Incurable bacterial infections, impenetrable microbial biofilm, and irreversible antibiotic resistance are among the most dangerous threats for humans. With few effective strategies available in antimicrobial and antibiofilm development, innovative methodologies inspired by the advances in other fields such as nanomedicine are becoming more and more attractive to realize innovative antibacterial agents. Herein, a 2D niobium carbide (Nb 2 C) MXene titanium plate (Nb 2 C@TP)-based clinical implant with practical multimodal anti-infection functions was developed. Such emerging modes are capable of destroying biofilms for direct bacteria elimination through down-regulating bacterial energy metabolism pathways, suppressing biofilm formation, and enhancing as-formed biofilm detachment via an activating accessory gene regulator. Another intriguing feature of this nanomedicine is the sensitization ability toward bacteria via photothermal transduction, which reduces the temperature necessary for bacteria eradication and mitigates possible normal tissue damage. Moreover, the Nb 2 C@TP medical implant is able to alleviate proinflammatory responses by scavenging excessive reactive oxygen species in infectious microenvironments, benefiting angiogenesis and tissue remodeling.

Magnetic-based theranostics feature a high efficiency, excellent tissue penetration, and minimal damage to normal tissues, are noninvasive, and are widely used in the diagnosis and therapy of clinical diseases. Herein, a conceptually novel magnetostrictive-piezoelectric nanocatalytic medicine (MPE-NCM) for tumor therapy is proposed by initiating an intratumoral magneto-driven and piezoelectric-catalyzed reaction using core–shell structured CoFe2O4–BiFeO3 magnetostrictive-piezoelectric nanoparticles (CFO-BFO NPs) under an alternating magnetic field. The CFO-BFO NPs catalyze the generation of cytotoxic reactive oxygen species (ROS): superoxide radicals (•O2 –) and hydroxyl radicals (•OH). The simulation calculation demonstrates the highly controllable electric polarization, facilitating the above catalytic reactions under the magnetic stimulation. Both a detailed cell-level assessment and the tumor xenograft evaluation evidence the significant tumor eradication efficacy of MPE-NCM. This study proposes an original and novel magneto-responsive nanocatalytic modality for cancer therapy, which displays promising prospects for the future clinic translation owing to its excellent catalytic dynamic responsiveness, high therapeutic efficacy, and biosafety in vivo.

The development of bacterial vaccines for inducing immunoresponse against infectious diseases such as osteomyelitis is of great signi cance and importance. However, the responsiveness of bacterial immunotherapy remains far from being satisfactory largely due to the erratic antigen epitopes of bacteria. Herein, we report an in situ vaccination strategy for the immunotherapy of bacterial infection based on an osteomyelitis model using a biomimetic nanomedicine named as HMMP, which was constructed by engineering PpIX-encapsulated hollow MnO x with a hybrid membrane exfoliated from both macrophage and tumor cell lines. The as-established HMMP features a burst bacterial antigen release as the in situ vaccine by the augmented sonodynamic treatment, and the resultant priming of antigen presenting cells for the following activations of both cellular and humoral adaptive immunities against bacterial infections. This treatment regimen not only triggers initial bacterial regression in established osteomyelitis model, also simultaneously generate robust systemic antibacterial immunity against poorly immunogenic secondary osteomyelitis in the contralateral knee as well, and additionally, confers long-lasting bacteria-speci c immune memory responses to prevent infection relapse. Thus, our study provides a proof of concept of in situ vaccination for the activation of both innate and adaptive antibacterial immune responses, providing an individual-independent bacterial immunotherapy.

OBJECTIVE:To determine whether curcumin reverses the multidrug resistance of human colon cancer cells in vitro and in vivo.METHODS:In a vincristine-resistant cell line of human colon cancer, the cell viability of curcumin-treated cells was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Rhodamine123 efflux was evaluated to detect P-glycoprotein transporter activity, and expression of the multidrug resistance protein 1 and survivin genes was analyzed by reverse transcription polymerase chain reaction and western blotting. In addition, xenograft mouse tumors were grown and treated with curcumin. The morphology of the xenografts was investigated by hematoxylin-eosin staining. The in vivo expression of the multidrug resistance gene and P-glycoprotein and survivin genes and proteins was observed using reverse transcription-polymerase chain reaction and western blotting, respectively.RESULTS:Curcumin was not obviously toxic to the vincristine-resistant human colon cancer cells at concentrations less than 25 μM, but the growth of cells was significantly inhibited. At concentrations greater than 25 μM, curcumin was toxic in a concentration-dependent manner. The sensitivity of cells to vincristine, cisplatin, fluorouracil, and hydroxycamptothecin was enhanced, intracellular Rhodamine123 accumulation was increased (p<0.05), and the expression of the multidrug resistance gene and P-glycoprotein were significantly suppressed (p<0.05). The combination of curcumin and vincristine significantly inhibited xenograft growth. The expression of the multidrug resistance protein 1 and survivin genes was significantly reduced in xenografts of curcumin-treated mice and mice treated with both curcumin and vincristine relative to control mice.CONCLUSION:Curcumin has strong reversal effects on the multidrug resistance of human colon carcinoma in vitro and in vivo.