**5. Conclusions and Outlooks**

Pdots have become an important material for point-of-care testing and in vivo imaging, which greatly assist the diagnosis and treatment of diseases. In this review, several preparation methods are described to demonstrate ways to obtain Pdots with different ranges of particle diameter. In addition, Pdots have excellent photophysical properties and performance, including large absorption cross section, high quantum yield, good photostability and low toxicity. Moreover, recent studies have reported different approaches to further improve these properties. In addition to the size and performance, Pdots can be adapted to special application aims and environments though several modification and functionalization methods. All these methods mentioned in this review indicate that the size, properties and function of Pdots can be tuned for practical applications, suggesting greater utility compared to the traditional materials. For biosensing application, Pdots biosensors based on FRET or electron transfer have been used for the detection of glucose, phenylalanine, NAD and tumor markers, all of which have shown good assay results with convenient, accurate and rapid characteristics. For in vivo bioimaging applications, Pdots can be used as optical probes for fluorescence imaging or as contrast agents for NIR-II PAI, which not only have deeper penetration depth, higher brightness, better resolution and higher contrast efficiency, but also exhibit rapid metabolic capacity relevant for biosafety. Such a large range of applications and outstanding results have proven the significance of Pdots for point-of-care diagnostics and in vivo bioimaging.

Considering the highly homogeneous product landscape, Pdots-based diagnostic techniques have great potential in the sensing and imaging markets. However, Pdots for disease diagnosis and treatment are mainly in the research stage, which still have some distance from clinical application. In this period of rapid development in the materials sector, relevant research on Pdots needs to constantly combine new techniques and explore more applications. In our opinion, future work in this field mainly includes the following aspects: (1) To develop a large-scale, eco-friendly and low-cost method for the preparation of Pdots. (2) Optimizing biofunctionalization strategies to obtain smart Pdots-based probes with stimuli-responsive targeting. (3) Pdots with ultra-small particles (<10 nm) and uniform particle size that are particularly suitable for the development of optical transducers. Furthermore, for in vivo applications, the ultra-small-size Pdots can further enhance biodistribution and rapid metabolism. The biological metabolism of nanoparticles is currently the biggest problem limiting their clinical application. (4) The exploration of NIR-II Pdots can improve the penetration depth of light in biological tissues. Although NIR-II imaging and therapy have received considerable attention, biosensing applications of the NIR-II window are largely unexplored. (5) Emerging hybrid nanocomposites composed of organic and inorganic nanomaterials are expected to endow the nanosystems of Pdots with complementary multimodal imaging modalities and synergistic therapeutics. (6) Computational simulations can also help us design functionalized Pdots for specific biomedical applications. With the rapid development of artificial intelligence, it will be more effective to design rational Pdots for clinical translation.

**Author Contributions:** Conceptualization, S.D., Z.H. and H.C.; writing—original draft preparation, S.D.; writing—review and editing, L.L., J.Z., Y.W., Z.H. and H.C.; visualization, S.D., Z.H. and H.C.; supervision, Z.H. and H.C.; funding acquisition, H.C. All authors have read and agreed to the published version of the manuscript.

**Funding:** We thank the National Natural Science Foundation of China (Grant No. 82202296) and Central South University for the financial support.

**Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** Not applicable.

**Conflicts of Interest:** The authors declare no conflict of interest.

#### **References**


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**Cong Wen 1, Rongsheng Li 2, Xiaoxia Chang <sup>3</sup> and Na Li 1,\***


**Abstract:** Metal-organic frameworks (MOFs)-based optical nanoprobes for luminescence and surfaceenhanced Raman spectroscopy (SERS) applications have been receiving tremendous attention. Every element in the MOF structure, including the metal nodes, the organic linkers, and the guest molecules, can be used as a source to build single/multi-emission signals for the intended analytical purposes. For SERS applications, the MOF can not only be used directly as a SERS substrate, but can also improve the stability and reproducibility of the metal-based substrates. Additionally, the porosity and large specific surface area give MOF a sieving effect and target molecule enrichment ability, both of which are helpful for improving detection selectivity and sensitivity. This mini-review summarizes the advances of MOF-based optical detection methods, including luminescence and SERS, and also provides perspectives on future efforts.

**Keywords:** metal–organic frameworks; luminescence; surface-enhanced Raman spectroscopy; multiplexed detection
