Ag 2 Te is one of the most promising semiconductors with a narrow band gap and low toxicity; however, it remains a challenge to tune the emission of Ag 2 Te quantum dots (QDs) precisely and continuously in a wide range. Herein, Ag 2 Te QDs emitting from 950 to 2100 nm have been synthesized via trialkylphosphine-controlled growth. Trialkylphosphine has been found to induce the dissolution of small-sized Ag 2 Te QDs due to its stronger ability to coordinate to the Ag ion than that of 1-octanethiol, predicated by the density functional theory. By controlling this dissolution effect, the monomer supply kinetics can be regulated, achieving precise size control of Ag 2 Te QDs. This synthetic strategy results in state-of-the-art silver-based QDs with emission tunability. Only by taking advantage of such an ultrawide emission has the sizing curve of Ag 2 Te been obtained. Moreover, the absolute photoluminescence quantum yield of Ag 2 Te QDs can reach 12.0% due to their well-passivated Agenriched surface with a density of 5.0 ligands/nm 2 , facilitating noninvasive in vivo fluorescence imaging. The high brightness in the long-wavelength near-infrared (NIR) region makes the cerebral vasculature and the tiny vessel with a width of only 60 μm clearly discriminable. This work reveals a nonclassical growth mechanism of Ag 2 Te QDs, providing new insight into precisely controlling the size and corresponding photoluminescence properties of semiconductor nanocrystals. The ultrasmall, low-toxicity, emission-tunable, and bright NIR-II Ag 2 Te QDs synthesized in this work offer a tremendous promise for multicolor and deep-tissue in vivo fluorescence imaging.
Monitoring specific immune cells in vivo will provide significant information for improving the therapeutic effect of immunotherapy. Herein, the in vivo twocolor fluorescence molecular imaging of an important immune cell, myeloid-derived suppressor cell (MDSC), was realized by using quantum dot (QD)-based nanoprobes with non-overlap emission in the second near-infrared window (NIR-II, 1000−1700 nm). NIR-IIa and NIR-IIb QDs were conjugated with two MDSC-specific antibodies, respectively, and targeted the in vivo MDSCs together. Due to the suppressed photon scattering and diminished autofluorescence in the NIR-II window, the distribution of MDSCs in different organs and tissues was clearly revealed in a non-invasive way by the colocalization of two-color fluorescence from nanoprobes. The high-resolution imaging further confirmed the exact distribution of MDSCs in tumor immune microenvironment (TIME). Our results demonstrated that NIR-II fluorescence nanoprobes with molecular targeting ability provided a powerful tool for monitoring the dynamic change of immune cell populations in TIME in vivo, thus guiding the choice of clinical medicine and evaluating the therapeutic effect.
The advantages of fluorescence bioimaging in the second near‐infrared (NIR II, 1000–1700 nm) window are well known; however, current NIR II fluorescent probes for in vivo tumor imaging still have many shortcomings, such as low fluorescence efficiency, unstable performance under in vivo environments, and inefficient enrichment at tumor sites. In this study, Ag2Te quantum dots (QDs) that emit light at a wavelength of 1300 nm are assembled with poly(lactic‐co‐glycolic acid) and further encapsulated within cancer cell membranes to overcome the shortcomings mentioned above. The as‐prepared ≈100 nm biomimetic nanobioprobes exhibit ultrabright (≈60 times greater than that of free Ag2Te QDs) and highly stable (≈97% maintenance after laser radiation for 1 h) fluorescence in the NIR II window. By combining the active homotypic tumor targeting capability derived from the source cell membrane with the passive enhanced permeation and retention effect, improved accumulation at tumor sites ((31 ± 2)% injection dose per gram of tumor) and a high tumor‐to‐normal tissue ratio (13.3 ± 0.7) are achieved. In summary, a new biomimetic NIR II fluorescent nanobioprobe with ultrabright and stable fluorescence, homotypic targeting and good biocompatibility for enhanced in vivo tumor imaging is developed in this study.
Checkpoint inhibitors and T-cell therapies have highlighted the critical role of T cells in anti-cancer immunity. However, limitations associated with these treatments drive the need for alternative approaches. Here, we engineer red blood cells into artificial antigen-presenting cells (aAPCs) presenting a peptide bound to the major histocompatibility complex I, the costimulatory ligand 4-1BBL, and interleukin (IL)-12. This leads to robust, antigen-specific T-cell expansion, memory formation, additional immune activation, tumor control, and antigen spreading in tumor models in vivo. The presence of 4-1BBL and IL-12 induces minimal toxicities due to restriction to the vasculature and spleen. The allogeneic aAPC, RTX-321, comprised of human leukocyte antigen-A*02:01 presenting the human papilloma virus (HPV) peptide HPV16 E711-19, 4-1BBL, and IL-12 on the surface, activates HPV-specific T cells and promotes effector function in vitro. Thus, RTX-321 is a potential ‘off-the-shelf’ in vivo cellular immunotherapy for treating HPV + cancers, including cervical and head/neck cancers.
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