Monolayer LDH Nanosheets with Ultrahigh ICG Loading for Phototherapy and Ca2+-Induced Mitochondrial Membrane Potential Damage to Co-Enhance Cancer Immunotherapy.

Tumor recurrence and metastasis are the main causes of cancer mortality; traditional chemotherapeutic drugs have severe toxicity and side effects in cancer treatment. To overcome these issues, here, we present a pH-responsive, self-destructive intelligent nanoplatform for magnetic resonance/fluorescence dual-mode image-guided mitochondrial membrane potential damage (MMPD)/photodynamic (PDT)/photothermal (PTT)/immunotherapy for breast cancer treatment with external near infrared (NIR) light irradiation. To do so, we construct multifunctional monolayer-layered double hydroxide (LDH) nanosheets (MICaP), co-loading indocyanine green (ICG) with ultrahigh loading content realized via electrostatic interactions, and calcium phosphate (Ca3(PO4)2) coating via biomineralization. Such a combined therapy design is featured by the outstanding biocompatibility and provokes immunogenic cell death (ICD) of tumors toward cancer immunotherapy. The active transport of excess Ca2+ released from pH-sensitive Ca3(PO4)2 can induce MMPD of tumor cells to minimize oxygen consumption in the tumor microenvironment (TME). The presence of ICG not only generates singlet oxygen (1O2) to induce apoptosis by photodynamic therapy (PDT) but also initiates tumor cell necrosis by photothermal therapy (PTT) under near-infrared (NIR) light radiation. Eventually, the immune response generated by MMPD/PDT/PTT greatly promotes a cytotoxic T lymphocyte (CTL) response that can limit tumor growth and metastasis. Both in vitro and in vivo studies indeed illustrate outstanding antitumor efficiency and outcomes. We anticipate that such precisely designed nanoformulations can contribute in a useful and advantageous way that is conducive to explore novel nanomedicines with notable values in antitumor therapy.

Starvation-assisted and photothermal-thriving combined chemo/chemodynamic cancer therapy with PT/MR bimodal imaging.

Chemodynamic therapy (CDT) reflects a novel reactive oxygen species (ROS)-related cancer therapeutic approach. However, CDT monotherapy is often limited by weak efficacy and insufficient endogenous H2O2. Herein, a multifunctional combined bioreactor (MnFe-LDH/MTX@GOx@Ta, MMGT) relying on MnFe-layered double hydroxide (MnFe-LDH) loaded with methotrexate (MTX) and coated with glucose oxidase (GOx)/tannin acid (Ta) is established for applications in H2O2 self-supply and photothermal enhanced chemo/chemodynamic combined therapy along with photothermal (PT) /magnetic resonance (MR) dual-modality imaging ability for cancer treatment. Once internalized into tumor cells, MMGT achieves starvation therapy by catalyzing the oxidation of glucose with GOx, accompanied by the regeneration of H2O2, enabling a Fenton-like reaction to accomplish GOx catalytic amplified CDT. Moreover, MMGT manifests significant tumor-killing ability through improved CDT performance with outstanding photothermal conversion efficiency (η = 52.2%) under 808 nm laser irradiation. In addition, the release of Mn2+ from MnFe-LDH in a solid tumor can significantly enhance T1-contrast MR imaging signals. Combined with MnFe-LDH-induced PT imaging under 808 nm laser irradiation, a dual-modality imaging directed theranostic nanoplatform has been developed. The present study provides a new strategy to design H2O2 self-supply and ROS evolving NIR light-absorption theranostic nanoagent for highly efficient and combined chemo/chemodynamic cancer treatment.

MnO2 coated nanotheranostic LDH for synergistic cascade chemo/chemodynamic cancer therapy under the guidance of MRI-targeted diagnosis.

Integrating magnetic resonance imaging (MRI)-targeted diagnosis with synergistic cascade treatments, such as chemo/chemodynamic therapy (CT/CDT), is highly desired for promoting the antitumor performance; however, the rational design of such "all-in-one" nanomedicine is still in its infancy. In this report, using MnO2 coated layered dihydroxide (LDH) as a carrier to load chemotherapy molecule 5-flurouracil (5-FU), a novel tumor microenvironment (TME) regulating nanodrug is formed: LDH/5-FU@MnO2. Combined guidance of CT/CDT and MRI is used to realize synergistic diagnosis and enhanced anti-tumor efficacy. MnO2 is converted into Mn2+ in the presence of reducing agent GSH, the in situ generated Mn2+, not only serves as the chemical fuel for the Fenton reaction, combining H2O2 depletion and ˙OH generation, but can also be used as a nuclear magnetic contrast agent for MRI. Moreover, the tumor acidic environment is able to trigger 5-FU release for initiating chemotherapy in the tumor zone. This "all-in-one" LDH/5-FU@MnO2 nanomedicine integrating multiple treatment modalities and magnetic resonance imaging properties, causes persistent modulation of the TME and exhibits effective antitumor theranostic performance. Such a sophisticated nanomedicine design not only achieves improved CT/CDT antitumor efficiency, but also realizes the activatable magnetic resonance imaging. This strategy combines the merits of each treatment, significantly enhancing the anticancer efficacy, and is anticipated to display promising potentials in the clinical translation plans.

Promotion of the osteogenic activity of an antibacterial polyaniline coating by electrical stimulation.

Electrical stimulation (ES) exhibits a positive role in promoting the cell activity of osteoblasts. Conducting polymers have the advantages of biocompatibility, good environmental stability and easy synthesis, which have been widely used as charge carriers for electrical stimulation; moreover, considering clinical applications, biomaterial-related infection is an important issue that needs to be solved. Thus, conducting polymers with both antibacterial and osteogenic properties are highly demanded for effect repair. However, it remains a challenge to combine these two characteristics efficiently in a simple way. Herein, an Ag-loaded poly(amide-amine) dendrimer was prepared by a simple chemical reduction procedure, which acted as a dopant for the polymerization of polyaniline (PANI) on biomedical titanium (Ti) sheets. The obtained PANI coating showed outstanding antibacterial properties against Gram-negative (E. coli) and Gram-positive (S. aureus) microbes with a 1000-fold increase when compared with that of pure Ti. In addition, note that the polymer coating together with ES facilitated the proliferation and differentiation of MC3T3. The alkaline phosphatase (ALP) activity and intracellular calcium content of the cells showed a 19.09% and 24.02% increase, respectively, when compared with the case of electrically stimulated Ti after 12 days. Moreover, the existence of PAMAM facilitated mineralization. The strategy developed herein is simple and can be easily manipulated, which shows potential applications in the coating of implants for hard tissue repair.

A glassy carbon electrode modified with molecularly imprinted poly(aniline boronic acid) coated onto carbon nanotubes for potentiometric sensing of sialic acid.

A potentiometric sensor for sialic acid (SA) was developed based on molecular imprinting technique. The sensor was fabricated by modifying carbon nanotubes (CNT) and an SA-imprinted poly(aniline boronic acid) (PABA) film on a glassy carbon electrode (GCE). The detection strategy capitalizes on the change of electrochemical potential resulting from boronic acid-SA interaction. The imprinted PABA combines the functions of SA-binding boronic acid groups and the imprinting effect, thus endowing it with both chemical and sterical recognition capability. The imprint factor (IF, compared to a non-molecularly imprinted polymer) is 1.74. The sensor can well differentiate SA from its analogs at physiological pH values and has a linear potentiometric response (R2 = 0.998) in 80 µM to 8.2 mM SA concentrations range with a detection limit of 60 µM (at S/N = 3). The sensor was applied to the determination of SA in serum samples and gave recoveries between 93% and 105%. Graphical abstract Schematic presentation of the fabrication of a sialic acid (SA) imprinted poly(aniline boronic acid) (PABA)/CNT modified electrode. The electrode can well differentiate SA from its analogs at physiological pH and determine SA in human serum samples with satisfactory recoveries of 93%-105%.

One-step phosphorylated poly(amide-amine) dendrimer loaded with apigenin for simultaneous remineralization and antibacterial of dentine.

Dental caries, starting from demineralization of enamel and dentine, is closely related with acid-producing bacteria in oral cavity, for example, Streptococcus mutans. Remineralization is an efficient way to prevent the disease progression and facilitate the therapy of incipient caries. Therefore, for the purpose of effective dentine repair, remineralization and antibacterial should be combined simultaneously. However, most of the literatures only focus on one single aspect, while combing remineralization and antibacteria for dentine repair in one system is rarely reported. Here in this work, phosphoryl-terminated poly(amide-amine) dendrimers were loaded with apigenin, a water-nonsoluble drug antibacterial agains Streptococcus mutans. The apigenin-loaded dendrimers bind strongly with dentine, which further induce dentine tubules occlusion through mineralization in artificial saliva, and the release of apigenin can prevent further erosion of dentine by bacteria. Meanwhile, the phosphorylated dendrimers are easily prepared by one-step modification of poly(amide-amine) and exhibit good cytocompatibility. This strategy developed here can provide reference for the design of effective anti-caries materials.