Mesoporous Polydopamine Research Articles

Mesoporous polydopamine nanoparticles carrying peptide RL-QN15 show potential for skin wound therapy

BackgroundSkin wound healing remains a considerable clinical challenge, thus stressing the urgent need for the development of new interventions to promote repair. Recent researches indicate that both peptides and nanoparticles may be potential therapies for the treatment of skin wounds.MethodsIn the current study, the mesoporous polydopamine (MPDA) nanoparticles were prepared and the peptide RL-QN15 that was previously identified from amphibian skin secretions and exhibited significant potential as a novel prohealing agent was successfully loaded onto the MPDA nanoparticles, which was confirmed by results of analysis of scanning electron microscopy and fourier transform infrared spectroscopy. The encapsulation efficiency and sustained release rate of RL-QN15 from the nanocomposites were determined. The prohealing potency of nanocomposites were evaluated by full-thickness injured wounds in both mice and swine and burn wounds in mice.ResultsOur results indicated that, compared with RL-QN15 alone, the prohealing potency of nanocomposites of MPDA and RL-QN15 in the full-thickness injured wounds and burn wounds in mice was increased by up to 50 times through the slow release of RL-QN15. Moreover, the load on the MPDA obviously increased the prohealing activities of RL-QN15 in full-thickness injured wounds in swine. In addition, the obvious increase in the prohealing potency of nanocomposites of MPDA and RL-QN15 was also proved by the results from histological analysis.ConclusionsBased on our knowledge, this is the first research to report that the load of MPDA nanoparticles could significantly increase the prohealing potency of peptide and hence highlighted the promising potential of MPDA nanoparticles-carrying peptide RL-QN15 for skin wound therapy.Graphic abstract

Aptamer-conjugated mesoporous polydopamine for docetaxel targeted delivery and synergistic photothermal therapy of prostate cancer.

ObjectivesIt is imperative to develop efficient strategies on the treatment of prostate cancer. Here, we constructed multifunctional nanoparticles, namely AS1411@MPDA‐DTX (AMD) for targeted and synergistic chemotherapy/photothermal therapy of prostate cancer.Materials and MethodsMesoporous polydopamine (MPDA) nanoparticles were prepared by a one‐pot synthesis method, DTX was loaded through incubation, and AS1411 aptamer was modified onto MPDA by the covalent reaction. The prepared nanoparticles were characterized by ultra‐micro spectrophotometer, Fourier transform infrared spectra, transmission electron microscope, and so on. The targeting ability was detected by selective uptake and cell killing. The mechanism of AMD‐mediated synergistic therapy was detected by Western blot and immunofluorescence.ResultsThe prepared nanoparticles can be easily synthesized and possessed excellent water solubility, stability, and controlled drug release ability, preferentially in acidic context. Based on in vitro and in vivo results, the nanoparticles can efficiently target prostate cancer cells, promote DTX internalization, and enhance the antitumor effects of chemo‐photothermal therapy strategies under the NIR laser irradiation.ConclusionsAs a multifunctional nanoplatform, AS1411@MPDA‐DTX could efficiently target prostate cancer cells, promote DTX internalization, and synergistically enhance the antiprostate cancer efficiency by combining with NIR irradiation.

A multifunctional hydrogel coating to direct fibroblast activation and infected wound healing via simultaneously controllable photobiomodulation and photodynamic therapies

Bacterial infection treatment and subsequent tissue rebuilding are the main tasks of biomaterial research. To endow implants with antibacterial activity and biological functions, the material systems are usually very complicated and ineffective. Recently, the concept of photobiomodulation (PBM), or low-level laser therapy (LLLT), has attracted increasing attention in tissue repair applications but still has not obtained wide acceptance. Because of the same laser resource, PBM could simultaneously work with 660 nm laser triggered photodynamic therapy (PDT), which will significantly simplify the material system and achieve the multiple functions of antibacterial activity and biological modulation effects. Herein, we attempt to validate the effectiveness of PBM and combine PBM with a PDT-based material system. A catechol motif-modified methacrylated gelatin containing photosensitizer Chlorin e6-loaded mesoporous polydopamine nanoparticles was fabricated (GelMAc/MPDA@Ce6). This hydrogel could be tightly adhered to titanium surfaces to serve as surface coating materials or directly used as dressings. Because of the 660 nm laser-triggered ROS generation property of Ce6, GelMAc/MPDA@Ce6 exhibited a remarkable and rapid antibacterial activity when the laser power was 1 W cm−2. After bacterial elimination, when the power was adjusted to 100 mW cm−2, daily irradiation brought an excellent PBM effect: the fibroblast activation was realized to accelerate wound repair. According to our in vitro and in vivo results, the fabricated hydrogel coating possessed both antibacterial activity and fibroblast activation ability only by adjusting the power of laser irradiation, which will greatly strengthen the confidence of using PBM in broader fields and give a good example to combine PBM with traditional biomaterial design.

Tumor targeting and penetrating biomimetic mesoporous polydopamine nanoparticles facilitate photothermal killing and autophagy blocking for synergistic tumor ablation

The synergistic manipulation of autophagy blocking with tumor targeting and penetration effects to enhance cancer cell killing during photothermal therapy (PTT) remains a substantial challenge. Herein, we fabricated a biomimetic nanoplatform by precisely coating homologous prostate cancer cell membranes (CMs) onto the surface of mesoporous polydopamine nanoparticles (mPDA NPs) encapsulating the autophagy inhibitor chloroquine (CQ) for synergistically manipulating PTT and autophagy for anticancer treatment. The resulting biomimetic mPDA@CMs NPs-CQ system could escape macrophage phagocytosis, overcome the vascular barrier, and home in the homologous prostate tumor xenograft with high tumor targeting and penetrating efficiency. The mPDA NPs core endowed the mPDA@CMs NPs-CQ with good photothermal capability to mediate PTT killing of prostate cancer cells, while NIR-triggered CQ release from the nanosystem further arrested PTT-induced protective autophagy of cancer cells, thus weakening the resistance of prostate cancer cells to PTT. This combined PTT killing and autophagy blocking anticancer strategy could induce significant autophagosome accumulation, ROS generation, mitochondrial damage, endoplasmic reticulum stress, and apoptotic signal transduction, which finally results in synergistic prostate tumor ablation in vivo. This prostate cancer biomimetic nanosystem with synergistically enhanced anticancer efficiency achieved by manipulating PTT killing and autophagy blocking is expected to serve as a more effective anticancer strategy against prostate cancer. Statement of significanceAutophagy is considered as one of the most efficient rescuer and reinforcement mechanisms of cancer cells against photothermal therapy (PTT)-induced cancer cell eradication. How to synergistically manipulate autophagy blocking with significant tumor targeting and penetration to enhance PTT-mediated cancer cell killing remains a substantial challenge. Herein, we fabricated a biomimetic nanoplatform by precisely coating homologous cancer cell membranes onto the surface of mesoporous polydopamine nanoparticles with encapsulation of the autophagy inhibitor chloroquine for synergistic antitumor treatment with high tumor targeting and penetrating efficiency both in vitro and in vivo. This biomimetic nanosystem with synergistically enhanced anticancer efficiency by manipulating PTT killing and autophagy blocking is expected to serve as a more effective anticancer strategy.

H2O2 Self-Supplying and GSH-Depleting Nanoplatform for Chemodynamic Therapy Synergetic Photothermal/Chemotherapy.

Chemodynamic therapy (CDT) that utilizes Fenton-type reactions to convert endogenous hydrogen peroxide (H2O2) into hydroxyl radicals (•OH) is a promising strategy in anticancer treatment, but the overexpression of glutathione (GSH) and limited endogenous H2O2 make the efficiency of CDT unsatisfactory. Here, an intelligent nanoplatform CuO2@mPDA/DOX-HA (CPPDH), which induced the depletion of GSH and the self-supply of H2O2, was proposed. When CPPDH entered tumor cells through the targeting effect of hyaluronic acid (HA), a release of Cu2+ and produced H2O2 were triggered by the acidic environment of lysosomes. Then, the Cu2+ was reduced by GSH to Cu+, and the Cu+ catalyzed H2O2 to produce •OH. The generation of •OH could be distinctly enhanced by the GSH depletion and H2O2 self-sufficiency. Besides, an outstanding photothermal therapy (PTT) effect could be stimulated by NIR irradiation on mesoporous polydopamine (mPDA). Meanwhile, mPDA was an excellent photoacoustic reagent, which could monitor the delivery of nanocomposite materials through photoacoustic (PA) imaging. Moreover, the successful delivery of doxorubicin (DOX) realized the integration of chemotherapy, PTT, and CDT. This strategy could solve the problem of insufficient CDT efficacy caused by the limited H2O2 and overexpression of GSH. This multifunctional nanoplatform may open a broad path for self-boosting CDT and synergistic therapy.

Interfacial assembled mesoporous polydopamine nanoparticles reduced graphene oxide for high performance of waterborne epoxy-based anticorrosive coatings

Embedding two-dimension micro/nanocontainers containing corrosion inhibitors into organic coating is a well-established concept to impart the coating with enhanced barrier and self-healing feature. Herein, a versatile nanoemulsion assembly approach was used to synthesis nanocarriers combing mesoporous polydopamine nanoparticles (MPDA) with reduced graphene oxide (GO), which was employed to encapsulate corrosion inhibitors (benzotriazole, BTA) to improve the anticorrosion performance of waterborne epoxy coating. The BTA release profiles from synthesized GO with MPDA (PDAG) demonstrated the rapid pH-triggered activities to acidic corrosion environment. With the addition of BTA-loaded PDAG, the composited epoxy coatings presented self-repairing behavior and enhanced corrosion resistance during long-term immersion. The outstanding anticorrosion performance is attributed to dual-protection mechanism provided by BTA-loaded PDAG: (1) MPDA endows GO with satisfactory interface compatibilities and thus provides impermeable barrier to delay the penetration process of corrosive electrolyte; (2) corrosion inhibitors including BTA and polydopamine form the adsorption layers on bare steel surface to resist continuous corrosion at metal/coating interface.

Stromal interaction molecule 1 (STIM1) knock down attenuates invasion and proliferation and enhances the expression of thyroid-specific proteins in human follicular thyroid cancer cells

Stromal interaction molecule 1 (STIM1) and the ORAI1 calcium channel mediate store-operated calcium entry (SOCE) and regulate a multitude of cellular functions. The identity and function of these proteins in thyroid cancer remain elusive. We show that STIM1 and ORAI1 expression is elevated in thyroid cancer cell lines, compared to primary thyroid cells. Knock-down of STIM1 or ORAI1 attenuated SOCE, reduced invasion, and the expression of promigratory sphingosine 1-phosphate and vascular endothelial growth factor-2 receptors in thyroid cancer ML-1 cells. Cell proliferation was attenuated in these knock-down cells due to increased G1 phase of the cell cycle and enhanced expression of cyclin-dependent kinase inhibitory proteins p21 and p27. STIM1 protein was upregulated in thyroid cancer tissue, compared to normal tissue. Downregulation of STIM1 restored expression of thyroid stimulating hormone receptor, thyroid specific proteins and increased iodine uptake. STIM1 knockdown ML-1 cells were more susceptible to chemotherapeutic drugs, and significantly reduced tumor growth in Zebrafish. Furthermore, STIM1-siRNA-loaded mesoporous polydopamine nanoparticles attenuated invasion and proliferation of ML-1 cells. Taken together, our data suggest that STIM1 is a potential diagnostic and therapeutic target for treatment of thyroid cancer.

Tumor-Targeting and Penetrating Biomimetic Mesoporous Polydopamine Nanoparticles Manipulate Photo-Thermal Killing and Autophagy Blocking for Synergized Tumor Ablation

How to synergistically manipulate autophagy blocking with significant tumor targeting and penetration for the reinforcement of cancer cell killing during photo-thermal therapy (PTT) remains a substantial challenge. Herein, we fabricated a biomimetic nano-platform by exactly coating homologous cancer cell membranes (CMs) onto the surface of the assembly mesoporous polydopamine nanoparticles (mPDA NPs) with autophagy inhibitor chloroquine (CQ) encapsulating, for synergistically anticancer treatment manipulating PTT and autophagy. The resulting biomimetic mPDA@CMs NPs-CQ system could escape from the macrophage phagocytosis, overcome the vascular barrier, and home in the homologous tumor with high tumor targeting and penetrating efficiency. mPDA NPs core endow the mPDA@CMs NPs-CQ with excellent photo-thermal capability to mediate PTT killing of cancer cells, while NIR-triggered CQ release from mPDA@CMs NPs-CQ could further arrest PTT-induced protective autophagy of cancer cells, thus weakening the resistance of cancer cells to PTT. This PTT killing and autophagy blocking combined anticancer strategy could synergistically induce autophagosome accumulation, ROS generation, mitochondria damage, endoplasmic reticulum stress and apoptotic signal transduction, which leads to synergistic tumor cell inhibition both the in vitro and in vivo. This biomimetic nano-system with synergistically enhanced anticancer efficiency by manipulating PTT killing and autophagy blocking is expected to serve as more effective anticancer strategy.

Bowl-like mesoporous polydopamine with size exclusion for highly selective recognition of endogenous glycopeptides

It has been confirmed that endogenous glycopeptide plays an important role in a variety of pathological and physiological processes. However, direct analysis of endogenous glycopeptide is still a great challenge owing to the low abundance of endogenous glycopeptides and the presence of a large number of interfering substances such as large-sized proteins and heteropeptides in complex biological sample. Herein, we reported a novel bowl-like mesoporous polydopamine nanoparticle modified by carrageenan (denoted as MPDA@PEI@CA) with strong hydrophilicity and size-exclusion effect for high specificity enrichment of endogenous glycopeptides. Thanks to the suitable pore channel structure as well as strong hydrophilic surface, the as-prepared MPDA@PEI@CA nanoparticles exhibited prominent performance in enrichment of N-linked glycopeptide with ultrahigh selectivity (1:5000 M ratio of horseradish peroxidase (HRP) digests/bovine serum albumin (BSA) digests), low detection limit (5 fmol μL−1), outstanding size-exclusion ability (1:1000 mass of HRP/BSA), and unique reusability (five times). 125 N-glycosylation sites of 134 glycopeptides from 65 glycoproteins were identified from 2 μL sample of human serum treated with the MPDA@PEI@CA nanoparticles, which manifested the ability to enrich endogenous N-linked glycopeptides from complex biological samples. These results indicated that the bowl-like MPDA@PEI@CA nanoparticles with novel structure prepared in this work had great potential for glycopeptidome analysis.

Hollow mesoporous polydopamine nanospheres: synthesis, biocompatibility and drug delivery

Various polydopamine (PDA) nanospheres were synthesized by utilizing triblock copolymer Pluronic F127 and 1,3,5-trimethylbenzene (TMB) as soft templates. Precise morphology control of polydopamine nanospheres was realized from solid polydopamine nanospheres to hollow polydopamine nanospheres, mesoporous polydopamine nanospheres and hollow mesoporous polydopamine nanospheres (H-MPDANSs) by adjusting the weight ratio of TMB to F127. The inner diameter of the prepared H-MPDANSs can be controlled in the range of 50–100 nm, and the outer diameter is about 180 nm. Furthermore, the thickness of hollow mesoporous spherical shell can be adjusted by changing the amount of dopamine (DA). The H-MPDANSs have good biocompatibility, excellent photothermal properties, high drug loading capacity, and outstanding sustainable drug release properties. In addition, both NIR laser irradiation and acid pH can facilitate the controlled release of doxorubicin (DOX) from H-MPDANSs@DOX.

Controllable hydrogen release for gas-assisted chemotherapy and ultrasonic imaging of drug-resistant tumors

Gas-assisted therapy and diagnosis of tumors have attracted extensive interest due to their low toxicity and convenience, but are severely limited by the uncontrollable gas release. In this work, we proposed a kind of ammonia borane (AB) and doxorubicin (DOX) co-loaded and PEGylated Hollow Mesoporous Polydopamine (AB/[email protected]) nanoparticles for acid-sensitive hydrogen (H2)-assisted ultrasonic (US) imaging and chemotherapy of drug-resistant tumors. The in vitro experiment showed that as a high H2-storage molecule, AB can controllably release massive H2 in an acidic environment. For one thing, the H2 release in the acidic tumor environment and lysosomes of tumor cells in vivo helped to improve the US imaging performance; for another, it facilitated the lysosomal escape of nanoparticles, DOX release from nanoparticles, and blockage of mitochondrial respiratory chain. Furtherly, the blockage of mitochondrial respiratory chain reduced the production of triphosadenine (ATP), thereby decreasing the expression of heat shock protein 90 (HSP90) and promoting the therapeutic effect of DOX on drug-resistant tumors. Therefore, the nanoparticles provided an effective platform for controllable H2-assisted chemotherapy and US imaging of the drug-resistant tumors.

Sialic acid-engineered mesoporous polydopamine dual loaded with ferritin gene and SPIO for achieving endogenous and exogenous synergistic T2-weighted magnetic resonance imaging of HCC

BackgroundHepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis. Magnetic resonance imaging (MRI) is one of the most effective imaging methods for the early diagnosis of HCC. However, the current MR contrast agents are still facing challenges in the early diagnosis of HCC due to their relatively low sensitivity and biosafety. Thus, the development of effective MR agents is highly needed for the early diagnosis of HCC.ResultsHerein, we fabricated an HCC-targeted nanocomplexes containing SPIO-loaded mesoporous polydopamine (MPDA@SPIO), sialic acid (SA)-modified polyethyleneimine (SA-PEI), and alpha-fetoprotein regulated ferritin gene (AFP-Fth) which was developed for the early diagnosis of HCC. It was found that the prepared nanocomplexes (MPDA@SPIO/SA-PEI/AFP-Fth) has an excellent biocompatibility towards the liver cells. In vivo and in vivo studies revealed that the transfection of AFP-Fth gene in hepatic cells significantly upregulated the expression level of ferritin, thereby resulting in an enhanced contrast on T2-weighted images via the formed endogenous MR contrast.ConclusionsThe results suggested that MPDA@SPIO/SA-PEI/AFP-Fth had a superior ability to enhance the MR contrast of T2-weighted images of tumor region than the other preparations, which was due to its HCC-targeted ability and the combined T2 contrast effect of endogenous ferritin and exogenous SPIO. Our study proved that MPDA@SPIO/SA-PEI/AFP-Fth nanocomplexes could be used as an effective MR contrast agent to detect HCC in the early stage.

A novel self-coated polydopamine nanoparticle for synergistic photothermal-chemotherapy

The combination of photothermal therapy (PTT) and chemotherapy is a promising strategy to overcome the shortcomings of monotherapy. For the first time, we designed a self-coated nanoparticle formed by mesoporous polydopamine (MPDA) core and polydopamine (PDA) shell, which was used to load docetaxel and modified with hyaluronic acid (HA). The obtained nanoparticle can achieve targeted drug delivery and further exert the synergistic effect of PTT and chemotherapy. The MPDA core has high drug loading due to mesopores, and the PDA shell can prevent the drug from releasing in the non-target-site because of the pH-sensitivity of the PDA. Compared with other PDA coated nanoparticle, self-coated nanoparticle has a simpler composition and can avoid the potential toxicity caused by the introduction of other materials. Experimental results showed that it had good photothermal conversion ability both in vivo and in vitro, and could be actively targeted into tumor cells through HA-mediated targeting. Under laser irradiation, it ablated the tumors. Simple ingredient and preparation, good compatibility and obvious therapeutic effect make it have a broad application prospect in tumor therapy.

Sialic acid-modified mesoporous polydopamine induces tumor vessel normalization to enhance photodynamic therapy by inhibiting VE-cadherin internalization

Tumor hypoxia do harm to the therapeutic efficiency of photodynamic therapy (PDT) since sufficient local O2 concentration is necessary for the generation of toxic singlet O2 (1O2). Herein, a sialic acid-PEG-modified mesoporous polydopamine nanoparticle dual loaded with indocyanine green and 3PO-loaded (SPMI/3) was fabricated. Owing to the specific combination between sialic acid and E-selectin overexpressed on the inflammatory endothelial cells around tumors, SPMI/3 demonstrated a 1.39-fold higher accumulation than that of the PMI/3-treated group. After laser irradiation, SPMI/3 revealed a potent anti-tumor efficacy due to the combination therapy of PDT and photothermal therapy in the early stage of treatment. Later, thanks to the overexpression of vascular endothelial growth factor induced by PDT, the slowly released 3PO from SPMI/3 reduced by 65.20% endocytosis of VE-cadherin compared to the PBS group. Accordingly, SPMI/3 normalized tumor vessels by increasing laminin and pericyte coverage, contributing to the decreased vascular permeability and improved tissue hypoxia. All these improvements contributed to the normalized tumor vasculature and inhibition of metastasis. In conclusion, this finding provides a novel strategy to enhance PDT therapy via tumor vessel normalization.

NIR-/pH-Responsive Nanocarriers Based on Mesoporous Hollow Polydopamine for Codelivery of Hydrophilic/Hydrophobic Drugs and Photothermal Synergetic Therapy.

Combined therapy system has become an efficient strategy to overcome drug resistance and strengthen therapeutic effects. Herein, an efficient NIR-/pH-triggered dual-drug-loaded nanoplatform was designed for combined chemo-photothermal therapy. The hydrophobic anticancer drug bortezomib (BTZ) was first loaded in mesoporous polydopamine nanospheres (MPDAs) through the acid-sensitive borate ester bond. Afterward, pH-responsive carboxymethyl chitosan (CMCS) conjugated on the surface of MPDA could capture another anticancer drug doxorubicin (DOX) and exhibited controlled release behavior in an acidic tumor microenvironment. Meanwhile, under NIR laser irradiation, hyperthermia produced by the photothermal conversion agent MPDA could efficiently ablate cancer cells and further promote drug release. In vitro and in vivo experiments emphasized that the synthesized MPDA-BTZ@CMCS-DOX nanostructure exhibited efficient accumulation in the tumor site, resulting in sustained release of BTZ and DOX and realizing NIR-/pH-triggered chemotherapy and photothermal synergistic ablation of cancer.

Mesoporous Polydopamine Nanoparticles Attenuate Morphine Tolerance in Neuropathic Pain Rats by Inhibition of Oxidative Stress and Restoration of the Endogenous Antioxidant System.

Oxidative stress resulting from reactive oxygen species (ROS) is known to play a key role in numerous neurological disorders, including neuropathic pain. Morphine is one of the commonly used opioids for pain management. However, long-term administration of morphine results in morphine antinociceptive tolerance (MAT) through elevation of ROS and suppression of natural antioxidant defense mechanisms. Recently, mesoporous polydopamine (MPDA) nanoparticles (NPS) have been known to possess strong antioxidant properties. We speculated that morphine delivery through an antioxidant nanocarrier might be a reasonable strategy to alleviate MAT. MPDAs showed a high drug loading efficiency of ∼50%, which was much higher than conventional NPS. Spectral and in vitro studies suggest a superior ROS scavenging ability of NPS. Results from a rat neuropathic pain model demonstrate that MPDA-loaded morphine (MPDA@Mor) is efficient in minimizing MAT with prolonged analgesic effect and suppression of pro-inflammatory cytokines. Additionally, serum levels of liver enzymes and levels of endogenous antioxidants were measured in the liver. Treatment with free morphine resulted in elevated levels of liver enzymes and significantly lowered the activities of endogenous antioxidant enzymes in comparison with the control and MPDA@Mor-treated group. Histopathological examination of the liver revealed that MPDA@Mor can significantly reduce the hepatotoxic effects of morphine. Taken together, our current work will provide an important insight into the development of safe and effective nano-antioxidant platforms for neuropathic pain management.

Cartilage-targeting peptide-modified dual-drug delivery nanoplatform with NIR laser response for osteoarthritis therapy

Cartilage-targeting delivery of therapeutic agents is still an effective strategy for osteoarthritis (OA) therapy. Recently, scavenging for reactive oxygen species (ROS) and activating autophagy have been increasingly reported to treat OA effectively. In this study, we designed, for the first time, a dual-drug delivery system based on metal organic framework (MOF)-decorated mesoporous polydopamine (MPDA) which composed of rapamycin (Rap) loaded into the mesopores and bilirubin (Br) loaded onto the shell of MOF. The collagen II-targeting peptide (WYRGRL) was then conjugated on the surface of above nanocarrier to develop a cartilage-targeting dual-drug delivery nanoplatform (RB@MPMW). Our results indicated the sequential release of two agents from RB@MPMW could be achieved via near-infrared (NIR) laser irritation. Briefly, the rapid release of Br from the MOF shell exhibited excellent ROS scavenging ability and anti-apoptosis effects, however responsively reduced autophagy activity, to a certain extent. Meanwhile, following the NIR irradiation, Rap was rapidly released from MPDA core and further enhanced autophagy activation and chondrocyte protection. RB@MPMW continuously phosphorylated AMPK and further rescued mitochondrial energy metabolism of chondrocytes following IL-1β stimulation via activating SIRT1-PGC-1α signaling pathway. Additionally, the cartilage-targeting property of peptide-modified nanocarrier could be monitored via Magnetic Resonance (MR) and IVIS imaging. More significantly, RB@MPMW effectively delayed cartilage degeneration in ACLT rat model. Overall, our findings indicated that the as-prepared dual-drug delivery nanoplatform exerted potent anti-inflammation and anti-apoptotic effects, rescued energy metabolism of chondrocytes in vitro and prevented cartilage degeneration in vivo, which thereby showed positive performance for OA therapy.

Long‐Lasting Reactive Oxygen Species Generation by Porous Redox Mediator‐Potentiated Nanoreactor for Effective Tumor Therapy

AbstractThe therapeutic efficiency of reactive oxygen species (ROS)‐based nanotherapeutics is restrained by the rigorous production conditions of relatively sufficient and kinetically matching supply of intracellular substrates. The cumulative disruption of redox homeostasis and consequent pathology (e.g., Parkinson's disease) with low levels of substrates in living organisms may provide a promising model for ROS‐based therapy. Herein, a catechol chemistry‐mediated ternary nanostructure is prepared for long‐lasting generation of oxidative •OH in weakly acidic, low H2O2 homeostasis conditions of tumor. This platform employs mesoporous polydopamine (MPDA) as the porous redox mediator, while PDA‐induced sequential precipitation and biomineralization lead to hydroxy iron oxide (FeOOH) as the “iron reservoir,” and calcium phosphate (CaP) as the pH‐sensitive sheddable shell. In weakly acidic conditions, the CaP layer can be degraded to expose the catalytic surface of Fe‐dopamine interplay, where FeOOH dissolution, Fe(III) chelation, Fe(III) reduction, Fe(II) release take place sequentially and continuously for Fe(II) recycling and Fenton catalysis. Both in vitro and in vivo studies verify the significant inhibition of cancer cells and tumor regression, which can also be strengthened by the local photothermal heating. This work establishes the first paradigm of pathologically inspired nanohybrids of ROS generators with long‐lasting efficacy for cancer therapy.

Fabrication of a pH-responsive core-shell nanosystem with a low-temperature photothermal therapy effect for treating bacterial biofilm infection.

Recently, photothermal therapy (PTT) has been recognized as a viable alternative strategy against bacterial biofilm infection. However, the hyperthermia required for PTT to ablate a biofilm usually induces damage in normal tissues/organs nearby. Herein, we developed zeolite-based imidazole framework (ZIF-8)-coated mesoporous polydopamine (MPDA) core-shell nanoparticles and then loaded Pifithrin-μ (PES), a natural inhibitor of heat-shock protein (HSP) that plays an essential role in bacteria resisting heating-induced damage. The ZIF-8 shell of the MPDA@ZIF-8/PES nanoplatform enabled a rapid degradation in response to the acidic environment in bacterial biofilm infection, which triggered the controlled release of PES and Zn ions. As a result, HSP was remarkably suppressed for enhancing PTT efficacy upon mild near-infrared light irradiation. In addition, the release of Zn2+ also had an antibacterial/antibiofilm effect. Thus, the fabricated nanosystem was able to induce the effective elimination of the bacterial biofilm, realizing low-temperature PTT (∼45 °C) with excellent antibacterial efficacy. This work presented here not only provides a facile approach to fabricate the MPDA@ZIF-8/PES nanosystem with the responsiveness of the bacterial infection environment, but also proposes a promising low-temperature PTT strategy to treat bacterial biofilm-infection effectively.

A mesoporous polydopamine nanoparticle enables highly efficient manganese encapsulation for enhanced MRI-guided photothermal therapy.

Theranostic agents based on magnetic resonance imaging (MRI) and photothermal therapy (PTT) play an important role in tumor therapy. However, the available theranostic agents are facing great challenges such as biocompatibility, MRI contrast effect and photothermal conversion efficiency (η). In this work, mesoporous polydopamine nanoparticles (MPDAPs/Mn) were prepared on MRI and PTT combined theranostic nanoplatforms, of which the high loading manganese ions and specific surface areas enable good MRI contrast and excellent photothermal conversion efficiency, respectively. The MPDAPs/Mn have uniform morphology, good stability and biocompatibility. Meanwhile, in vitro and in vivo studies have confirmed their superior T1-weighted MRI effect and photothermal conversion efficiency. Furthermore, MPDAPs/Mn have excellent antitumor efficacy in HeLa tumor-bearing mice. Therefore, this developed MPDAPs/Mn theranostic nanoplatform could be a promising candidate for MRI-guided photothermal cancer therapy.