Immunoactivation by Cutaneous Blue Light Irradiation Inhibits Remote Tumor Growth and Metastasis.

An improved innate immunity will respond quickly to pathogens and initiate efficient adaptive immune responses. However, up to now, there have been limited clinical ways for effective and rapid consolidation of innate immunity. Here, we report that cutaneous irradiation with blue light of 450 nm rapidly stimulates the innate immunity through cell endogenous reactive oxygen species (ROS) regulation in a noninvasive way. The iron porphyrin-containing proteins, mitochondrial cytochrome c (Cyt-c), and cytochrome p450 (CYP450) can be mobilized by blue light, which boosts electron transport and ROS production in epidermal and dermal tissues. As a messenger of innate immune activation, the increased level of ROS activates the NF-κB signaling pathway and promotes the secretion of immunomodulatory cytokines in skin. Initiated from skin, a regulatory network composed of cytokines and immune cells is established through the circulation system for innate immune activation. The innate immunity activated by whole-body blue light irradiation inhibits tumor growth and metastasis by increasing the infiltration of antitumor neutrophils and tumor-associated macrophages. Our results elucidate the remote immune modulation mechanism of blue light and provide a clinically applicable way for innate immunity activation.

Tripeptides Ghk and GhkCu-modified silver nanoparticles for enhanced antibacterial and wound healing activities.

Bacterial skin infections represent a major healthcare concern that can delay healing and threaten human health. Silver nanoparticles (AgNPs) have been widely used for antimicrobial purposes; however, their high toxicity limits their applications. Therefore, there is an urgent need to develop simple and efficient therapeutic approaches for treating bacterial infections and promoting wound healing. Here, novel tripeptide (Ghk and GhkCu)-modified AgNPs were developed and subsequently evaluated their antibacterial efficacy against four pathogenic bacterial isolates, cytotoxic properties, and therapeutic effects as a topical treatment for infected wounds. Spherical GhkAgNPs and GhkCuAgNPs with average sizes of 45.92 nm and 56.82 nm exhibited potential antibacterial activity, with a MIC concentration of 8 µg/ml against S. aureus and E. coli. Both AgNPs showed superior bactericidal effects against S. aureus, with complete inhibition after 7 days of treatment. Cytotoxicity assays revealed IC50 (half maximal inhibitory concentrations) values ranging from 6.75 to 6.99 µg/ml in L929 cells. GhkAgNPs displayed accelerated cell migration and facilitated healing up to 92% after 12 h. Furthermore, topical applications of GhkAgNPs and GhkCuAgNPs to S. aureus-infected wounds demonstrated enhanced in vivo wound healing efficacy compared to control groups, as evidenced by increased regenerated epidermal thickness, improved collagen deposition, and downregulation of TNF-α expression. Hence concluded that these novel tripeptides Ghk and GhkCu-modified AgNPs exhibited potent antibacterial effects and significantly promoted wound healing properties.

Quasi-MOF-Engineered MnOx /CeBTC Multinanozyme as a Robust Self-Cascade ROS Generator toward Antibacterial Face Mask.

It is of great importance to endow personal protective equipments with bactericidal property combating against infected pathogens. Nanozyme that can generate reactive oxygen species (ROS) in an enzyme-catalytic manner is regarded as a novel and promising nanobactericide. But until now, very rare of them is designed specifically for personal protective equipments. In this study, a multinanozyme of manganese oxide supported on Ce-containing MOF (CeBTC) is constructed with post-engineering via a quasi-metal-organic framework (MOF) strategy (denoted as MnOx /q-CeBTC). The strategy enables a full exposure of the metal cluster nodes, introduction of new active Mn─O─Ce bonds and strengthens interaction between the metal nodes and the guest oxide. As an advanced multinanozyme, the MnOx /q-CeBTC exhibits excellent multiple enzymatic activities at low temperature, and enables abundant and self-cascade ROS generation without H2 O2 addition. This empowers it with high efficiency in bacteria killing, which is also reflected when incorporated into face mask to combat against pathogen invasion even at low temperature. The results achieved in this work provide guidance for rational design of effective bactericide based on nanozyme and broaden their application in personal protective equipment and other fields.

Smart Bactericidal Capsules Based on Cationic Luminescent Nanoclusters for Controllable Treatment of Drug-Resistant Bacterial Infection.

Effective treatment of drug-resistant bacteria infected wound has been a longstanding challenge for healthcare systems. In particular, the development of novel strategies for controllable delivery and smart release of antimicrobial agents is greatly demanded. Herein, the design of biodegradable microcapsules carrying bactericidal gold nanoclusters (AuNCs) as an attractive platform for the effective treatment of drug-resistant bacteria infective wounds is reported. AuNC capsules are fabricated via the well-controlled layer-by-layer strategy, which possess intrinsic near-infrared fluorescence and good biocompatibility. Importantly, these AuNC capsules exhibit strong, specific antibacterial activity toward both S. aureus and methicillin-resistant S. aureus (MRSA). Further mechanistic studies by fluorescence confocal imaging and inductively coupled plasma mass spectrometry reveal that these AuNC capsules will be degraded in the S. aureus environment rather than E. coli, which then controllably release the loaded cationic AuNCs to exert antibacterial effect. Consequently, these AuNC capsules show remarkable therapeutic effect for the MRSA infected wound on a mouse model, and intrinsic fluorescence property of AuNC capsules enables in situ visualization of wound dressings. This study suggests the great potential of microcapsule-based platform as smart carriers of bactericidal agents for the effective treatment of drug-resistant bacterial infection as well as other therapeutic purposes.

Chirality-Dependent Angiogenic Activity of MoS2 Quantum Dots toward Regulatable Tissue Regeneration.

Despite great advances in understanding the biological behaviors of chiral materials, the effect of chirality-configured nanoparticles on tissue regeneration-related biological processes remains poorly understood. Herein, the chirality of MoS2 quantum dots (QDs) is tailored by functionalization with l-/d-penicillamine, and the profound chiral effects of MoS2 QDs on cellular activities, angiogenesis, and tissue regeneration are thoroughly investigated. Specifically, d-MoS2 QDs show a positive effect in promoting the growth, proliferation, and migration of human umbilical vein endothelial cells. The expression of vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), and fibroblast growth factor (FGF) in d-MoS2 QDs group is substantially up-regulated, resulting in enhanced tube formation activity. This distinct phenomenon is largely due to the higher internalization efficiency of d-MoS2 QDs than l-MoS2 QDs and chirality-dependent nano-bio interactions. In vivo angiogenic assay shows the expression level of angiogenic markers in newly-formed skin tissues of d-MoS2 QDs group is higher than that in l-MoS2 QDs group, leading to an accelerated re-epithelialization and improved skin regeneration. The findings of chirality-dependent angiogenesis activity of MoS2 QDs provide new insights into the biological activity of MoS2 nanomaterials, which also opens up a new path to the rational design of chiral nanomaterials for tissue regeneration application.

Blue light promotes vitamin C-mediated ferroptosis of melanoma through specifically upregulating transporter SVCT2 and generating Fe2.

Vitamin C (VC)-based cancer therapy is a promising therapeutic approach for a variety of cancers due to its profound effects on redox reactions and metabolic pathways. However, high administration dosage of VC for necessary therapeutic efficacy for cancers increases the risk of overt side effects and limits its clinical use. Here, we show cutaneous blue light irradiation can specifically upregulate the sodium-dependent vitamin C transporter 2 (SVCT2) of the tumor and increase effectively the VC concentration at the tumor sites by an overall low dosage administration. In the mouse melanoma model, blue light stimulates the SVCT2 expression through the nuclear factor-kappa B (NF-κB) signaling pathway both in vitro and in vivo. The increased cellular VC together with Fe2+ generated by blue light simultaneously elevate cellular oxidative stress and trigger the ferroptosis of melanoma. With this revealed mechanism, the synergistic actions of blue light on the VC transporter and Fe2+ generation lead to a ca. 20-fold reduction in the administration dosage of VC with an effective melanoma elimination and prolonged survival. The work defines the killing mechanism of blue light on VC-based cancer therapy and provides a practical approach for promoting VC uptake. This light-assisted VC therapy is not only highly efficient for melanoma but also considerable for a broad clinical utility.

Highly biocompatible Ag nanocluster-reinforced wound dressing with long-term and synergistic bactericidal activity.

Clinical application of antibiotic-free agents like silver nanoparticle-derived materials remains a critical challenge due to their limited long-term antibacterial activity and potential system toxicity. Herein, a highly biocompatible Ag nanocluster-reinforced hydrogel with enhanced synergistic antibacterial ability has been developed. Specifically, bioactive curcumin was incorporated into lysozyme-protected ultrasmall Ag nanoclusters (LC-AgNCs) and further integrated with sodium alginate (Sa) hydrogel (LC-AgNCs@Sa) through multiple interaction forces. Due to the synergistic antibacterial activity, LC-AgNCs could effectively kill both S. aureus and E. coli bacteria with a concentration down to 2.5 µg mL-1. In-depth mechanism investigations revealed that the bactericidal effect of LC-AgNCs lies in their bacterial membrane destruction, reactive oxygen species (ROS) production, glutathione depletion and prooxidant-antioxidant system disruption ability. Curcumin can mediate the intracellular ROS balance to protect NIH 3T3 cells from oxidative stress and improve the biocompatibility of LC-AgNCs@Sa. LC-AgNCs@Sa with long-term antibacterial ability can effectively protect the wound from bacterial invasion in vivo, and significantly accelerate the wound healing process due to their distinctive functions of inhibiting inflammatory factor (TNF-α) production, promoting collagen deposit and facilitating re-epithelization. This study provides a new, versatile strategy for the design of high-performance antibacterial dressing for broad infectious disease therapy.

A Manganese-Based Metal-Organic Framework as a Cold-Adapted Nanozyme.

The development of cold-adapted enzymes with high efficiency and good stability is an advanced strategy to overcome the limitations of catalytic medicine in low and cryogenic temperatures. In this work, inspired by natural enzymes, a novel cold-adapted nanozyme based on a manganese-based nanosized metal-organic framework (nMnBTC) is designed and synthesized. The nMnBTC as an oxidase mimetic not only exhibits excellent activity at 0 °C, but also presents almost no observable activity loss as the temperature is increased to 45 °C. This breaks the traditional recognition that enzymes show maximum activity only under specific psychrophilic or thermophilic condition. The superior performance of nMnBTC as a cold-adapted nanozyme can be attributed to its high-catalytic efficiency at low temperature, good substrate affinity, and flexible conformation. Based on the robust performance of nMnBTC, a low-temperature antiviral strategy is developed to inactivate influenza virus H1N1 even at -20 °C. These results not only provide an important guide for the rational design of highly efficient artificial cold-adapted enzymes, but also pave a novel way for biomedical application in cryogenic fields.

A Novel Fluoro-Pyrazine-Bridged Donor-Accepter-Donor Fluorescent Probe for Lipid Droplet-Specific Imaging in Diverse Cells and Superoxide Anion Generation.

PURPOSE: Lipid droplets (LDs) are dynamic organelles which associated with many metabolic processes. Reliable long-term imaging of LD is of great importance in LD-based therapy and research. Conventional fluorescent probes suffer from poor photostability and difficulty of preparation, which compromise their LD imaging ability. In this study, we aim to provide a novel and universal fluorescent probe for LD-specific imaging in both eukaryotic and prokaryotic cells. The versatile and potential applications of the probe were also evaluated. METHODS: We used one-step Suzuki coupling reaction to synthesize a fluoro-pyrazine-bridged donor-acceptor-donor fluorescent probe (T-FP-T). The fluorescent properties and stability of T-FP-T were detected. Then, LD-specific imaging and dynamic movement tracking capabilities of T-FP-T were studied in fungus, bacteria, plant and animal tissues. The biosafety and photodynamic toxicity of the probe under different light irradiation were characterized. RESULTS: T-FP-T showed large Stokes shift, superior brightness, excellent photostability, low toxicity. T-FP-T exhibited significant overlaps with adipophilin antibody or the commercial LD probe (LipidSpot™) in the cytoplasm, but not with Mitotracker red, Lysotracker red and Peroxisome Labeling dye. Moreover, T-FP-T also showed efficient superoxide anion generation capability under white LED light irradiation. The viability of Hela cells co-treated with T-FP-T and 1-h white LED light irradiation decreased to 62%. CONCLUSIONS: All these outstanding capabilities make T-FP-T a new efficient LD-specific imaging probe. The generated superoxide anion from T-FP-T under white LED light irradiation could cause obvious cell death, which will inspire broad study in LD-targeted photodynamic therapy.

Highly flexible elastomer microfluidic chip for single cell manipulation.

New materials and fabrication technologies have significantly boosted the development of lab-on-a-chip technologies and functionalities. In this work, we developed a highly flexible elastomer microfluidic chip with a microchannel with a minimum width of ∼5 µm manufactured by imprinting onto an SU-8 template. We found that the deformation induced in the microstructures by manual stretching of the chip is higher than that for the chip itself, which we attribute to the stress concentration of microstructures. Here, we demonstrate that the elastomer enables the manipulation of single cells, such as dynamic trapping-releasing operations, by simply stretching and releasing the elastomer chip.

Ferrihydrite nanoparticles as the photosensitizer augment microbial infected wound healing with blue light.

Visible blue light exerts microbicidal effects with reduced deleterious effects compared with UV light. However, the lack of specific photosensitizers restricts the use of blue light on wound tissues. Here, we report the use of biomimetic ferrihydrite nanoparticles (Fhn) as the sensitizer to augment not only the antimicrobial but also the healing effects of blue light on S. aureus-infected wound tissue. Based on the excellent photo-Fenton active Fhn under blue light illumination (450 nm, 35 630 lux), the Fhn-sensitized blue-light therapy completely cured acute wound within 7 days in sessions of one hour per day and diminished bacterial and fungal colony-forming units more than 5 log (99.999%) and 2 log (99%) in vitro. Mechanistic studies revealed that hydroxyl radicals (˙OH) generated by the combined therapy could effectively damage the microbe genome and membranes without significant damage to wound tissues. Interestingly, these two naturally occurring nonantibiotic modalities (Fhn with blue light) significantly stimulate the angiogenesis and decrease the inflammatory response on the wound site, which accelerates the wound healing synergically. The results demonstrated the use of biomimetic Fhn as the general photosensitizer for enhanced antimicrobial, anti-inflammatory and wound healing effects of blue light-based therapy.

Biomedical Applications of Chinese Herb-Synthesized Silver Nanoparticles by Phytonanotechnology.

Recent advances in nanotechnology have opened up new avenues for the controlled synthesis of nanoparticles for biomedical and pharmaceutical applications. Chinese herbal medicine is a natural gift to humanity, and it has long been used as an antibacterial and anticancer agent. This study will highlight recent developments in the phytonanotechnological synthesis of Chinese herbal medicines to utilize their bioactive components in biomedical and therapeutic applications. Biologically synthesized silver nanoparticles (AgNPs) have emerged as a promising alternative to chemical and physical approaches for various biomedical applications. The comprehensive rationale of combinational or synergistic effects of Chinese herb-based AgNPs synthesis was investigated with superior physicochemical and biological properties, and their biomedical applications, including antimicrobial and anticancer activity and wound healing properties. AgNPs can damage the cell ultrastructure by triggering apoptosis, which includes the formation of reactive oxygen species (ROS), DNA disintegration, protein inactivation, and the regulation of various signaling pathways. However, the anticancer mechanism of Chinese herbal medicine-based AgNPs is more complicated due to the potential toxicity of AgNPs. Further in-depth studies are required to address Chinese herbs' various bioactive components and AgNPs as a synergistic approach to combat antimicrobial resistance, therapeutic efficiency of drug delivery, and control and prevention of newly emerged diseases.

Self-Assembly of an Antitumor Dipeptide Induced Near-Infrared Fluorescence and Improved Stability for Theranostic Applications.

It has been found that the self-assembly of nonfluorescent peptides can generate fluorescent peptide nanoparticles (f-PNPs) to perform multiple functions, including drug delivery and imaging and tracking therapeutic agents. Both pharmacologically inactive peptides and tumor-targeting peptides have been explored to construct biocompatible f-PNPs; however, the application of this technology in delivering antitumor peptides has never been reported. Herein, the self-assembly of an antitumor dipeptide, carnosine, into fluorescent carnosine nanoparticles (f-Car NPs) in the presence of zinc ions is demonstrated. The generated f-Car NPs exhibit fluorescence in the visible and near-infrared (NIR) ranges for fluorescence tracing in vitro and in vivo. On the other hand, the f-Car NPs minimize the contact between the dipeptide and the serum, which overcomes the dipeptide instability resulted from inefficient antitumor activity. In addition, the preparation of f-Car NPs does not introduce extra carrier materials, so the f-Car NPs exhibit biocompatibility to normal fibroblast cells in vitro and negligible toxicity against major organs in vivo. This study provides a new peptide drug delivery strategy with NIR fluorescence tracing ability.

Blue light-triggered Fe2+-release from monodispersed ferrihydrite nanoparticles for cancer iron therapy.

Site-specific Fe2+ generation is promising for tumor therapy. Up to now, reported materials or systems for Fe2+ delivery do not naturally exist in the body, and their biological safety and toxicity are concerned. Herein, inspired by the natural biomineral ferrihydrite in ferritin, we synthesized monodispersed ferrihydrite nanoparticles and demonstrated a light triggered Fe2+ generation on tumor sites. Ferrihydrite nanoparticles of 20-30 nm in diameter possessed high cellular uptake efficiency and good biocompatibility. Under common blue light illumination, a large amount of Fe2+ could be released from ferrihydrite and promote the iron/reactive oxygen species (ROS)-related irreversible DNA fragmentation and glutathione peroxidase 4 (GPX4) inhibition, which led to the apoptosis- and ferroptosis-depended cancer cell proliferation inhibition. On mice, this method induced tumor associated macrophage (TAM) polarization from the tumor-promoting M2 type to the tumor-killing M1 type. With the intravenous pre-injection of ferrihydrite, the combinational effects of the light/Fe2+-approach attenuated pulmonary metastasis on mice. These results demonstrated a novel external light controlled Fe2+-generation approach based on biomineral, which will fully tap the anti-cancer potential of Fe2+ in chemo-dynamic, photo-dynamic and immune-activating therapies.

Single-Point Mutant Inverts the Stereoselectivity of a Carbonyl Reductase toward ß-Ketoesters with Enhanced Activity.

Enzyme stereoselectivity control is still a major challenge. To gain insight into the molecular basis of enzyme stereo-recognition and expand the source of antiPrelog carbonyl reductase toward ß-ketoesters, rational enzyme design aiming at stereoselectivity inversion was performed. The designed variant Q139G switched the enzyme stereoselectivity toward ß-ketoesters from Prelog to antiPrelog, providing corresponding alcohols in high enantiomeric purity (89.1-99.1 % ee). More importantly, the well-known trade-off between stereoselectivity and activity was not found. Q139G exhibited higher catalytic activity than the wildtype enzyme, the enhancement of the catalytic efficiency (kcat /Km ) varied from 1.1- to 27.1-fold. Interestingly, the mutant Q139G did not lead to reversed stereoselectivity toward aromatic ketones. Analysis of enzyme-substrate complexes showed that the structural flexibility of ß-ketoesters and a newly formed cave together facilitated the formation of the antiPrelog-preferred conformation. In contrast, the relatively large and rigid structure of the aromatic ketones prevents them from forming the antiPrelog-preferred conformation.

Persistent luminescence-polypyrrole nanocomposite for dual-modal imaging and photothermal therapy of mammary cancer.

Multifunctional nanocomposites that possess imaging and high-performance therapeutic features are experiencing a surge in interest in the precision clinical anticancer treatment. In this work, we reported the fabrication and bio-application of a novel persistent luminescence-polypyrrole nanocomposite (LPLNP@SPP) for photoacoustic/persistent luminescence (PA/PL) dual-modal imaging guided photothermal therapy (PTT). The construction of LPLNP@SPP avoids the PL quenching of LPLNP-OH by the polypyrrole-coating, and thus enables the combination of PL and PTT. The LPLNP@SPP shows excellent biocompatibility, long lasting near-infrared (NIR) PL emitting without in situ excitation and high-contrast PA signals. Meanwhile, this nanocomposite exhibits strong NIR absorbance and exceptional photothermal conversion capability, which provides notable potential for imaging-guided antitumor therapy. Thus, our work highlights the dual-functional core-shell LPLNP@SPP as a feasible theranostic nanoplatform for cancer diagnosis and therapy.

Construct of Carbon Nanotube-Supported Fe2O3 Hybrid Nanozyme by Atomic Layer Deposition for Highly Efficient Dopamine Sensing.

The Fe2O3 nanozyme has been identified as the most promising alternative for the Fe3O4 nanozyme due to its relatively low toxic risk and good chemical stability. However, its enzyme-like activity is relatively low enough to meet specific application requirements. Furthermore, previous synthesis approaches have difficulties in fabricating ultra-small Fe2O3 nanoparticles with tunable size and suffer from agglomeration problems. In this study, atomic layer deposition (ALD) was used to deposit Fe2O3 on surfaces of carbon nanotubes to form hybrid nanozymes (Fe2O3/CNTs). ALD enables the preparation of ultrafine Fe2O3 nanoparticles with precise size control <1 nm, while CNTs could be served as promising support for good dispersibility and as an effective activity activator. Hence, the formed Fe2O3/CNTs exhibit excellent peroxidase-like activity with a specific peroxidase activity of 24.5 U mg-1. A colorimetric method for sensing dopamine (DA) was established and presented good sensitivity with a limit of detection (LOD) as low as 0.11 µM. These results demonstrated that, in virtue of meticulous engineering methods like ALD, carbon nanomaterial-based hybrids can be developed as talented enzyme mimetic, thus paving a way for nanozyme design with desired activity and broadening their applications in biosensing and other fields.

Persistent Luminescence Nanoplatform with Fenton-like Catalytic Activity for Tumor Multimodal Imaging and Photoenhanced Combination Therapy.

Reactive oxygen species-mediated tumor chemodynamic therapy and photodynamic therapy have captured extensive attention in practical cancer combination therapies. However, the severe treatment conditions and the hypoxic microenvironment of solid tumors significantly limit the efficacy of these therapies. This work demonstrates the design and fabrication of a multifunctional persistent luminescence nanoplatform (PHFI, refers to PLNP-HSA-Fe3+-IR780) for cancer multimodal imaging and effective photoenhanced combination therapy. The near-infrared-emitted persistent luminescence nanoparticles (PLNP) was modified with human serum albumin (HSA) combined with an IR780 probe and Fe3+. The synthesized PHFI possesses high longitudinal relaxivity, obvious photoacoustic contrast signals, and long-lasting persistent luminescence, indicating that PHFI can be used for cancer magnetic resonance imaging, photoacoustic imaging, and persistent luminescence multimodal imaging. PHFI shows intrinsic photoenhanced Fenton-like catalytic activities as well as photodynamic and photothermal effects and thereby can effectively overcome severe treatment conditions for killing tumor cells. It is worth noting that PHFI serving as a rechargeable internal light source for photoenhanced combination therapy was first disclosed. We believe that our work shows the great potential of PHFI for cancer theranostics and will advance the development of PLNP-based nanoplatforms in tumor catalytic therapy.

One step synthesis of positively charged gold nanoclusters as effective antimicrobial nanoagents against multidrug-resistant bacteria and biofilms.

Positively charged gold nanoclusters (AuNCs) hold great promises as novel nanoagents in many biomedical applications, but their controllable synthesis in a simple and efficient manner remains a challenge. In the present work, by using a commercial cationic ligand, (11-mercaptoundecyl) - N,N,N-trimethylammonium bromide (MUTAB), we demonstrated that water-soluble, positively charged AuNCs can be facilely synthesized in a one-step reaction. These MUTAB-AuNCs possess near-infrared luminescence, ultra-small size, good stability and biocompatibility as well as abundant positive charges in a wide pH range. Importantly, these positively charged MUTAB-AuNCs exhibit efficient antibacterial activity against both Gram-negative bacteria and Gram-positive bacteria without inducing drug-resistance, including multidrug-resistant (MDR) bacteria and clinical bacteria. The unique antibacterial mechanism of these positively charged AuNCs was also systematically investigated by different techniques, including surface plasmon resonance, scanning electron microscopy, fluorescence imaging, DNA leakage and reactive oxygen species (ROS) assays.

Recent Advances of Persistent Luminescence Nanoparticles in Bioapplications.

Persistent luminescence phosphors are a novel group of promising luminescent materials with afterglow properties after the stoppage of excitation. In the past decade, persistent luminescence nanoparticles (PLNPs) with intriguing optical properties have attracted a wide range of attention in various areas. Especially in recent years, the development and applications in biomedical fields have been widely explored. Owing to the efficient elimination of the autofluorescence interferences from biotissues and the ultra-long near-infrared afterglow emission, many researches have focused on the manipulation of PLNPs in biosensing, cell tracking, bioimaging and cancer therapy. These achievements stimulated the growing interest in designing new types of PLNPs with desired superior characteristics and multiple functions. In this review, we summarize the works on synthesis methods, bioapplications, biomembrane modification and biosafety of PLNPs and highlight the recent advances in biosensing, imaging and imaging-guided therapy. We further discuss the new types of PLNPs as a newly emerged class of functional biomaterials for multiple applications. Finally, the remaining problems and challenges are discussed with suggestions and prospects for potential future directions in the biomedical applications.