Dual roles of HK3 in regulating the network between tumor cells and tumor-associated macrophages in neuroblastoma.

Neuroblastoma (NB) is the most common and deadliest extracranial solid tumor in children. Targeting tumor-associated macrophages (TAMs) is a strategy for attenuating tumor-promoting states. The crosstalk between cancer cells and TAMs plays a pivotal role in mediating tumor progression in NB. The overexpression of Hexokinase-3 (HK3), a pivotal enzyme in glucose metabolism, has been associated with poor prognosis in NB patients. Furthermore, it correlates with the infiltration of M2-like macrophages within NB tumors, indicating its significant involvement in tumor progression. Therefore, HK3 not only directly regulates the malignant biological behaviors of tumor cells, such as proliferation, migration, and invasion, but also recruits and polarizes M2-like macrophages through the PI3K/AKT-CXCL14 axis in neuroblastoma. The secretion of lactate and histone lactylation alterations within tumor cells accompanies this interaction. Additionally, elevated expression of HK3 in M2-TAMs was found at the same time. Modulating HK3 within M2-TAMs alters the biological behavior of tumor cells, as demonstrated by our in vitro studies. This study highlights the pivotal role of HK3 in the progression of NB malignancy and its intricate regulatory network with M2-TAMs. It establishes HK3 as a promising dual-functional biomarker and therapeutic target in combating neuroblastoma.

Principal component analysis-assisted zirconium-based metal-organic frameworks/DNA biosensor for the analysis of various phosphates.

Considering the diversity of phosphates and their pivotal roles in physiological processes, detection of various phosphates related to their metabolism is urgent but challenging. Herein, we design a biosensor with zirconium-based MOFs (Zr-MOFs) and fluorophore-modified single-stranded DNA (F-ssDNA) for the analysis of phosphates. Relying on the interaction between Zr clusters and phosphate backbone, F-ssDNA is anchored on the surface of Zr-MOFs, inducing fluorescence resonance energy transfer (FRET) and subsequently quenching the fluorescence of F-ssDNA. Meanwhile, phosphates with different numbers of phosphate groups, molecular structures and coordination environments are able to adjust the FRET between Zr-MOFs and F-ssDNA via a site-occupying effect, recovering the fluorescence of F-ssDNA in distinct cases, which may result in diverse fluorescence signals. Consequently, seventeen phosphates and four phosphate mixtures are discriminated with the assistance of principal component analysis. These results provide new insight into the application of Zr-MOFs and broaden the path for the development of analytical methods for phosphates.

Polarity Conversion of the Ag2S/AgInS2 Heterojunction by Radical-Induced Positive Feedback Polydopamine Adhesion for Signal-Switchable Photoelectrochemical Biosensing.

Efficient tuning of the polarity of photoactive nanomaterials is of great importance in improving the performance of photoelectrochemical (PEC) sensing platforms. Herein, polarity of the Ag2S/AgInS2 heterojunction is converted by radical-induced positive feedback polydopamine (PDA) adhesion, which is further employed to develop a signal-switchable PEC biosensor. In the nanocomposites, Ag2S and AgInS2 achieve electron-hole separation, exhibiting a strong anodic PEC response. Under the irradiation of light, the Ag2S/AgInS2 heterojunction is able to produce superoxide radical and hydroxyl radical intermediate species, leading to the polymerization of dopamine (DA) and the subsequent adhesion of PDA onto the Ag2S/AgInS2 heterojunction (Ag2S/AgInS2@PDA). By constructing a new electron-transfer pathway with PDA, the polarity of the Ag2S/AgInS2 heterojunction is converted, and the PEC response changes from anodic to cathodic photocurrents. In addition, since the photoreduction activity of PDA is stronger than that of the Ag2S/AgInS2 heterojunction, more superoxide radical can be produced by Ag2S/AgInS2@PDA once PDA is generated, thereby promoting the generation of PDA. Consequently, a positive feedback mechanism is established to enhance the polarity conversion of the Ag2S/AgInS2 heterojunction and amplify the responding to DA. As a result, the bioanalytical method is capable of sensitively quantifying DA in 10 orders of magnitude with an ultralow limit of detection. Moreover, the applicability of this biosensor in real samples is identified by measuring DA in fetal bovine serum and compared with a commercial ELISA method. Overall, this work offers an alternative perspective for adjusting photogenerated carriers of nanomaterials and designing high-performance PEC biosensors.

A microtubule stabilizer ameliorates protein pathogenesis and neurodegeneration in mouse models of repetitive traumatic brain injury.

Tau pathogenesis is a hallmark of many neurodegenerative diseases, including Alzheimer's disease (AD). Although the events leading to initial tau misfolding and subsequent tau spreading in patient brains are largely unknown, traumatic brain injury (TBI) may be a risk factor for tau-mediated neurodegeneration. Using a repetitive TBI (rTBI) paradigm, we report that rTBI induced somatic accumulation of phosphorylated and misfolded tau, as well as neurodegeneration across multiple brain areas in 7-month-old tau transgenic PS19 mice but not wild-type (WT) mice. rTBI accelerated somatic tau pathology in younger PS19 mice and WT mice only after inoculation with tau preformed fibrils and AD brain-derived pathological tau (AD-tau), respectively, suggesting that tau seeds are needed for rTBI-induced somatic tau pathology. rTBI further disrupted axonal microtubules and induced punctate tau and TAR DNA binding protein 43 (TDP-43) pathology in the optic tracts of WT mice. These changes in the optic tract were associated with a decline of visual function. Treatment with a brain-penetrant microtubule-stabilizing molecule reduced rTBI-induced tau, TDP-43 pathogenesis, and neurodegeneration in the optic tract as well as visual dysfunction. Treatment with the microtubule stabilizer also alleviated rTBI-induced tau pathology in the cortices of AD-tau-inoculated WT mice. These results indicate that rTBI facilitates abnormal microtubule organization, pathological tau formation, and neurodegeneration and suggest microtubule stabilization as a potential therapeutic avenue for TBI-induced neurodegeneration.

Homotypic Membrane-Enhanced Blood-Brain Barrier Crossing and Glioblastoma Targeting for Precise Surgical Resection and Photothermal Therapy.

The crossing of blood-brain barrier (BBB) is essential for glioblastoma (GBM) therapy, and homotypic targeting is an effective strategy to achieve BBB crossing. In this work, GBM patient-derived tumor cell membrane (GBM-PDTCM) is prepared to cloak gold nanorods (AuNRs). Relying on the high homology of the GBM-PDTCM to the brain cell membrane, GBM-PDTCM@AuNRs realize efficient BBB crossing and selective GBM targeting. Meanwhile, owing to the functionalization of Raman reporter and lipophilic fluorophore, GBM-PDTCM@AuNRs are able to generate fluorescence and Raman signals at GBM lesion, and almost all tumor can be precisely resected in 15 min by the guidance of dual signals, ameliorating the surgical treatment for advanced GBM. In addition, photothermal therapy for orthotopic xenograft mice is accomplished by intravenous injection of GBM-PDTCM@AuNRs, doubling the median survival time of the mice, which improves the nonsurgical treatment for early GBM. Therefore, benefiting from homotypic membrane-enhanced BBB crossing and GBM targeting, all-stage GBM can be treated with GBM-PDTCM@AuNRs in distinct ways, providing an alternative idea for the therapy of tumor in the brain.

Activating NO-sGC crosstalk in the mouse vascular niche promotes vascular integrity and mitigates acute lung injury.

Disruption of endothelial cell (ECs) and pericytes interactions results in vascular leakage in acute lung injury (ALI). However, molecular signals mediating EC-pericyte crosstalk have not been systemically investigated, and whether targeting such crosstalk could be adopted to combat ALI remains elusive. Using comparative genome-wide EC-pericyte crosstalk analysis of healthy and LPS-challenged lungs, we discovered that crosstalk between endothelial nitric oxide and pericyte soluble guanylate cyclase (NO-sGC) is impaired in ALI. Indeed, stimulating the NO-sGC pathway promotes vascular integrity and reduces lung edema and inflammation-induced lung injury, while pericyte-specific sGC knockout abolishes this protective effect. Mechanistically, sGC activation suppresses cytoskeleton rearrangement in pericytes through inhibiting VASP-dependent F-actin formation and MRTFA/SRF-dependent de novo synthesis of genes associated with cytoskeleton rearrangement, thereby leading to the stabilization of EC-pericyte interactions. Collectively, our data demonstrate that impaired NO-sGC crosstalk in the vascular niche results in elevated vascular permeability, and pharmacological activation of this crosstalk represents a promising translational therapy for ALI.

Recent advances in electron manipulation of nanomaterials for photoelectrochemical biosensors.

Photoelectrochemical (PEC) biosensing as a promising and largely developing technique has been widely applied in biological analysis in recent years because of its low background signal and high sensitivity. By utilizing suitable PEC active materials to establish a photoelectric (PE) conversion system, selective and sensitive measurements can be achieved with the help of specific biological recognition elements. PEC biosensors rely on the change of photocurrent that depends on the electron transfer process of nanomaterials. Therefore, the electron manipulation of PEC active nanomaterials is crucial for PEC sensing. In this review, from the perspective of the electron transfer manipulation of PEC active nanomaterials, we summarize the principle of PEC biosensors in three parts, i.e., generation of excited electrons in PEC active materials, introduction of specific materials for the formation of new electron transfer pathways, and separation of excited electrons in semiconductors. For each part, typical PEC biosensors are displayed and compared to reveal the superiority of different principles. In addition, current challenges of PEC biosensors are discussed, and some insight is given into the development of PEC biosensors in the future.

Chemical Mechanism-Dominated and Reporter-Tunable Surface-Enhanced Raman Scattering via Directional Supramolecular Assembly.

Molecular resonance can be strengthened by charge transfer, profiting chemical mechanism (CM)-related surface-enhanced Raman scattering (SERS). Herein a supramolecular assembly enabled SERS system is established by functionalizing para-sulfonatocalix[4]arene (pSC4) onto Au3Cu nanocrystals (NCs). Due to the cooperation of Au and Cu, pSC4 is directionally assembled on the surface of Au3Cu NCs via van der Waals force, enabling photoinduced and hydrogen bond-induced charge transfer, which remarkably enhances the Raman scattering of methylene blue (MB) captured by pSC4. In particular, for the C-N and C-C stretching of MB, the contributions of resonance Raman scattering increase up to 80%. In addition, the SERS system is able to display affinities of different host-guest interactions, and further employed to evaluate effects of drugs for Alzheimer's disease. In this work, charge transfer is realized by performing supramolecular assembly on the surface of plasmonic nanomaterials, providing an avenue to design CM-related and reporter-tunable SERS systems.

Dual signal magnification for ultrasensitive biosensing based on well-regulated SERS of AuNTs@AuHg and DSN-assisted amplification.

AuNTs@AuHg alloy with well-regulated SERS properties was proposed, which displayed wonderful SERS intensity and effective salt resistance. Using miRNA-21 as a model analyte and combining with DSN-assisted amplification, a dual signal amplification strategy for ultrasensitive miRNA biosensing with a low detection limit (0.53 fM) and satisfactory selectivity was designed.

The Significance of PAX8-PPARγ Expression in Thyroid Cancer and the Application of a PAX8-PPARγ-Targeted Ultrasound Contrast Agent in the Early Diagnosis of Thyroid Cancer.

Objective: To investigate the significance of PAX8-PPARγ expression in thyroid cancer and the application of a PAX8-PPARγ-targeted ultrasound contrast agent in the early diagnosis of thyroid cancer. Methods: In this study, the expression of PAX8-PPARγ in thyroid cancer tissues, paracancer groups, and normal thyroid tissues was detected by western and immunohistochemical techniques; the effects of PAX8-PPARγ expression inhibition on thyroid cancer cell growth, clonogenic ability, and antiapoptosis were examined. The terminal carboxylactic acid/hydroxyacetic acid copolymer (PLGA-COOH) nanoparticles were prepared by the double emulsification solvent volatilization method. The in vitro cytotoxicity of the targeted contrast agent was detected by MTS and other methods; LD50 was used to evaluate its short-term in vivo toxicity after intraperitoneal injection in mice. Results: PAX8-PPARγ expression was significantly increased in thyroid cancer tissues, and the expression level of PAX8-PPARγ was closely correlated with TNM staging and lymph node metastasis (P < 0.05). In addition, PAX8-PPARγ was also expressed at high levels in thyroid cancer cell lines relative to normal thyroid cells. MTS experiments showed that the PAX8-PPARγ-targeted ultrasound nanocontrast agent had no significant toxic side effects on thyroid cells; countess observed that the contrast agent had no effect on cell survival and mortality; the LD50 assay showed that the targeted contrast agent had a wide safety range. Western blot showed the expression of caspase-3, BAX, and Bcl-2 in thyroid cancer cells, indicating that the nanocontrast agent has a good biosafety. In vitro targeting experiments showed that there were more nanospheres aggregated around the cells in the targeted contrast group. In vivo targeting imaging of nude mice revealed that the ultrasound signal was significantly enhanced in the targeted group compared with the nontargeted group after 20 min of LIFU irradiation. Conclusion: PAX8-PPARγ overexpression in thyroid cancer cell lines and thyroid cancer tissues promoted the proliferation and antiapoptotic ability of thyroid cancer cells and promoted the tumorigenic ability in nude mice in vivo. We successfully prepared a PAX8-PPARγ-targeted ultrasound nanocontrast agent, which has regular morphology, uniform size, and high stability, and its liquid-gas phase change can be promoted at lower temperature. Therefore, this contrast agent can achieve US-targeted imaging and temperature phase transition function, and may have enhanced ultrasound imaging potential.

Analysis on the Effects of CT- and Ultrasound-Guided Percutaneous Transthoracic Needle Biopsy Combined with Serum CA125 and CEA on the Diagnosis of Lung Cancer.

The number of patients with lung cancer is difficultly diagnosed in the early stage. The purpose of the study was to investigate the effects of CT- and ultrasound-guided percutaneous transthoracic needle biopsy combined with serum CA125 and CEA on the diagnosis of lung cancer. 120 patients with suspected lung cancer admitted to our hospital from January 2019 to January 2020 were selected and divided into an ultrasound group (n = 60) and CT group (n = 60), according to different percutaneous transthoracic needle biopsy modalities. All patients received serum tumor markers detection, so as to compare the CT- and ultrasound-guided percutaneous transthoracic needle biopsy results and pathology results, levels of serum tumor markers among all patients and the patients with different lung cancer types, and diagnostic efficacy of tumor markers, as well as complication rate (CR) in patients. The sensitivity and specificity of ultrasound-guided percutaneous transthoracic needle biopsy were 0.880 and 0.800, respectively, while those of CT-guided percutaneous transthoracic needle biopsy were 0.909 and 0.625, respectively; the CA125 and CEA levels in the lung cancer group were higher than those in the benign group (P < 0.001); the CA125 and CEA levels of the patients with adenocarcinoma were higher than those with squamous carcinoma, and the CEA levels of the patients with small-cell carcinoma were lower than those with adenocarcinoma (P < 0.05); the sensitivity, specificity, and Youden indexes of CA125 were 0.638, 0.833, and 0.471, respectively, while those of CEA were 0.766, 0.778, and 0.544, respectively; there were no significant differences in CR between the two groups (P > 0.05). CT- and ultrasound-guided percutaneous transthoracic needle biopsy is a safe and feasible diagnostic modality for lung cancer, and its combination with serum CA125 and CEA can significantly improve the accuracy of the detection results, which is worthy of promotion and application in clinical practice.

Enhancing Photoelectric Response of an Au@Ag/AgI Schottky Contact through Regulation of Localized Surface Plasmon Resonance.

Carrier generation and migration are both pivotal to photoelectric (PE) response. Formation of a Schottky contact is conducive to promote carrier migration but cannot fundamentally magnify carrier generation, limiting the eventual PE performance. In this work, an Au@Ag/AgI Schottky contact is established by in situ growth of AgI nanotriangles on the surface of Au@Ag nanoparticles (NPs), and PE enhancement of the Schottky contact is realized by regulating localized surface plasmon resonance (LSPR) properties. In comparison with Ag/AgI Schottky contact, assembly of Au NPs in the center of Ag NPs adjusts the dominated LSPR property from hot-electron transfer (HET) to plasmon-induced resonance energy transfer (PIRET). With the concurrent manipulation of HET and PIRET, additional energy can be employed for carrier generation, while photogenerated electrons offset by hot electrons are reduced, which jointly enlarges PE responses of the Au@Ag/AgI Schottky contact up to 4 times. Benefitted from the etching of thiols to Ag-based materials, the Au@Ag/AgI Schottky contact is further applied to the construction of a photoelectrochemical cysteine sensor. This work proposes a general strategy to enhance PE responses of Schottky contacts, which may advance the design of LSPR-related PE systems.

Discovery of a cooperative mode of inhibiting RIPK1 kinase.

RIPK1, a death domain-containing kinase, has been recognized as an important therapeutic target for inhibiting apoptosis, necroptosis, and inflammation under pathological conditions. RIPK1 kinase inhibitors have been advanced into clinical studies for the treatment of various human diseases. One of the current bottlenecks in developing RIPK1 inhibitors is to discover new approaches to inhibit this kinase as only limited chemotypes have been developed. Here we describe Necrostatin-34 (Nec-34), a small molecule that inhibits RIPK1 kinase with a mechanism distinct from known RIPK1 inhibitors such as Nec-1s. Mechanistic studies suggest that Nec-34 stabilizes RIPK1 kinase in an inactive conformation by occupying a distinct binding pocket in the kinase domain. Furthermore, we show that Nec-34 series of compounds can synergize with Nec-1s to inhibit RIPK1 in vitro and in vivo. Thus, Nec-34 defines a new strategy to target RIPK1 kinase and provides a potential option of combinatorial therapy for RIPK1-mediated diseases.

A Simple and Efficient Method to Generate Dual Site-Specific Conjugation ADCs with Cysteine Residue and an Unnatural Amino Acid.

Antibody-drug conjugates (ADCs) are complex pharmaceutical molecules that combine monoclonal antibodies with biologically active drugs through chemical linkers. ADCs are designed to specifically kill disease cells by utilizing the target specificity of antibodies and the cytotoxicity of chemical drugs. However, the traditional ADCs were only applied to a few disease targets because of some limitations such as the huge molecular weight, the uncontrollable coupling reactions, and a single mechanism of action. Here we report a simple, one-pot, successive reaction method to produce dual payload conjugates with the site-specifically engineered cysteine and p-acetyl-phenylalanine using Herceptin (trastuzumab), an anti-HER2 antibody drug widely used for breast cancer treatment, as a tool molecule. This strategy enables antibodies to conjugate with two mechanistically distinct cytotoxic drugs through different functional groups sequentially, therefore, rendering the newly designed ADCs with functional diversity and the potential to overcome drug resistance and enhance the therapeutic efficacy.

Modulating Polarization of Perovskite-Based Heterostructures via In Situ Semiconductor Generation and Enzyme Catalysis for Signal-Switchable Photoelectrochemical Biosensing.

Polarization of photoactive materials in current photoelectric (PE) systems is difficult to be adjusted, and thus electron-transfer routes of these systems are unchangeable, which limits their performance in photoelectrochemical (PEC) analysis. Herein, we attempted to modulate the polarization of perovskite-based heterostructures by both in situ semiconductor generation and enzyme catalysis. Owing to their band alignments, Cs3Bi2Br9 quantum dots (QDs) and BiOBr are confirmed to construct a Z-scheme structure, leading to a large anodic photocurrent. In the presence of ascorbic acid 2-phosphate (AAP), BiPO4 is generated on the surface of the Cs3Bi2Br9 QDs/BiOBr heterostructure, reassigning energy bands of BiOBr. Accordingly, polarization of the photoactive materials is converted, and a new Z-scheme structure with a reversed electron-transfer route is constructed, which leads to an evident cathodic photocurrent. Furthermore, abundant electron donors can be obtained by catalyzing AAP with alkaline phosphatase (ALP). In this case, photogenerated holes in BiOBr are preferentially annihilated by electron donors, thereby blocking transfer of photogenerated electrons in the Cs3Bi2Br9 QDs/BiOBr/BiPO4 heterostructure. Consequently, a second polarization conversion is triggered by enzyme catalysis, resulting in the recovery of an anodic photocurrent. Benefited from the polarization conversion, a PEC biosensor with a feature of two-wing signal switch is designed, which remarkably enlarges the range of the signal response and subsequently improves the analytical performance. As a result, ALP in small volume of human serum can be quantified with this method. In this work, polarization of perovskite-based photoactive materials is tuned, proposing an alternative perspective on the design of advanced PE systems.

An enzyme cascade sensor with resistance to the inherent intermediate product by logic-controlled peroxidase mimic catalysis.

Enzyme cascade sensors usually could not discriminate between the target and intermediate product. Herein, based on "AND" logic-controlled activation of the glucose oxidase-copper peroxide sensing system, enzyme cascade detection for glucose with resistance to inherently existing intermediate product H2O2 was reported for the first time, which may provide a novel way for facilitating enzyme cascade sensing.

Applications of DNA-nanozyme-based sensors.

Since the discovery of the enzyme-like activities of nanomaterials, the study of nanozymes has become one of the most popular research frontiers of diverse areas including biosensors. DNA also plays a very important role in the construction of biosensors. Thus, the idea of combined applications of nanozymes with DNA (DNA-nanozyme) is very attractive for the development of nanozyme-based biosensors, which has attracted considerable interest of researchers. To date, many sensors based on DNA-functionalized or templated nanozymes have been reported for the detection of various targets and highly accelerated the development of nanozyme-based sensors. In this review, we summarize the main applications and advances of DNA-nanozyme-based sensors. Additionally, perspectives and challenges are also discussed at the end of the review.

Construction of Molecular Sensing and Logic Systems Based on Site-Occupying Effect-Modulated MOF-DNA Interaction.

Interactions between metal-organic frameworks (MOFs) and nucleic acids are of great importance in molecular assembly. However, current MOF-nucleic acid interactions lack diversity and are normally realized in an uncontrollable manner. Herein, the interaction of zirconium-based MOFs (Zr-MOFs) with nucleic acids is enabled by the formation of Zr-O-P bonds and further manipulated by a phosphate-induced site-occupying effect. Covering Zr ions in clusters of MOFs with phosphates impedes the formation of Zr-O-P bonds with nucleic acids, rendering the MOF-nucleic acid interaction tunable and stimulus-responsive. Notably, the experimental results demonstrate that various phosphates, Zr-MOFs, and nucleic acids can all be adopted in the tunable interaction. On the basis of these findings, fluorescent DNA and typical Zr-MOFs are proposed as functional probe-quencher pairs to establish molecular sensing and logic systems. Accordingly, alkaline phosphatase and inorganic pyrophosphatase can be quantified simultaneously, and the overall relation of different phosphates and phosphatases is facilely displayed. The work provides a general strategy for modulating MOF-nucleic acid interactions, which is conducive to the development of molecular intelligent systems.

Sensitive determination of formamidopyrimidine DNA glucosylase based on phosphate group-modulated multi-enzyme catalysis and fluorescent copper nanoclusters.

In this work, a method for quantifying the activity of formamidopyrimidine DNA glucosylase (Fpg) was designed based on phosphate group (P)-modulated multi-enzyme catalysis and fluorescent copper nanoclusters (CuNCs). By eliminating 8-oxoguanine from double-stranded DNA, Fpg generates a nick with P at both 3' and 5' termini. Subsequently, part of the DNA is digested by 5'P-activated lambda exonuclease (λ Exo), and the generated 3'P disables exonuclease I (Exo I), resulting in the generation of single-stranded DNA containing poly(thymine) (poly(T)). Using poly(T) as templates, CuNCs were prepared to emit intense fluorescence as the readout of this method. However, in the absence of Fpg, the originally modified 5'P triggers the digestion of λ Exo. In this case, fluorescence emission is not obtained because CuNCs cannot be formed without DNA templates. Therefore, the catalysis of λ Exo and Exo I can be tuned by 5'P and 3'P, which can be further used to determine the activity of Fpg. The fluorescent Fpg biosensor works in a "signal-on" manner with the feature of "zero" background noise, and thus shows desirable analytical features and good performance. Besides, Fpg in serum samples and cell lysate could be accurately detected with the biosensor, indicating the great value of the proposed system in practical and clinical analysis.

Formation of a Photoelectrochemical Z-Scheme Structure with Inorganic/Organic Hybrid Materials for Evaluation of Receptor Protein Expression on the Membrane of Cancer Cells.

Quantitative analysis of receptor protein expression is essential to give new insights into tumor-related research. Benefitting from their high sensitivity and low background, photoelectrochemical (PEC) platforms are considered as powerful tools for evaluating the expression of receptor proteins. Herein, to reduce the cytotoxicity and facilitate the subsequent assembly, l-cysteine-modified Ag-ZnIn2S4 quantum dots (l-Cys AZIS QDs) are prepared and PEC responses under the irradiation of long wavelength light are obtained. To further improve the PEC behavior, iron phthalocyanine (FePc) is employed to form a Z-scheme structure with l-Cys AZIS QDs. The Z-scheme structure based on l-Cys AZIS QDs/FePc hybrid materials exhibits high photo-to-electric conversion efficiency and can be excited with near-infrared range light. Because hyaluronic acid linked to photoactive materials can recognize CD44 expressed on the membrane of cancer cells, cancer cells are immobilized onto l-Cys AZIS QDs/FePc hybrid materials, inducing a decrease of the photocurrent intensity. Consequently, a PEC cytosensor is constructed to quantify cancer cells expressing CD44. The PEC analytical platform is able to determine A549 cells in the range of 2 × 102 to 4.5 × 106 cells/mL, and a detection limit of 15 cells/mL is realized in the case of S/N = 3. In addition, the expression of CD44 in A549 and other five cancer cells is measured with this PEC method. Depending on our data, the expression of CD44 in different cancer cells is distinct, indicating great potential of this method in receptor protein-related studies.