Micro/nanorobots
have been extensively explored as a tetherless
small-scale robotic biodevice to perform minimally invasive interventions
in hard-to-reach regions. Despite the emergence of versatile micro/nanorobots
in recent years, matched in vivo development remains
challenging, limited by unsatisfactory integration of core functions.
Herein, we report a polydopamine (PDA)-coated magnetic microswimmer
consisting of a magnetized Spirulina (MSP) matrix and PDA surface. Apart from the properties of the existing
MSP (e.g., robust propulsion, natural fluorescence,
tailored biodegradation, and selective cytotoxicity), the introduced
PDA coating enhances the photoacoustic (PA) signal and photothermal
effect of the MSP, thus making PA image tracking and photothermal
therapy possible. Meanwhile, the PDA’s innate fluorescence
quenching and diverse surface reactivity allows an off–on fluorescence
diagnosis with fluorescence probes (e.g., coumarin
7). As a proof of concept, real-time image tracking (by PA imaging)
and desired theranostic capabilities of PDA-MSP microswimmer swarms
are demonstrated for the treatment of pathogenic bacterial infection.
Our study suggests a feasible antibacterial microrobot for in vivo development and a facile yet versatile functionalization
strategy of micro/nanorobots.
The occurrence of a viable but nonculturable (VBNC) state in bacteria may dramatically underestimate the health risks associated with drinking water. Therefore, the potential for UV treatment to induce a VBNC state in Escherichia coli and Pseudomonas aeruginosa was investigated. UV disinfection effectively reduced the culturability of E. coli and P. aeruginosa, with the destruction of nucleic acids demonstrated using gadA long gene fragment qPCR amplification. Following UV radiation, copy numbers for the high transcriptional levels of the 16S rRNA gene varied insignificantly in both strains, confirming results from plate counting assays indicating that VBNC states were induced in both strains. Furthermore, the virulence genes gadA and oprL remained highly expressed, suggesting that the VBNC bacteria still displayed pathogenicity. Propidium monoazide qPCR indicated that cell membranes remained intact even at a UV dose of 300 mJ/cm(2). The RT-qPCR results after UV and chlorine treatments in E. coli were significantly different (8.41 and 5.59 log units, respectively), further confirming the induction of VBNC bacteria induced by UV radiation. Finally, resuscitation was achieved, with E. coli showing greater resuscitation ability than P. aeruginosa. These results systematically revealed the potential health risks of UV disinfection and strongly suggest a combined disinfection strategy.
The efficacy of photosensitizers in cancer phototherapy is often limited by photobleaching, low tumor selectivity, and tumor hypoxia. Assembling photosensitizers into nanostructures can improve photodynamic therapy efficacy and the safety profile of photosensitizers. Herein by employing supramolecular assembly, enhanced theranostic capability of Mn2+-assisted assembly of a photosensitizer (sinoporphyrin sodium, DVDMS) is demonstrated. A tumor environment-triggered coassembly strategy is further developed to form Mn/DVDMS nanotheranostics (nanoDVD) for cancer phototherapy. MnO2 nanosheets serve as a highly effective DVDMS carrier and in situ oxygen and nanoDVD generator. In MCF-7 cells and xenograft tumors, MnO2/DVDMS is reduced by glutathione (GSH) and H2O2 and reassembled into nanoDVD, which can be monitored by activated magnetic resonance/fluorescence/photoacoustic signals. Intriguingly, the decrease of GSH, the production of O2, and the formation of nanoDVD are shown to be synergistic with phototherapy to improve antitumor efficacy in vitro and in vivo, offering a new avenue for cancer theranostics.
Ligand-targeted delivery of drug molecules to various types of tumor cells remains a major challenge in precision medicine. Inspired by the secretion process and natural cargo delivery functions of natural exosomes, biomimetic synthetic strategies are exploited to prepare biofunctionalized liposome-like nanovesicles (BLNs) that can artificially display a wide variety of targeting protein/peptide ligands and directly encapsulate medical agents for enhanced drug delivery. Here, as a proof of concept, genetically engineered BLNs, which display human epidermal growth factor (hEGF) or anti-HER2 Affibody as targeting moieties, are developed to, respectively, target two types of tumor cells. Notably, in comparison to synthetic liposomes covalently coupled with hEGF, it is demonstrated in this work that biosynthetically displayed hEGF ligands on BLNs possess higher biological activities and targeting capabilities. Additionally, treatments with doxorubicin-loaded BLNs displaying Affibody ligands exhibit much better antitumor therapeutic outcomes than clinically approved liposomal doxorubicin (Doxil) in HER2-overexpressing BT474 tumor xenograft models. These data suggest that BLN is suitable as a potent surrogate for conventional proteoliposomes or immunoliposomes as a result of excellent targeting capacities and facile production of BLNs.
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