Drug-loading System Research Articles

Improved Antiglioblastoma Activity and BBB Permeability by Conjugation of Paclitaxel to a Cell-Penetrative MMP-2-Cleavable Peptide.

In order to solve the problems of receptor promiscuity and poor blood‐brain barrier (BBB) penetration in the treatment of glioblastomas (GBM), a novel dual‐functional nanocomplex drug delivery system is developed based on the strategy of peptide‐drug conjugates. In this study, SynB3‐PVGLIG‐PTX is designed and screened out by matrix metalloproteinase‐2 (MMP‐2), to which it exhibits the best affinity. The MMP‐2‐sensitive peptide (PVGLIG) and a cell‐penetration peptide (SynB3) are combined to form a dual‐functional peptide. Moreover, as a drug‐peptide nanocomplex, SynB3‐PVGLIG‐PTX exhibited a high potential to form an aggregation with good solubility that can release paclitaxel (PTX) through the cleavage of MMP‐2. From a functional perspective, it is found that SynB3‐PVGLIG‐PTX can specifically inhibit the proliferation, migration, and invasion of GBM cells in vitro in the presence of MMP‐2, in contrast to that observed in MMP‐2 siRNA transfected cells. Further investigation in vivo shows that SynB3‐PVGLIG‐PTX easily enters the brain of U87MG xenograft nude mice and can generate a better suppressive effect on GBM through a controlled release of PTX from SynB3‐PVGLIG‐PTX compared with PTX and temozolomide. Thus, it is proposed that SynB3‐PVGLIG‐PTX can be used as a novel drug‐loading delivery system to treat GBM due to its specificity and BBB permeability.

Chitosan-hydrophobic alginate nanocomposites stabilized pH-triggered Pickering emulsion for drug controlled-release

Alginate or chitosan microparticles as drug loading system performed pH-responsiveness and biocompatibility, yet with the burst-release and limited encapsulation. In order to improve the performance, herein, Pickering emulsion of chitosan-hydrophobic alginate nanocomposite (HSA-CS NCs) as the bio-stabilizer, was proposed as the drug-loading vehicle. Integrating the merits of HSA-CS and Pickering emulsion, such drug carrier of emulsion performed pH-response and biocompatibility from HSA-CS, and high loading capacity and rigid layer from Pickering emulsion, so as for the manipulated release behavior. With thorough investigation, via the various pH-response of HSA-CS nanocomposite in the continuous simulated gastrointestinal fluid, Pickering emulsion gradually released the loading drug (ibuprofen) out, performing the pH-triggered controlled-release behavior. Ibuprofen-loaded Pickering emulsions (30 mg/mL) released nearly none in SGF for 3 h, whereas in SIF, performed constant release in initial 5 h and continuous-release of 88.37% ibuprofen in 24 h with no drug-burst and high loading capacity, promisingly as the pH-responsive vehicle for drug delivery in oral route.

8-Hydroxyquinoline functionalized covalent organic framework as a pH sensitive carrier for drug delivery.

A porous 8-hydroxyquinoline functionalized organic covalent framework (named COF-HQ) was synthesized. The as-prepared COF-HQ showed stable crystal structure, suitable pore size, excellent dispersibility in physiological solution and pH sensitivity, which would be employed as a potential nanocarrier for drug transport and controlled release. The drug loading experiment with 5-Fluorouracil (5-FU) as the model molecule proved that the drug loading capacity of COF-HQ was significantly improved due to the introduction of quinoline groups. The drug release profiles of 5-FU from 5-FU loaded COF-HQ (termed 5-FU@COF-HQ) under different pH showed that its release was controlled by pH owing to the pH sensitivity of conjugated nitrogen atoms from quinoline groups and CN. The in vitro hemolysis and in vivo biocompatibility experiments further verified the good biocompatibility of COF-HQ. Importantly, 5-FU@COF-HQ-treated B16F10 cell-induced tumor models showed that 5-FU@COF-HQ displayed enhanced anti-tumor efficacy than other groups. These results suggested that the drug-loading COF-HQ delivery system showed the potential for effective cancer therapy with advantages of high drug loading, good biocompatibility and the pH-sensitive release of the tumor microenvironment. Overall, our research provided a new functionalized COF-HQ drug delivery system, which further expanded the application of COFs as carriers in the field of cancer treatment.

Single-Wall Carbon Nanotube Uptake Based on Energy-Dependence and Metastatic Potential of Epithelial Cells Motivates Carrier Delivery of Drugs for Targeting Cancer

Cancer cells have altered metabolic activity that can be appropriated for delivery of drugs. Rapidly proliferating cancer cells internalize a high amount of protein-dispersed single-wall carbon nanotubes (SWCNTs) with increased endocytosis from deprivation of metabolic fuels, overexpression and increased recycling of membrane receptors, and mechanosensitivity. Differential uptake of protein-dispersed SWCNTs in various cell types have been reported previously, demonstrating that SWCNT uptake highly depends on uptake pathway and cell metabolism. However, there is still gap in understanding how metastatic potential and cell metabolism can differentiate SWCNT uptake and delivery of drugs in a type of cells. In this work, we present uptake and efficacy of SWCNTs/drug/protein complexes in three different epithelial cell lines, NRK-52E, HeLa, and Hs 578T, that present different metabolic levels from their metastatic potentials. We first create SWCNTs/drug/protein complexes with doxorubicin, a common model cancer drug, and bovine serum albumin (BSA), a model protein that has been extensively studied with SWCNT, using a previously developed unique drug loading system using stepwise assembly on SWCNT networks. The result presented that the cells takes up SWCNTs differently in accordance to their metabolic activity, where Hs 578T cells, with the highest metastatic potential and metabolism, take up ~ 10× more nanotubes compared to an epithelial monolayer of NRK-52E cells. Extent of reduction in cell viability from the delivered drugs were in line with the amount of SWCNT uptake. Our work provides further understanding of differential uptake of protein-dispersed SWCNTs with respect to metabolism and energy requirement of the cells. This suggests that protein-dispersed SWCNTs could preferentially target and deliver drugs to cancer cells in a local area with a combination of normal epithelial cells and cancerous cells.

Novel pH-Sensitive Hydrogel Beads Based on Carrageenan and Fish Scale Collagen for Allopurinol Drug Delivery

In this work, pH-sensitive hydrogel beads based on fish scale collagen and carrageenan were used as a novel allopurinol drug loading system to improve the bioavailability of allopurinol, which is used to treat gout and high levels of uric acid in the human body. The effectiveness of the carrageenan/collagen/allopurinol hydrogel beads in improving the physical properties of allopurinol and the ability for drug release control in different simulated body fluids were evaluated by infrared (IR) spectroscopy, field emission scanning electron microscopy (FESEM), differential scanning calorimetry (DSC), dynamic light scattering (DLS) and Ultraviolet–Vis (UV–Vis) spectroscopy. In addition, the ability of hydrogen bond formation between allopurinol, carrageenan and collagen was calculated theoretically based on the B3LYP/6-31+g(d)//B3LYP/6-311++g(d,p) level of theory. Both the theoretical and experimental results proved that the hydrogen bonds of the functional groups in allopurinol with the functional groups in carrageenan and fish scale collagen contributed to the enhancement of drug release control as well as to the bioavailability of allopurinol loaded into the carrageenan/collagen hydrogel beads. The dissolution of carrageenan/collagen/allopurinol hydrogel beads in different simulated body fluids increased by 1.6 to 6.7 times compared to that of crystalline allopurinol.

In situ inflammatory-regulated drug-loaded hydrogels for promoting pelvic floor repair

Biomedical hydrogel has been widely used as regenerative biomaterials, however, an immune inflammatory response of hydrogel constantly crops up in body due to crosslinking agent, external stimulus or small molecule residues. Here we present a strategy to treat pelvic organ prolapse (POP) by combining both anti-inflammatory and promote tissue regeneration, using drug-loaded hydrogel to reconstruct the pelvic floor and minimize multiple inflammations. Photo-crosslinked gelatin hydrogel (GelMA) loaded with Puerarin (Pue) regulate inflammation by inhibiting the aggregation of neutrophils and eosinophils, simultaneously intervene the matrix regenerating/remodeling via TGF-β/MMPs pathway to repair the fascia of pelvic floor in rabbit models (POP model). The assessment of inflammatory cytokines expression (IL-3, IL-6, TNF-α, TGF-β1) in human uterus fibroblasts (HUVs), and extracellular matrix (ECM) related factors (COL-1, COL-3, MMP2, MMP9) was performed in rabbit. Immune microenvironment was analyzed by immunohistochemistry in rabbit samples. Pue-loaded GelMA (Pue@GelMA) down regulate inflammatory cytokines (IL-3 and IL-6) and matrix metalloproteinase 2/9 (MMP 2/9), and up regulate 1/3 type collagen (COL-1/3) in vitro. In this study, Pue@GelMA was able to regulate immune microenvironment through restricting the aggregation of neutrophils and eosinophils and remodel the distribution of ECM collagen in vivo. In the POP model, Pue@GelMA can effectively inhibits the inflammatory response caused by material implanted and promote fascia regenerate. This Hydrogel drug loading system was considered as an safe and effective method to treat POP without persistent complications, and it can also be applied to other prolapse diseases (e.g., intestinal hernia) or complex diseases treatment.

Preparation and anti-cancer activity of transferrin/folic acid double-targeted graphene oxide drug delivery system.

In this study, a transferrin/folic acid double-targeting graphene oxide drug delivery system loaded with doxorubicin was designed. Graphene oxide was prepared by ultrasound improved Hummers method and was modified with Pluronic F68, folic acid, and transferrin to decrease its toxicity and to allow dual-targeting. The results show that the double target drug delivery system (TFGP*DOX) has good and controllable drug delivery performance with no toxicity. Moreover, TFGP*DOX has a better inhibitory effect on SMMC-7721 cells than does a single target drug delivery system (FGP*DOX). The results of drug release analysis and cell inhibition studies showed that TFGP*DOX has a good sustained release function that can reduce the drug release rate in blood circulation over time and improve the local drug concentration in or near a targeted tumor. Therefore, the drug loading system (TFGP*DOX) has potential application value in the treatment of hepatocellular carcinoma.

Graphene-based nanomaterials combined with early exercise rehabilitation training in the treatment of patients with infectious bone defects

With the rapid development of industry and transportation, the incidence of open fractures caused by high-energy injuries has increased year by year, and bone infections are prone to occur after open fractures. According to the needs for the treatment of open fracture infections and bone defects, graphene in carbon nanomaterials has many advantages as bone graft materials. The purpose of this study was to make use of the unique physical and chemical properties of carbon nanomaterials to prepare a three-dimensional composite scaffold with good bone properties and some antibacterial properties, and carry antibiotics for the treatment of infection and bone defect after open fractures. The results show that the prepared reduced graphene oxide (RGO)-nHA composite scaffold has an interconnected three-dimensional porous structure, and the bone formation performance is enhanced when nHA is incorporated, which can promote cell growth and bone regeneration; vancomycin is loaded on this composite scaffold later, due to the bonding with graphene, the drug can be released relatively quickly in the initial stage, and then the drug is released slowly. The combination of the drug's sustained release characteristics and the inherent antibacterial activity of graphene can ensure rapid treatment of infections, and provide lasting inhibition of bacteria. In vivo experiments have also shown that the drug-loading system can effectively treat infectious bone defects.

Preparation of Lysozyme-Responsive Nanodiamond Drug-Loading System and the Effect on HepG2 Cells

Preparation of Lysozyme-Responsive Nanodiamond Drug-Loading System and the Effect on HepG2 Cells

Construction and in vitro and in vivo evaluation of folic acid-modified nanostructured lipid carriers loaded with paclitaxel and chlorin e6.

Breast cancer remains a major threat to women's health, and the incidence of breast cancer continues to increase each year. Paclitaxel (PTX) is commonly used to treat breast cancer, but shows limited solubility and is associated with major side effects, limiting its clinical applications. Photodynamic therapy (PDT) is a promising treatment for breast cancer but is limited by the poor solubility of photosensitizers and difficulties in targeting and enriching the tumor tissue with photosensitizers. Here, we prepared a new nanocarrier system using nanostructured lipid carriers (PTX@FA-NLC-PEG-Ce6) harboring PTX, chlorin e6 (Ce6), and folic acid-targeted head to overcome the limitations of PTX and Ce6 in hydrophobicity and increase the target efficiency of chemotherapy drugs and photosensitizers at the tumor. The results showed that the drug-loading system met the requirements for intravenous injection, had tumor targeting ability, and could be easily taken up by MDA-MB-231 cells. Moreover, Ce6 could be dissociated from the surface of the drug-loading system and evenly distributed in cells after a period of time when the nanostructured lipid carriers had entered lysosomes through endocytosis. Additionally, reactive oxygen species were then produced to induce PDT at a specific wavelength of illumination. In vitro pharmacodynamic experiments showed that combined PDT and chemotherapy had synergistic effects (combination index: 0.647). Furthermore, pharmacodynamic experiments in nude mice showed that the drug-loading system had ideal antitumor effects without obvious side effects. Thus, PTX@FA-NLC-PEG-Ce6 may have applications as a promising drug-loading system for PDT combined with chemotherapy in patients with breast cancer.

Reductive response and RGD targeting nano-graphene oxide drug delivery system

Cancer cell therapy using redox response and targeted drug delivery systems can increase therapeutic effects of anti-cancer therapy. Here, we report a redox-responsive drug carrier based on nanoscale Graphene Oxide (GO) loaded with Doxorubicin (DOX). In this drug carrier demonstration, we utilized Arginine-glycine-aspartic acid (RGD) peptide, aminated polyethylene glycol (6ARM-PEG-NH2, PEG-NH2) to functionalize the GO. To integrate the carrier with a redox responsive property, we utilized disulfide linkages (3,3′-dithiodipropionic acid (DTPA)), which can be cleaved by glutathione (GSH) combined with the PEG-NH2. Our results show that DOX is rapidly released in a pH = 5.50 PBS solution with GSH concentration of 10 mM. The drug-loading system (RGD-GO-PEG-S-S-DOX) combined with photo-thermotherapy possesses good inhibition activity of Hep-G2 cells at a relatively low concentration. When the concentration of RGD-GO-PEG-S-S-DOX was 1.56 μg/mL, the inhibition activity of Hep-G2 cells was 78%. Because tumor cells generally exhibit a higher concentration of GSH than normal ones, and tumor blood vessels are distorted and dilated, and the blood flow resistance tends to be large, tumor cells are more sensitive to temperature changes than normal tissues. Thus, drug delivery systems, like the one we studied, have potential applications in a therapeutic strategy for the treatment of liver cancer.

Targeted acetylcholinesterase-responsive drug carriers with long duration of drug action and reduced hepatotoxicity.

PurposeAcetylcholinesterase (AChE) plays a critical role in the transmission of nerve impulse at the cholinergic synapses. Design and synthesis of AChE inhibitors that increase the cholinergic transmission by blocking the degradation of acetylcholine can serve as a strategy for the treatment of AChE-associated disease. Herein, an operational targeted drug delivery platform based on AChE-responsive system has been presented by combining the unique properties of enzyme-controlled mesoporous silica nanoparticles (MSN) with clinical-used AChE inhibitor.MethodsFunctionalized MSNs were synthesized by liquid phase method and characterized by using different analytical methods. The biocompatibility and cytotoxicity of MSNs were determined by hemolysis experiment and MTT assay, respectively. Comparison of AChE activity between drug-loading system and inhibitor was developed with kits and by ELISA method. The efficacy of drug-loaded nanocarriers was investigated in a mouse model.ResultsCompared with AChE inhibitor itself, the inhibition efficiency of this drug delivery system was strongly dependent on the concentration of AChE. Only AChE with high concentration could cause the opening of pores in the MSN, leading to the controlled release of AChE inhibitor in disease condition. Critically, the drug delivery system can not only exhibit long duration of drug action on AChE inhibition but also reduce the hepatotoxicity in vivo.ConclusionIn summary, AChE-responsive drug release systems have been far less explored. Our results would shed lights on the design of enzyme controlled-release multifunctional system for enzyme-associated disease treatment.

Biopeptide Hyperbranched Polyether Assembled from Lactic Acid, Glutamic Acid and Polyethylene Glycol Block Chains for Drug Loading

A drug loading system based on biopeptide hyperbranched polyether (BHPE) had been prepared. The biopeptide hyperbranched polymer (BHP) was composed of trimellitic anhydride, lactic acid and glutamic acid chains. The BHPE was assembled by the BHP and polyethylene glycol 400 (PEG400). The effects of pH, mass ratio of BHP and PEG400 and reaction time on particle size and distribution were studied. When the pH was 7, the mass ratio of BHP and PEG400 was 1:4 and the reaction time was 1.5 h, the BHPE formed the appropriate hollow vesicle structure which the particle size was smaller and particle size distribution was better. Also the sample of BHPE exhibited the excellent performances on swelling and in vitro degradation. The salicylic acid (SA) was used as drug model and the properties of SA-loaded BHPE system were tested by LPSA, UV-Vis and TEM. The SA-loaded BHPE system possessed obvious core-skin structure, and it demonstrated good in vitro released performance.

Preparation of Graphene Nano Drug-Loading System and Its Killing Effect on Human Oral Squamous Cell Carcinoma Cells

Preparation of Graphene Nano Drug-Loading System and Its Killing Effect on Human Oral Squamous Cell Carcinoma Cells

Polymeric Drug Delivery System with Actively Targeted Cell Penetration and Nuclear Targeting for Cancer Therapy.

Targeted tumor cell killing using polymeric micelles with active targeting strategies has been demonstrated to be effectively therapeutic for liver cancers. To implement this strategy, enhancing the cellular uptake of the drug delivery system with targeted anticancer drugs, such as doxorubicin toward nuclear targeting, is of vital importance for increasing drug efficiency and reducing the systemic side effects of encapsulated drugs. In this study, a multifunctional polymeric drug delivery system was designed with actively targeted cell penetration and nuclear targeting for efficient cancer therapy. The nanocarriers were self-assembled from poly(ethylene glycol)-block-poly(ε-caprolactone), decorated with folic acid (FA-PECL) for active targeting via amide reaction for selective delivery of drugs to tumors. A cell penetration peptide (CPP) was decorated with doxorubicin (DOX), and the conjugate (CPP-DOX) was encapsulated in the carrier system for efficient cell penetration and nuclear targeting of drugs. An in vitro study showed an enhanced in vitro cytotoxicity and showed that the tumor volume decreased more than 5 times compared with the nontargeted system, by utilizing the drug-loaded system (FA-PECL/CPP-DOX) with active tumor cell targeting and subsequent nuclear targeting. The FA-PECL/CPP-DOX drug-loading system was well-targeted and enriched on tumor sites, resulting in significant suppression of the liver tumor growth.

High drug-loading system of hollow carbon dots-doxorubicin: preparation, in vitro release and pH-targeted research.

Hollow carbon dots (HCDs), as drug carriers, and doxorubicin (DOX), as a model drug, were selected to prepare a HCDs-DOX-loading system. First, HCDs were prepared by a hydrothermal method and characterized by transmission electron microscopy (TEM), powder X-ray diffraction (PXRD), and nuclear magnetic resonance (13C NMR), UV-vis absorption, Fourier-transform infrared (FT-IR) and X-ray photoelectron spectroscopies (XPS). The HCDs were then used to load DOX. The drug-loading system of HCDs-DOX was characterized by zeta potential measurements, and UV-vis absorption and fluorescence spectroscopies. We then studied the drug loading, formation mechanism, cytotoxicity, in vitro release and pH-targeted properties. HCDs-DOX was found to have a high drug (DOX)-loading ratio (∼42.9%) and better sustained pH targeted-release and lower cytotoxicity than those of DOX. In the HCDs-DOX system, interactions between the HCDs and DOX were electrostatic resulting in the formation of -N[double bond, length as m-dash]C-via the coupling of -NH2 (on HCDs) and -C[double bond, length as m-dash]O (on DOX). In vitro release of HCDs-DOX conformed to the Weibull model and Fick diffusion, consistent with that of free DOX. We report, for the first time, that the: (i) functional groups on the HCD surfaces (not their hollow structure) play a key role in drug loading; (ii) the carrier (HCDs) did not change the in vitro release model or mechanism of DOX before and after loading by the HCDs.

Biofunctionalization of decellularized porcine aortic valve with OPG-loaded PCL nanoparticles for anti-calcification.

Decellularized valve stents are widely used in tissue-engineered heart valves because they maintain the morphological structure of natural valves, have good histocompatibility and low immunogenicity. However, the surface of the cell valve loses the original endothelial cell coverage, exposing collagen and causing calcification and decay of the valve in advance. In this study, poly ε-caprolactone (PCL) nanoparticles loaded with osteoprotegerin (OPG) were bridged to a decellularized valve using a nanoparticle drug delivery system and tissue engineering technology to construct a new anti-calcification composite valve with sustained release function. The PCL nanoparticles loaded with OPG were prepared via an emulsion solvent evaporation method, which had a particle size of 133 nm and zeta potential of −27.8 mV. Transmission electron microscopy demonstrated that the prepared nanoparticles were round in shape, regular in size, and uniformly distributed, with an encapsulation efficiency of 75%, slow release in vitro, no burst release, no cytotoxicity to BMSCs, and contained OPG nanoparticles in vitro. There was a delay in the differentiation of BMSCs into osteoblasts. The decellularized valve modified by nanoparticles remained intact and its collagen fibers were continuous. After 8 weeks of subcutaneous implantation in rats, the morphological structure of the valve was almost complete, and the composite valve showed anti-calcification ability to a certain extent.

Synthesis of hollow nanocages MOF-5 as drug delivery vehicle to solve the load-bearing problem of insoluble antitumor drug oleanolic acid (OA)

Oleanolic acid is an antitumor traditional Chinese medicine component whose oral efficacy and clinical applications are limited because of its strong hydrophobicity. Recently, the use of metal–organic frameworks (MOFs) as drug carriers has attracted considerable research attention. In this study, the hollow structure of MOF-5 was synthesized. Its drug loading and drug release capacity were studied. The human ovarian cancer SK-OV-3 cell line was selected to study the drug loading system, cytotoxicity, and cellular uptake. We concluded that a hollow MOF with an excellent morphology was successfully fabricated in the experiment; it increased the drug loading capacity, achieved a more ideal sustained-release effect, improved the treatment efficiency of the hydrophobic Chinese medicine component, and provided a relatively efficient drug loading material.

Antimicrobial gelatin-based elastomer nanocomposite membrane loaded with ciprofloxacin and polymyxin B sulfate in halloysite nanotubes for wound dressing

Bacterial infection is a major problem world-wide, especially in wound treatment where it can severely prolong the healing process. In this study, a double drug co-delivery elastic antibacterial nanocomposite was developed by combining ciprofloxacin (CPX) and polymyxin B sulfate-loaded halloysite clay nanotubes (HNTs-B) into a gelatin elastomer. CPX nanoparticles which act against both gram positive and gram-negative bacterium were dispersed directly in the matrix, and polymyxin B sulfate was loaded in HNTs and then distributed into the matrix. The effect of CPX and HNTs-B content on the physical properties, cytotoxicity, fibroblast adhesion and proliferation, in vitro drug release behavior and anti-bacterial properties were systematically investigated. The ciprofloxacin crystals and HNT-B were distributed in the matrix uniformly. The HNTs in the drug loading system not only enhanced the matrix' tensile strength but also slowed down the release rate of the high dissoluble polymyxin B sulfate. When the amount of HNT in the matrix increased, the thermal stability and tensile strength also increased but the polymyxin B sulfate release rate decreased because the HNTs prevented the drug release inside. All the nanocomposites exhibited antimicrobial activity against both gram-negative and gram-positive bacteria with the dual combination of drugs released from the nanocomposites. Furthermore, this kind of gelatin-based nanocomposites possesses higher water-absorbing quality, low cytotoxicity, adaptable biodegradability and good elasticity which can satisfy the requirements for an ideal biomaterial for use in wound healing applications.

An efficient and self-guided chemo-photothermal drug loading system based on copolymer and transferrin decorated MoS2 nanodots for dually controlled drug release

The clinical applications of a large variety of inorganic nanomaterials have been severely limited by their long-term retention with potential toxicity in the body. Herein, we develop a self-guided photothermal nanocarrier based on MoS2 nanodots (MoS2 NDs) modified with copolymer P(OEGA-co-VBA) and targeting ligands of transferrin (Tf). The copolymer P(OEGA-co-VBA) is synthesized via RAFT polymerization and not only utilized to improve the biocompatibility of MoS2 NDs, but also efficiently load the drug doxorubicin (DOX) via acid-cleavable Schiff base bonds. Besides, thiol functionalized transferrin (Tf-SH) is anchored onto the surface of MoS2 NDs via the formation of disulfide bonds, which could further enhance the cellular engulfed of MoS2 NDs nanocarrier to HepG2 cells. The as-prepared nanocarrier is stable in physiological condition while quickly release drug upon the synergistic trigger of acidic pH and glutathione (GSH). Moreover, the modified MoS2 (DOX-POV-MoS2-Tf) nanoagents shows better therapeutic effect probably attributed to the synergistic effects of targeted uptake, pH, GSH and NIR induced localized heating, which suggest the designed MoS2 nanocarrier is promising for applications in multi-modal biomedical therapy.