Covalent organic frameworks (COFs) are a class of crystalline porous polymer composed of organic units developed in recent years. Due to their good porosity, modularity, crystallinity and biocompatibility, they show a good application prospect in tumor therapy. The porous channels with adjustable pore sizes of COFs make them become an ideal drug delivery material. In addition, COFs can also be used in photothermal therapy and photodynamic therapy in combination with photothermal agents and photosensitizers. This review systematically introduces the synthesis methods of COFs, including solvothermal synthesis, mechanochemical synthesis, microwave synthesis, ionothermal synthesis, interfacial synthesis, room temperature synthesis and nanoscale synthesis. According to the differences in the mechanism of tumor therapy, the applications of COFs nanocarrier system for tumor therapy were reviewed, including chemotherapy, photothermal therapy, photodynamic therapy and combined therapy, proving that the promising drug carrier can effectively improve the therapeutic effect of nanocarriers on tumors. In addition, the main challenges and development trends of the COFs in the field of tumor therapy are discussed. This review could inspire research to design more effective COFs nano-drug delivery systems and promote the development of tumor therapy.

Developing biocompatible, multifunctional and in-situ labeling nanoplatform is high challenging for molecular imaging. Organic derivates melanin nanoparticles (MNPs) holds great potential to be multimodal contrast agents, and have been used for photoacoustic imaging, magnetic resonance imaging, and ⁶⁴Cu PET imaging with simple modifications. In order to extend MNPs application in molecular imaging, here a novel radio-nuclide was applied to in-situ labeling of MNPs. Large numbers of active dihydroxyindole/indolequinone groups and natural binding ability of MNPs enabled them to have the ability to label different types of radionuclides which have unique half-life and functions, especially long-life elemental nuclide. This project explored the in-situ labeling methods of organic melanin nanoparticles with a promising diagnostic radionuclides named Iodine-124 (¹²⁴I), and using this novel multifunctional organic nanoparticles for preliminary molecular imaging studies. Generally, ultrafine particle size melanin nanoparticles (5.5 nm in diameter) were prepared by ultrasonication method using naturally occurring melanin, then PEG₃₅₀₀ which had amino group at both ends was used as a stabilizer agent to obtain PEG-MNP nanocarriers (7.5 nm in diameter) with better water solubility and stability. The nanoparticles were full characterized by dynamic light scattering (DLS), transmission electron microscope (TEM) and ¹H NMR, respectively. Then, one kind of elemental nuclide was labeled. Classic iodine labeled method with N-Bromo Succinimide (NBS) was used as oxidant to oxidize active dihydroxyindole/indolequinone ring of PEG-MNP for electrophilic substitution reaction labeling ¹²⁴I (100.8 h). This reaction rate is extremely fast (60 s reaction time) and high labelling yield (>99%). The ¹²⁴I was labeled successfully and in-situ labeled PEG-MNP nanocarriers were obtained. After that, ¹²⁴I and ¹²⁴I-PEG-MNP were used to further preclinical evaluation by micro-PET imaging. Micro-PET images were collected at 2 h, 24 h and 48 h after intravenous injection 7.4 MBq ¹²⁴I and ¹²⁴I-PEG-MNP in normal Kunming mice (n=3). The ROI target area of heart, liver and thyroid were delineated for semi-quantitative analysis. Then, in order to verify the imaging ability of ¹²⁴I-PEG-MNP in solid tumor. We built human pancreatic cancer BxPC3 xenograft model (n=3), and Micro-PET scans were performed at different time points. Results showed that the labeling rate of ¹²⁴I on PEG-MNP was 99.9%. And the radiochemical purity in vitro stability of ¹²⁴I-PEG-MNP in 96 h was more than 90%. Micro-PET images showed that ¹²⁴I-PEG-MNP had no obvious thyroid uptake which indicated no de-marking in mice. The radio-distribution of ¹²⁴I and ¹²⁴I-PEG-MNP was substantially different in liver and thyroid (P<0.001). In vivo semi-quantitative analysis showed that the radio uptakes of organs were consistent with the distribution of nanoparticles. And the PET imaging of xenograft mice showed that ¹²⁴I-PEG-MNP can utilize the enhanced permeability and retention effect (EPR) to be significantly enriched at the tumor and retained in the tumor site for more than 48 h. PEG-MNP has the ability to label long half-life nuclide ¹²⁴I. This research provides an experimental basis for further construction of long-circulation multimodal imaging probes.

Oral cancer is head and neck cancer, and cancer tissue is located in the oral cavity. The non-invasive early diagnosis is an effective method to reduce the death of the disease. The oral cancer-related substances are first released into the saliva, which is convenient, safe and non-invasive, and is the first choice for screening and early diagnosis of oral cancer. In this paper, the specific types and the commonly used detection methods of the salivary tumor biomarkers at home and abroad were summarized and compared. Specifically, the latest application of new electrochemical biosensor in the detection of the salivary tumor biomarkers associated with oral cancer was mainly described. Futhermore, the summary of its future directions and the potential applications was proposed, which provided reference for the further research and application of the salivary tumor biomarkers in oral cancer.

The tumor microenvironment with low pH and high-level glutathione is different from other issues, which provides more possible strategies for designing drug delivery systems (DDSs). In this manuscript, we designed a microenvironment-responsive Mn₃O₄/DOX@Lip nano-DDS. Mn₃O₄ nanoparticles were prepared by thermal decomposition. Based on coordination of the chemotherapy drug doxorubicin (DOX) with Mn atom, the Mn₃O₄ nanoparticles could load and deliver DOX. A layer of sensitive liposomes was assembled on the outermost layer to further effectively prevent the leakage of DOX during the delivery process. X-ray diffraction (XRD) and energy dispersive X-ray spectroscopy (EDX) analysis results showed the manganese oxide was Mn₃O₄. The morphology and particle size of Mn₃O₄ were characterized by transmission electron microscope (TEM) and dynamic light scattering (DLS). Results showed that the Mn₃O₄ nanoparticles were a relatively uniform polyhedron with a particle size of around 20 nm. The drug loading of particles was 100 μg/mg. In weakly acidic microenvironment of tumor cells, the liposome membrane ruptured. In addition, the high-level glutathione microenvironment was also conducive to the decomposition of Mn ₃O₄ and the DOX was released in cells. Confocal imaging results demonstrated that after co-incubation with the Mn₃O₄ particles, the fluorescence of reactive oxygen species (ROS) probe in cancer cells increased significantly, indicating that the DDS could trigger an increase of ROS in cells by down-regulating the content of glutathione. The amount of ROS depended on the concentration of added particles and the incubation time. MTT and flow cytometry experiment results showed that Mn₃O₄/DOX@Lip had more cell cytotoxic compared to the single chemotherapy drug. It might be ascribed to the Fenton-like reaction triggered by the reduction product Mn²⁺, which converted the H₂O₂ in the cell into the more toxic •OH and promoted apoptosis. The ROS-mediated apoptosis and chemotherapy played a synergistic effect to enhance the ability of cell apoptosis. This proposed Mn ₃O₄/DOX@Lip nano-DDS uses exogenous substances to stimulate endogenous cytotoxicity and enhance the effect of chemotherapy drug, providing new research strategies for tumor treatment.

The biomedical applications of fluorescence/photoacoustic imaging and phototherapy have attracted more and more attention. However, many fluorescent/photoacoustic contrast agents have some common problems, such as poor biocompatibility, lack of tumor targeting, low signal-to-noise ratio, single function and so on, which seriously limit their application in diagnosis and treatment. Hyaluronic acid (HA) exhibits excellent biocompatibility and active tumor targeting, can be degraded by hyaluronidase, and is easy to be chemically modified and realize the cooperation of a variety of supramolecular weak interactions. Therefore, HA has been combined with fluorescent/photoacoustic contrast agents to prepare nanomaterials, which greatly improves the labeling performance and therapeutic effects in cells and even in vivo. In this paper, the preparation methods of nanomaterials by combining these two kinds of materials are reviewed, and the relationships between the structure and performance of nanomaterials are emphasized, which provides guidance for their future design and development. Finally, the main problems and important research directions in the future are analyzed and prospected.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory loss, confusion, and a variety of cognitive disabilities. The self-assembly and aggregation of β-amyloid (Aβ) peptides is a main feature of the brain of Alzheimer's disease, which can aggravate the nerve damage and cognitive impairment of AD patients. Therefore, inhibition of the aggregation of Aβ peptides is recognized as a potential strategy to alleviate AD. Photodynamic therapy (PDT) is a creative method that has wide applications in suppressing amyloid aggregation or eliminating the amyloid aggregates. However, most photosensitizers are excited by ultraviolet and visible light, have a low penetration depth in biological tissues, and cause serious tissue damage, which limits their application in biomedicine. Herein, we report a dual-targeting upconversion nanoprobe excited by near-infrared light to inhibit the Aβ aggregation process. The core-shell structured upconversion nanoparticles NaYF₄:Yb,Er,Gd,Tm@NaYF₄ are used as light converters, and the photosensitizer chlorin-e6 (Ce6) is loaded through the hydrophobic coating of the amphiphilic polymer 1,2-distearoylsn-glycero-3-phosphoethanolamine-N- [maleimide(polyethyleneglycol)-2000] (DSPE-PEG-MAL). A blood-brain barrier targeting peptide, TGN, and a Aβ target peptide, QSH, are simultaneously modified on the surface of nanoparticles via the specific reaction between maleimide and sulfhydryl groups. The results indicate that UCNPs can transfer the excited-state energy to the photosensitizer Ce6 through luminescence resonance energy transfer (LRET) process under the excitation of near-infrared light irradiation. After transition to the excited state, Ce6 further interact with the surrounding oxygen molecules to produce singlet oxygen (¹O₂) and irreversibly oxidize β-amyloid, thus effectively disassembling Aβ aggregates and reducing the cytotoxicity associated with Aβ. In addition, UCNPs-Ce6-TQ not only exhibits good biocompatibility, but also can effectively cross the blood-brain barrier and target Aβ₄₂. This nanoprobe may be a powerful tool to inhibit the accumulation of Aβ in the brain and alleviate the neurotoxic damage caused by Aβ.

Cancer is a major cause of death and its early diagnosis has been a research goal for many decades. For males, prostatic carcinoma has become the second leading cause of cancer death worldwide. Prostate specific membrane antigen (PSMA) has been widely recognized as a prostate cancer marker. Thus, measurement of PSMA would be more valuable for the early diagnosis of prostate cancer. Nanomaterials have the characteristics of small size effect, quantum size effect, macroscopic quantum tunneling effect and surface effect, and have been widely used in various fields, such as cell imaging, analysis and detection, drug release and treatment. Gold nanoparticles have been widely used in biosensing and medical diagnosis due to their simple preparation, high stability and unique photoelectric properties. In this paper, a new colorimetric approach is proposed for simple detection of PSMA based on gold nanoparticles. In the experiment, we synthesized gold nanoparticles with positive charges, and the polyanionic peptide as the substrate of PSMA. The detection of PSMA was based on the property that different aggregation states of gold nanoparticles can lead to the change of color and the specific recognition of PSMA for its substrate. The positively charged gold nanoparticles interact electrostatically with polyanionic peptide, resulting in aggregation of gold nanoparticles. In the presence of PSMA, however, the polyanionic peptide are hydrolyzed into glutamic acid fragment due to the reaction between the PSMA and the polyanionic peptide, resulting in the dispersion of gold nanoparticles. This behaviour leads to the development of a rapid and simple colorimetric method for assaying PSMA activity, with a detection limit of 0.5 nmol/L and the linear range of 2~10 nmol/L. This approach is simple compared to the existing ones since the gold nanoparticles-peptide based sensor is easy to be assembled and the detection can be achieved without the involvement of complicated procedures. Moreover, the applicability of the method has been demonstrated by detecting PSMA spiked into urine samples.

Protein glycosylation occurs during and after the translation process, and glycosylation will diversify the function of the protein. Glycosylation directly or indirectly affects the function of proteins and their interactions, and is related to a variety of human diseases. Among them, sialylated N-glycans play a key role in many important physiological and pathological processes. Sialic acid usually bonds with adjacent monosaccharides via α-2,3-, α-2,6-, α-2,8- or α-2,9- linkage. Sialylated N-glycans with different linkage always have different functions in cell activities, physiological and pathological processes of living organisms. Mass spectrometry is an important tool for the analysis of N-glycans. It can quickly and sensitively detect N-glycans. The separation and detection of sialylated N-glycans and their linked isomers can be achieved by combining chromatographic techniques and derivatization methods with mass spectrometry. In this review, we mainly focuses on α-2,3- and α-2,6-linked sialylated N-glycans, introduces their structure and different functions in cell activities and various diseases, and summarizes the analysis methods of linked isomers of sialylated N-glycans based on mass spectrometry and the application of these methods in the field of biomedicine in recent years. This review can provide new ideas and approaches for future biomedical research.

Macrocycles such as cyclodextrin and crown ether are applied to construct artificial transmembrane ion transport systems owing to their unique cavity structure and the ability to recognize molecules and ions via host-guest interaction. Compared with natural channel proteins, macrocycles have many advantages, such as the low cost, stabilities, easy structural modification and functionalization, etc., which make them preferable candidates for preparing artificial ion channel. Herein, we reviewed the recent progress of macrocycles-based artificial ion channels, and systematically summarized the preparation methods, structural regulation and potential applications of the artificial ion channels based on different macrocycles. Finally, we have briefly summarized and outlooked the progress of macrocycle-based artificial ion channels. This review is of great significance for developing novel artificial transmembrane ion channels and exploring their potential applications.

microRNA is an endogenous non-coding single-stranded RNA with a length of about 18~24 nucleotides. The latest research has found that the occurrence of many diseases and tumors is closely related to the level of microRNA expression, and microRNA is expected to become a new tumor marker and a new target for cancer treatment. Therefore, the development of high sensitivity, high specificity, and simple and rapid microRNA detection methods is greatly significant for biomedical research and early diagnosis of cancer. Surface-enhanced Raman spectroscopy (SERS) technique has great application value in the field of early cancer diagnosis due to its unique advantages such as high sensitivity, fast detection speed, fingerprint recognition, and low water interference. The latest research progress of SERS technique in microRNA detection is summarized in this review. Finally the main challenges of SERS technique in bioassay are discussed and the future development trend is proposed.

Injectable hydrogels, as an effective vehicle for localized drug delivery, have attracted increasing attention in recent years. With improved tumor-specific drug accumulation and lowered risk of infection, the application of in situ-forming injectable hydrogels provides an alternative to surgical implantation. In this study, based on a unique feature of regenerated silk fibroin (RSF) that it can easily form β-sheet structures, which function as physical cross-links, under various conditions, we designed an injectable silk fibroin hydrogel which encapsulated SBA-15 for the co-delivery of a vascular disrupting agent, combretastatin A4 disodium phosphate (CA4P), and doxorubicin hydrochloride (DOX). Such a CA4P and DOX co-encapsulated hydrogel ((RSF/CA4P)-(SBA-15/DOX)), simply prepared through a designed ultrasonication procedure, showed two different types of drug release behavior. CA4P was rapidly released, and it not only targeted the abnormal vasculature of tumors, causing vascular collapse, but also inhibited tumor cell proliferation by binding to tubulin and arresting mitosis. On the other hand, the sustained release of DOX can inhibit the proliferation of tumor cells for a prolonged period of time. Because of the rapid disruption of tumor vasculature and sustained inhibition of tumor cells proliferation, the (RSF/CA4P)-(SBA-15/DOX) hydrogel showed significantly enhanced cytotoxicity against human breast carcinoma cells (MDA-MB-231). By using this co-delivery system, the required dose of DOX can be lowered, and at the same time, the superior antitumor efficacy of the drugs is maintained. Our results suggest that the application of silk fibroin hydrogels to the co-delivery of a vascular disrupting agent and a chemotherapeutic agent with different drug release behaviors is a promising strategy in tumor treatment. Moreover, after sonication, the hydrogel precursor of (RSF/CA4P)-(SBA-15/DOX), can reach target irregular-shaped tumor sites via intratumor injection, and the hydrogels then form in situ, simply induced by body heat. Such silk fibroin-based hydrogels are injectable and malleable and fluorescent in dark field, which greatly facilitates their biomedical applications.