Abstract In situ anti‐tumor vaccination is an attractive type of cancer immunotherapy which relies on the effectiveness of dendritic cells (DCs) to engulf tumor antigens, become activated, and present antigens to T cells in lymphoid tissue. Here, a multifunctional nanocomplex based on calcium crosslinked polyaspartic acid conjugated to either a toll‐like receptor (TLR)7/8 agonist or a photosensitizer is reported. Intratumoral administration of the nanocomplex followed by laser irradiation induces cell killing and hence generation of a pool of tumor‐associated antigens, with concomitant promotion of DCs maturation and expansion of T cells in tumor‐draining lymph nodes. Suppression of tumor growth is observed both at the primary site and at the distal site, thereby hinting at successful induction of an adaptive anti‐tumor response. This strategy holds promise for therapeutic application in a pre‐operative and post‐operative setting to leverage to mutanome of the patient's own tumor to mount immunological memory to clear residual tumor cells and metastasis.
Background: Recently, combined photodynamic therapy (PDT) and photothermal therapy (PTT) has become a desired treatment for cancer. However, the development of economic, high-efficiency, and safe photosensitizers/photothermal agents remains a significant challenge. Methods: A novel nanocomposite has been developed via the assembly of iron oxide carbon dot (Fe 3 O 4 -CDs) nanoparticles and black phosphorus quantum dots (genipin [GP]-polyglutamic acid [PGA]-Fe 3 O 4 [email protected] ), and this nanocomposite shows a broad light-absorption band and a photodegradable character. Results: In vitro and in vivo assays indicated that GP-PGA-Fe 3 O 4 [email protected] were highly biocompatible and exhibited excellent tumor-inhibition efficacy, due to the synergistic PTT and PDT via a near-infrared laser. Importantly, in vivo tumor magnetic resonance imaging (MRI) results illustrated that GP-PGA-Fe 3 O 4 [email protected] can be specifically applied for enhanced T 2 MRI of tumors. This work presents the first combined application of a PDT and PTT effect deriving from BPQDs and MRI from Fe 3 O 4 -CDs, which may promote utilization of black BPQDs in biomedicine. Conclusion: As expected, GP-PGA-Fe 3 O 4 [email protected] displayed a dramatically enhanced ability to destroy tumor cells, due to the synergistic combination of PTT and PDT. Keywords: black phosphorus quantum dots, biocompatible, photothermal, photodynamic, T 2 MRI
Abstract The current nucleic acid signal amplification methods for SARS-CoV-2 RNA detection heavily rely on the functions of biological enzymes which imposes stringent transportation and storage conditions, high cost and global supply shortages. Here, a non-enzymatic whole genome detection method based on a simple isothermal signal amplification approach is developed for rapid detection of SARS-CoV-2 RNA and potentially any types of nucleic acids regardless of their size. The assay, termed non-enzymatic isothermal strand displacement and amplification (NISDA), is able to quantify 10 RNA copies.µL −1 . In 164 clinical oropharyngeal RNA samples, NISDA assay is 100 % specific, and it is 96.77% and 100% sensitive when setting up in the laboratory and hospital, respectively. The NISDA assay does not require RNA reverse-transcription step and is fast (<30 min), affordable, highly robust at room temperature (>1 month), isothermal (42 °C) and user-friendly, making it an excellent assay for broad-based testing.
After the development of portable glucose biosensor, challenges have remained to fabricate more portable devices for sensitive and reproducible detection of other biomarkers. Here, we fabricated a hand-held device for the quantification of carcinoembryonic antigen (CEA) or any other biomarkers based on electrochemiluminescence (ECL) using a bipolar electrode (BPE). The detection mechanism was based on a sandwich assay composed of a capture antibody and a secondary antibody conjugated with a robust ECL reporter. The ECL reporter was fabricated by conjugation of luminol on streptavidin-coated gold nanoparticle (Lum@SA-AuNP), leaving the biotin binding sites of the streptavidin intact for further conjugation with secondary antibody. This novel controlled functionalization strategy significantly enhanced the reproducibility and robustness of the biosensor. Moreover, an inventive parabolic reflector was implemented in the design, in order to maximize the lights to be captured by the photodiode (detector) and measured by a simple multimeter. Due to the synergetic signal amplification, the developed biosensor demonstrated a low sensitivity of 2.51 ng/ml with a linear detection range from 5 to 300 ng/ml with the ability to perform well in spiked-in samples. The designed sensing mechanism can definitely pave the way for further development of miniaturized devices in multiple formats.
Abstract Compared to other tumors, glioblastoma (GBM) is extremely difficult to treat. Recently, photothermal therapy (PTT) has demonstrated advanced therapeutic efficacy; however, because of the relatively low tissue‐penetration efficiency of laser light, its application in deep‐seated tumors remains challenging. Herein, bradykinin (BK) aggregation‐induced‐emission nanoparticles (BK@AIE NPs) are synthesized; these offer selective penetration through the blood–tumor barrier (BTB) and strong absorbance in the near‐infrared region (NIR). The BK ligand can prompt BTB adenosine receptor activation, which enhances transportation and accumulation inside tumors, as confirmed by T 1 ‐weighted magnetic resonance and fluorescence imaging. The BK@AIE NPs exhibit high photothermal conversion efficiency under 980 nm NIR laser irradiation, facilitating the treatment of deep‐seated tumors. Tumor progression can be effectively inhibited to extend the survival span of mice after spatiotemporal PTT. NIR irradiation can eradicate tumor tissues and release tumor‐associated antigens. It is observed that the PTT treatment of GBM‐bearing mice activates natural killer cells, CD3 + T cells, CD8 + T cells, and M1 macrophages in the GBM area, increasing the therapeutic efficacy. This study demonstrates that NIR‐assisted BK@AIE NPs represent a promising strategy for the improved systematic elimination of GBMs and the activation of local brain immune privilege.
To meet the requirements of biomedical applications in the antibacterial realm, it is of great importance to explore nano-antibiotics for wound disinfection that can prevent the development of drug resistance and possess outstanding biocompatibility. Therefore, we attempted to synthesize an atomically dispersed ion (Fe) on phenolic carbon quantum dots (CQDs) combined with an organic photothermal agent (PTA) (Fe@SAC CQDs/PTA) via a hydrothermal/ultrasound method. Fe@SAC CQDs adequately exerted peroxidase-like activity while the PTA presented excellent photothermal conversion capability, which provided enormous potential in antibacterial applications. Based on our work, Fe@SAC CQDs/PTA exhibited excellent eradication of Escherichia coli (>99% inactivation efficiency) and Staphylococcus aureus (>99% inactivation efficiency) based on synergistic chemodynamic therapy (CDT) and photothermal therapy (PTT). Moreover, in vitro experiments demonstrated that Fe@SAC CQDs/PTA could inhibit microbial growth and promote bacterial biofilm destruction. In vivo experiments suggested that Fe@SAC CQDs/PTA-mediated synergistic CDT and PTT exhibited great promotion to wound disinfection and recovery effects. This work indicated that Fe@SAC CQDs/PTA could serve as a broad-spectrum antimicrobial nano-antibiotic, which was simultaneously beneficial for bacterial biofilm eradication, wound disinfection, and wound healing.
With advances in nanoparticle (NP) synthesis and engineering, nanoscale agents with both therapeutic and diagnostic functions have been increasingly exploited for cancer management.Herein, we synthesized a new type of zwitterionic polymer-gated Au@TiO 2 core-shell nanoparticles, which showed that they could selectively target and efficiently eliminate cancer cells via photothermal therapy (PTT), photodynamic therapy (PDT), pH/NIR-induced drug release, and cationic therapy.Methods: In the present study, the multifunctional therapeutic agent [Mn@P(CitAPDMAEMA) @Au@TiO 2 @DOX] was prepared to treat cancer with imaging-guided combination method.Firstly, Au@TiO 2 core-shell nanoparticles (NPs) were synthesized.Taking advantage of broad and strong photoabsorption and reactive oxygen species (ROS) generation, Au@TiO 2 core-shell NPs facilitated the single light-induced PTT and PDT.Next, a chemotherapy drug doxorubicin (DOX) was loaded into Au@TiO 2 core-shell NPs.Then, a biocompatible zwitterionic polymer P(CitAPDMAEMA) was grafted to improve the hemocompatibility of NPs and prolong the circulation time.The polymer also served as a capping or switching material for pH-triggered drug release.In addition, the cationic nature of P(CitAPDMAEMA) eased the binding to human cervical cancer (HeLa) cells and effectively inhibited their growth in acidic environments (termed cationic therapy).Moreover, with Mn 2+ ions immanently chelated, Mn@P(CitAPDMAEMA)@Au@TiO 2 @ DOX NPs were able to provide enhanced contrast under T 1 -or T 2 -weighted magnetic resonance imaging (MRI). Results:The in vitro and in vivo anticancer experiments demonstrated the tumor was effectively inhibited with minimal side effects by the multifunctional NPs.Conclusions: As far as we know, this is the first presentation of four therapeutic methods into one nanomaterial, which will open up a new dimension for the design of combined treatment.
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