper of growing carboxylate MOF (HKUST-1), but the explosive release of agents was realized due to the activated degradation of external HKUST-1 in acidic condition of endo/lysosomes, which thereby endowed this nanoreactor with the performance of pH-triggered ˙OH generation driven by Cu+-mediated autocatalytic Fenton-like reaction. Excitingly, Cu2+-induced glutathione (GSH) depletion and GOx-catalyzed H2O2 self-sufficiency unlocked by acid dramatically enhanced ˙OH generation. As expected, the effect of self-amplified CDT based on Cu2+-containing HT@GOx-DMONs presented wonderful in vitro toxicity and in vivo antitumor ability without leading to significant side-effects. The resulting nanoreactor with GSH consumption and H2O2 self-supply activated by acid may provide a promising paradigm for on-demand CDT.

Dendritic Mesoporous Organosilica Nanoparticles: A pH-Triggered Autocatalytic Fenton Reaction System with Self-supplied H2O2 for Generation of High Levels of Reactive Oxygen Species.

Dendritic mesoporous silica nanoparticles represent a new biomedical application platform due to their special central radial pore structure for the loading of drugs and functional modification. Herein, we report functionalized dendritic mesoporous organosilica nanoparticles (DMONs), a pH-triggered Fenton reaction generator (TA/Fe@GOD@DMONs), incorporating natural glucose oxidase (GOD) in the DMONs with tannic acid (TA) grafted using Fe3+ on the surface, that have been designed and constructed for efficient tumor ablation with self-supplied H2O2 and accelerated conversion of Fe3+/Fe2+ by TA. In view of the deficiency of endogenous H2O2, the self-supply through the TA/Fe@GOD@DMONs platform represented a high-yielding source of peroxygen. Furthermore, the production of Fe2+ induced by TA greatly improved the efficiency of the Fenton reaction resulting in significant tumor inhibition. This new design represents as novel paradigm for the development of autocatalytic Fenton nanosystems for effective treatment of tumors.

A CD44-targeted Cu(ii) delivery 2D nanoplatform for sensitized disulfiram chemotherapy to triple-negative breast cancer.

Recent studies have suggested that the anticancer activity of disulfiram (DSF, an FDA-approved alcohol-abuse drug) is Cu-dependent. Low system toxicity and explicit pharmacokinetic characteristics of DSF necessitate safe and effective Cu supplementation in local lesion for further applications. Herein, we presented a new conceptual 'nanosized coordination transport' strategy of Cu(ii) that was realized in porphyrin-based metal-organic frameworks, Sm-TCPP, with strong binding ability to Cu(ii) due to their coordination interactions. Sm-TCPP(Cu) was coated by hyaluronic acid (HA) that termed by Sm-TCPP(Cu)@HA, acting as 'beneficial horse' to target the tumor-localized HA receptor (CD44), thus liberating Cu(ii) ions in cellular overexpressed reductants. The CD44-mediated Cu(ii) accumulation efficiency of Sm-TCPP(Cu)@HA was benchmarked in vitro and vivo against the free TCPP (Cu) via ICP-MS analysis. More importantly, the sensitization effects of Sm-TCPP(Cu)@HA on the anticancer activity of DSF were demonstrated in vivo and in vitro. This study offered a new class of targeted Cu supplements to sensitize DSF for the effective treatment of cancer and established a versatile methodology for constructing a safe and specific delivery of metal ions within living organisms.

A novel versatile yolk-shell nanosystem based on NIR-elevated drug release and GSH depletion-enhanced Fenton-like reaction for synergistic cancer therapy.

In this study, a versatile doxorubicin (DOX)-loaded yolk-shell nano-particles (HMCMD) assembled with manganese dioxide (MnO2) as the core and copper sulfide (HMCuS) as the mesoporous (∼ 6.4 nm) shell, was designed and synthesized. The resulting HMCMD possess excellent photothermal conversion efficiency. The DOX release from the yolk-shell nanoparticles could be promoted by laser irradiation, which increased the chemotherapy of DOX. Meanwhile, Mn2+ could be released from the HMCMD through a redox reaction between MnO2 and abundant glutathione (GSH) in tumor cells. The released Mn2+ could promote the decomposition of the intracellular hydrogen peroxide (H2O2) by Fenton-like reaction to generate the highly toxic hydroxyl radicals (·OH), thus exhibiting the effective chemodynamic therapy (CDT). Additionally, the efficiency of Mn2+-mediated CDT could be effectively enhanced by NIR irradiation. Further modification of polyethylene glycol (PEG) would improve the water solubility of the HMCMD to promote the uptake by MCF-7 cells. Hence, the HMCMD with synergistic effects of chemotherapy and chemodynamic/photothermal therapy would provide an alternative strategy in antitumor research.