Targets For Approaches Research Articles

Nanocarrier-mediated modulation of cGAS-STING signaling pathway to disrupt tumor microenvironment.

The cGAS-STING signaling plays an important role in the immune response in a tumor microenvironment (TME) of triple-negative breast cancer (TNBC). The acute and controlled activation of cGAS-STING signaling results in tumor suppression, while chronic activation of cGAS-STING signaling results in immune-suppressive TME that could result in tumor survival. There is a need, therefore, to develop therapeutic strategies for harnessing tumor suppressive effects of cGAS-STING signaling while minimizing the risks associated with chronic activation. Combination therapies and nanocarriers-based delivery of cGAS-STING agonists have emerged as promising strategies in immunotherapy for controlled modulation of cGAS-STING signaling in cancer. These approaches aim to optimize the tumor suppressive effects of the cGAS-STING pathway while minimizing the challenges associated with modulators of cGAS-STING signaling. In the present review, we discuss recent advancements and strategies in combination therapies and nanocarrier-based delivery systems for effectively controlling cGAS-STING signaling in cancer immunotherapy. Further, we emphasized the significance of nanocarrier-based approaches for effective targeting of the cGAS-STING signaling, tackling resistance mechanisms, and overcoming key challenges like immune suppression, tumor heterogeneity, and off-target effects.

Envisioning Glucose Transporters (GLUTs and SGLTs) as Novel Intervention against Cancer: Drug Discovery Perspective and Targeting Approach.

Metabolic reprogramming and altered cellular energetics have been recently established as an important cancer hallmark. The modulation of glucose metabolism is one of the important characteristic features of metabolic reprogramming in cancer. It contributes to oncogenic progression by supporting the increased biosynthetic and bio-energetic demands of tumor cells. This oncogenic transformation consequently results in elevated expression of glucose transporters in these cells. Moreover, various cancers exhibit abnormal transporter expression patterns compared to normal tissues. Recent investigations have underlined the significance of glucose transporters in regulating cancer cell survival, proliferation, and metastasis. Abnormal regulation of these transporters, which exhibit varying affinities for hexoses, could enable cancer cells to efficiently manage their energy supply, offering a crucial edge for proliferation. Exploiting the upregulated expression of glucose transporters, GLUTs, and Sodium Linked Glucose Transporters (SGLTs), could serve as a novel therapeutic intervention for anti-cancer drug discovery as well as provide a unique targeting approach for drug delivery to specific tumor tissues. This review aims to discussthe previous and emerging research on the expression of various types of glucose transporters in tumor tissues, the role of glucose transport inhibitors as a cancer therapy intervention as well as emerging GLUT/SGLT-mediated drug delivery strategies that can be therapeutically employed to target various cancers.

Approaches for GC-HRMS Screening of Organic Microcontaminants: GC-APCI-IMS-QTOF versus GC-EI-QOrbitrap.

This study explores the capabilities of GC-APCI-IMS-QTOF MS and GC-EI-QOrbitrap MS in screening applications and different strategies for wide-scope screening of organic microcontaminants using target suspect and nontarget approaches. On one side, GC-APCI-IMS-QTOF MS excels at preserving molecular information and adds ion mobility separation, facilitating screening through the list of componentized features containing accurate mass, retention time, CCS, and fragmentation data. On the other side, the extensive and robust fragmentation of GC-EI-QOrbitrap MS allows the application of different strategies for target and nontarget approaches using the NIST library spectra. Our findings revealed that GC-EI-QOrbitrap MS is more sensitive in target approaches. Automated workflows for suspect screening in GC-APCI-IMS-QTOF MS minimize false annotations but face challenges with false negatives due to in-source fragmentation and limitations when using in silico fragmentation tools. Conversely, a nontarget approach in GC-EI-QOrbitrap MS can reliably identify unknowns but results in more false annotations in complex matrices. This work highlights the strengths and limitations of each system and guides for their optimal application for wide-scope screening in environmental and food safety applications.

Incorporating Transformation Products for an Integrated Assessment of Antibiotic Pollution and Risks in Surface Water.

The widespread presence of antibiotics in aquatic ecosystems is a global challenge, yet the occurrence and risks associated with their transformation products (TPs) remain poorly understood. This study investigated the occurrence and potential risks of antibiotics and their TPs in water along the Chaobai River in Beijing. We used high-resolution mass spectrometry and an integrated target, suspect, and nontarget screening approach to identify 21 parent antibiotics and 78 TPs among 90 water samples, with the majority from macrolides and sulfonamides. Notably, target quantification and machine-learning-assisted semiquantification revealed that the cumulative concentrations of TPs were higher than the cumulative concentrations of parent compounds, with average contributions of TPs ranging between 50.7 and 63.7%. Most downstream water samples were largely influenced by domestic sewage, as indicated by the significantly higher concentrations and proportions of TPs, as well as the greater diversity in their composition profiles compared to upstream and reservoir samples. Moreover, of the 78 TPs, 26.9, 67.9, and 6.4% exhibited greater persistence, mobility, or toxicity than their parent antibiotics, respectively. Sixteen macrolide TPs presented both greater ecological risks to aquatic organisms and higher resistance selection risks than their parent antibiotics. TPs contributed substantially to the overall antibiotic-related risks by an average of between 31.2 and 54.1%. This study highlights the occurrence of antibiotic TPs in river water, underscoring the need to consider TPs in comprehensive risk assessments of antibiotics.

Small Molecule Modulators of AMP-Activated Protein Kinase (AMPK) Activity and Their Potential in Cancer Therapy.

AMP-activated protein kinase (AMPK) is a central mediator of cellular metabolism and is activated in direct response to low ATP levels. Activated AMPK inhibits anabolic pathways and promotes catabolic activities that generate ATP through the phosphorylation of multiple target substrates. AMPK is a therapeutic target for activation in several chronic metabolic diseases, and there is increasing interest in targeting AMPK activity in cancer where it can act as a tumor suppressor or conversely it can support cancer cell survival. Small molecule AMPK activators and inhibitors have demonstrated some success in suppressing cancer growth, survival, and drug resistance in preclinical cancer models. In this perspective, we summarize the role of AMPK in cancer and drug resistance, the influence of the tumor microenvironment on AMPK activity, and AMPK activator and inhibitor development. In addition, we discuss the potential importance of isoform-selective targeting of AMPK and approaches for selective AMPK targeting in cancer.

Development, Characterization, and Evaluation of Chi-Tn mAb-Functionalized DOTAP-PLGA Hybrid Nanoparticles Loaded with Docetaxel for Lung Cancer Therapy

Background/Objectives: The focus of this study was to prepare and characterize docetaxel (DCX)-loaded lipid/polymer hybrid nanoparticles (LPHNps) functionalized with the monoclonal antibody (mAb) Chi-Tn for a potential active targeting approach in lung cancer treatment. Methods: We synthesized DOTAP-PLGA hybrid nanoparticles loaded with DCX and functionalized them with Chi-Tn mAb through a biotin–avidin approach. The physicochemical characterization involved dynamic light scattering, transmission electron microscopy, Raman spectroscopy, and atomic force microscopy. The in vitro and in vivo evaluations encompassed uptake studies, cell viability tests, and the assessment of tumor growth control in a lung cancer model. Results: The nanoparticles featured a hydrophobic PLGA core with 99.9% DCX encapsulation efficiency, surrounded by a DOTAP lipid shell ensuring colloidal stability with a high positive surface charge. The incorporation of PEGylated lipids on their surface helps evade the immune system and facilitate Chi-Tn mAb attachment. The resulting nanoparticles exhibit a spherical shape with monodisperse particle sizes averaging 250 nm, and demonstrate sustained drug release. In vitro uptake studies and viability assays conducted in A549 cancer cells show that the Chi-Tn mAb enhances nanoparticle internalization and significantly reduces cell viability. In vivo studies demonstrate a notable reduction in tumor volume and an increased survival rate in the A549 tumor xenograft mice model when DCX was encapsulated in nanoparticles and targeted with Chi-Tn mAb in comparison to the free drug. Conclusions: Therefore, Chi-Tn-functionalized LPHNps hold promise as carriers for actively targeting DCX to Tn-expressing carcinomas.

Autonomous Docking Manoeuvre Testing in the Framework of the ERMES Experiment

Abstract The rise of the “New Space Economy” has expanded access to low-Earth orbits for commercial, non-profit, and educational entities. This has driven significant growth in the small satellite market, offering a low-cost solution for various missions. Autonomous proximity operation systems for small satellites are actively studied for their wide-ranging applications. Experimental Rendezvous in Microgravity Environment Study (ERMES) is a student project, which aimed at testing an autonomous docking manoeuvre between two free-flying CubeSats mock-ups in a reduced gravity environment. The manoeuvre is characterized by an active Chaser and cooperative Target approach. In particular, the Chaser is equipped with a cold gas propulsive system based on expendable $$\hbox {CO}_{2}$$ CO 2 cartridges for three-dimensional manoeuvering, whereas the Target has a set of reaction wheels for attitude control. The magnetic post-manoeuvre connection is achieved thanks to a dedicated miniaturized docking interface. Moreover, the reduced gravity conditions have been achieved by participating in the European Space Agency (ESA) $$79^{th}$$ 79 th Parabolic Flight Campaign thanks to the selection in the ESA Fly Your Thesis! Programme 2022 (FYT). This article provides an overview of the ERMES experiment, discussing its main objectives and key design solutions. It first describes the design of the Guidance Navigation and Control subsystems of the two mock-ups, then discusses the results of the parabolic flight campaign, and finally focuses on the analysis of a specific parabolic test, where the Chaser was able to dock by recovering a high overall misalignment.

Navigating liver cancer: Precision targeting for enhanced treatment outcomes.

Cancer treatments such as surgery and chemotherapy have several limitations, including ineffectiveness against large or persistent tumors, high relapse rates, drug toxicity, and non-specificity of therapy. Researchers are exploring advanced strategies for treating this life-threatening disease to address these challenges. One promising approach is targeted drug delivery using prodrugs or surface modification with receptor-specific moieties for active or passive targeting. While various drug delivery systems have shown potential for reaching hepatic cells, nano-carriers offer significant size, distribution, and targetability advantages. Engineered nanocarriers can be customized to achieve effective and safe targeting of tumors by manipulating physical characteristics such as particle size or attaching receptor-specific ligands. This method is particularly advantageous in treating liver cancer by targeting specific hepatocyte receptors and enzymatic pathways for both passive and active therapeutic strategies. It highlights the epidemiology of liver cancer and provides an in-depth analysis of the various targeting approaches, including prodrugs, liposomes, magneto-liposomes, micelles, glycol-dendrimers, magnetic nanoparticles, chylomicron-based emulsion, and quantum dots surface modification with receptor-specific moieties. The insights from this review can be immensely significant for preclinical and clinical researchers working towards developing effective treatments for liver cancer. By utilizing these novel strategies, we can overcome the limitations of conventional therapies and offer better outcomes for liver cancer patients.

Phospholipase C epsilon 1 as a therapeutic target in cardiovascular diseases.

Phospholipase C epsilon 1 (PLCε1) can hydrolyze phosphatidylinositol-4,5-bisphosphate and phosphatidylinositol-4-phosphate at the plasma membrane and perinuclear membrane in the cardiovascular system, producing lipid-derived second messengers. These messengers are considered prominent triggers for various signal transduction processes. Notably, diverse cardiac phenotypes have been observed in cardiac-specific and global Plce1 knockout mice under conditions of pathological stress. It is well established that the cardiac-specific Plce1 knockout confers cardioprotective benefits. Therefore, the development of tissue/cell-specific targeting approaches is critical for advancing therapeutic interventions. This review aims to distill the foundational biology and functional significance of PLCε1 in cardiovascular diseases, as well as to explore potential avenues for research and the development of novel therapeutic strategies targeting PLCε1. Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, with incidence rates escalating annually. A comprehensive understanding of the multifaceted role of PLCε1 is essential for enhancing the diagnosis, management, and prognostic assessment of patients suffering from cardiovascular diseases.

AlphaFold and Docking Approaches for Antibody-Antigen and Other Targets: Insights From CAPRI Rounds 47-55.

Accurate modeling of the structures of protein-protein complexes and other biomolecular interactions represents a longstanding and important challenge for computational biology. The Critical Assessment of PRedicted Interactions (CAPRI) experiment has served for over two decades as a key means to assess and compare current approaches and methods through blind predictive scenarios, highlighting useful strategies, and new developments. Here we describe the performance of our laboratory's team in recent CAPRI rounds, which included submissions for 10 modeling targets. Our team utilized a range of docking and modeling approaches, including ZDOCK, Rosetta, and ZRANK, to model, refine, and score protein-protein and protein-DNA complexes. For recent targets we utilized adaptations of AlphaFold to generate models, leading to near-native models for an antibody-peptide target, and a highly accurate (but low ranked) model for an antibody-MHC complex. These results underscore the utility of AlphaFold-based protocols for predictive protein complex modeling, including for immune recognition, and highlight considerations regarding the use of AlphaFold confidence metrics in model selection.

Engineering a membrane protein chaperone to ameliorate the proteotoxicity of mutant huntingtin

Toxic protein aggregates are associated with various neurodegenerative diseases, including Huntington’s disease (HD). Since no current treatment delays the progression of HD, we develop a mechanistic approach to prevent mutant huntingtin (mHttex1) aggregation. Here, we engineer the ATP-independent cytosolic chaperone PEX19, which targets peroxisomal membrane proteins to peroxisomes, to remove mHttex1 aggregates. Using yeast toxicity-based screening with a random mutant library, we identify two yeast PEX19 variants and engineer equivalent mutations into human PEX19 (hsPEX19). These variants effectively delay mHttex1 aggregation in vitro and in cellular HD models. The mutated hydrophobic residue in the α4 helix of hsPEX19 variants binds to the N17 domain of mHttex1, thereby inhibiting the initial aggregation process. Overexpression of the hsPEX19-FV variant rescues HD-associated phenotypes in primary striatal neurons and in Drosophila. Overall, our data reveal that engineering ATP-independent membrane protein chaperones is a promising therapeutic approach for rational targeting of mHttex1 aggregation in HD.

Efficacy of metformin and verteporfin treatment alone or in combination in a murine head and neck cancer xenograft model.

Despite treatment advances, head and neck squamous cell carcinoma (HNSCC) still poses a significant global health challenge. Combination therapies have emerged as more effective strategies than traditional chemotherapy in clinical practice by improving tumor response rates and patient survival while minimizing treatment-related toxicity. This study investigates the anticancer effects of metformin and verteporfin (Yes-associated protein 1 [YAP1] inhibitor) alone or in combination in HNSCC using vitro and in vivo approaches. Quantitative RT-PCR analysis of HNSCC cell lines reveals upregulation of YAP1 and related genes in the Hippo signaling pathway. Cell viability assays demonstrate a beneficial synergistic effect between metformin and verteporfin in inhibiting HNSCC tumor growth. In male BALB/cAJcl-nu/nu mice harboring HNSCC tumor xenografts, intraperitoneal administration of metformin and verteporfin enhances the inhibitory effect on tumor growth and suppresses YAP1 nuclear translocation when compared to vehicle or monotherapies. Furthermore, combination of these drugs reduces tumor cell proliferation (marked by Ki-67) and inhibits phosphoS6 ribosomal protein, as observed through immunofluorescent and immunohistochemical (IHC) analyses. The in vivo study underscores the therapeutic potential of the dual targeting approach with metformin and verteporfin in treating HNSCC, with minimal toxicity.

Promising new drugs and therapeutic approaches for treatment of ovarian cancer—targeting the hallmarks of cancer

Abstract Ovarian cancer remains the most lethal gynecological malignancy. Despite the approval of promising targeted therapy such as bevacizumab and PARP inhibitors, 5-year survival has not improved significantly. Thus, there is an urgent need for new therapeutics. New advancements in therapeutic strategies target the pivotal hallmarks of cancer. This review is giving an updated overview of innovative and upcoming therapies for the treatment of ovarian cancer that focuses specific on the hallmarks of cancer. The hallmarks of cancer constitute a broad concept to reenact complexity of malignancies and furthermore identify possible targets for new treatment strategies. For this purpose, we analyzed approvals and current clinical phase III studies (registered at ClinicalTrials.gov (National Library of Medicine, National Institutes of Health; U.S. Department of Health and Human Services, 2024)) for new drugs on the basis of their mechanisms of action and identified new target approaches. A broad spectrum of new promising drugs is currently under investigation in clinical phase III studies targeting mainly the hallmarks “self-sufficiency in growth signals,” “genomic instability,” and “angiogenesis.” The benefit of immune checkpoint inhibitors in ovarian cancer has been demonstrated for the first time. Besides, targeting the tumor microenvironment is of growing interest. Replicative immortality, energy metabolism, tumor promoting inflammation, and the microbiome of ovarian cancer are still barely targeted by drugs. Nevertheless, precision medicine, which focuses on specific disease characteristics, is becoming increasingly important in cancer treatment. Graphical Abstract

Examining Arginase-1 Trimerization Uncovers a Promising Allosteric Site for Inhibition.

Arginase-1 (ARG-1) is a promising target for cancer immunotherapy, but the small size and the highly polar nature of its catalytic site present significant challenges for inhibitor development. An alternative strategy to induce enzyme inhibition by targeting protein oligomerization has been developed recently, offering several advantages such as increased selectivity, promotion of protein degradation, and potential substoichiometric inhibition. In this study, we demonstrated that only trimeric ARG-1 is active, which was confirmed by producing monomeric arginase-1. Through in silico-driven site-directed mutagenesis, we identified an allosteric site involving five key amino acids responsible for ARG-1 trimerization. We further demonstrated the covalent modification of a key arginine residue within this pocket using phenylglyoxal disrupted ARG-1 oligomerization. Although phenylglyoxal has limited potency, it effectively supports the concept of ARG-1 inhibition via homomeric disruption, validating this allosteric targeting approach.

Ethnic disparities in HbA1c and hypoglycemia among youth with type 1 diabetes: beyond access to technology, social deprivation and mean blood glucose

IntroductionThe UK national pediatric diabetes audit reports higher HbA1c for children and young people (CYP) with type 1 diabetes (T1D) of Black ethnicity compared with White counterparts. This is presumably...

Functional epitope mapping of cell surface glucose-regulated protein 94: A combinatorial approach for therapeutic targeting.

Glucose-regulated protein 94 (GRP94) overexpression plays a critical role in tumor cell survival across various cancers. Previously, we developed K101.1, a fully human antibody targeting cell surface GRP94, which effectively inhibits tumor angiogenesis in colorectal cancer (CRC). This study aims to identify K101.1's interaction site and further elucidate GRP94's role in tumor angiogenesis. In an HT29 CRC xenograft mouse model, K101.1 reduced tumor growth and angiogenesis by 30% and 69%, respectively, without inducing severe toxicity. Using hydrogen‑deuterium exchange mass spectrometry, we identified the binding site of K101.1 on GRP94, analyzing 225 peptides with 94.5% sequence coverage and a redundancy score of 4.20. This revealed a linear epitope (Glu26-Ala34) as the specific binding site. The binding was further validated via enzyme-linked immunosorbent assay, and human umbilical vein endothelial cell tube formation assays using a synthetic epitope peptide corresponding to the identified epitope. Our findings suggest that this epitope is functionally involved in GRP94-mediated angiogenesis and is integral to its proangiogenic activity. By integrating epitope profiling with complementary experimental approaches, this study advances the understanding of GRP94's role in CRC angiogenesis and provides new insights for developing targeted cancer therapies and vaccines, offering promising avenues for CRC prevention and treatment.

Translation Research in Therapeutic Approaches from Conventional to Novel Nano-therapeutics for Rheumatoid Arthritis Treatment

Rheumatoid arthritis is a systemic autoimmune disorder related to joint inflammation, bone erosion, and deformity. Numerous studies indicate that the causes and consequences of RA are still being debated, and therapeutic strategies are in the translation stage. Non-steroidal anti-inflammatory drugs continue to be often used to relieve pain. Still, due to their poor efficacy, failure to halt the spread of the disease, and undesirable adverse effects, they are no longer regarded as first-line treatments. The development of biologic DMRDs designed to reduce the inflammatory response led to substantial changes to the strategy for managing this disease. Although biologic DMRDs have made significant strides in the management of Rheumatoid arthritis, certain patients' lack of response to biological approaches and therapy cessation due to systemic toxicity are unresolved problems. Therefore, to improve the in vivo effect and reduce systemic adverse effects, new approaches are needed to proactively target and transport therapeutic molecules to target sites. The intriguing method of nanotechnology enables the encapsulation of drugs to prevent their deterioration and systemic adverse effects. The next generation of Rheumatoid arthritis therapies might be based on advances in nanomaterial-based drug delivery, Trojan horse, and antibody targeting approaches. This article presents an overview of the advancements in Rheumatoid arthritis therapy, ranging from traditional methods to recent cutting-edge, ongoing pre-clinical and clinical approaches.

Screening optimal DC-targeting peptide to enhance the immune efficacy of recombinant Lactobacillus expressing RHDV VP60

ABSTRACT Dendritic cells (DCs) present an ideal target for delivering immunogenic cargo due to their potent antigen-presenting capabilities. This targeting approach holds promise in vaccine development by enhancing the efficiency of antigen recognition and capture by DCs. To identify a high-affinity targeting peptide binding to rabbit DCs, rabbit monocyte-derived DCs (raMoDCs) were isolated and cultured, and a novel peptide, HS (HSLRHDYGYPGH), was identified using a phage-displayed peptide library. Alongside HS, two other DC-targeting peptides, KC1 and MY, previously validated in our laboratory, were employed to construct recombinant Lactgobacillus reuteri fusion-expressed rabbit hemorrhagic disease virus (RHDV) capsid protein VP60. These recombinant Lactobacillus strains were named HS-VP60/L. reuteri, KC1-VP60/L. reuteri, and MY-VP60/L. reuteri. The ability of these recombinant Lactobacillus to bind rabbit DCs was evaluated both in vivo and in vitro. Results demonstrated that the DC-targeting peptide KC1 significantly enhanced the capture efficiency of recombinant Lactobacillus by raMoDCs, promoted DC maturation, and increased cytokine secretion. Furthermore, oral administration of KC1-VP60/L. reuteri effectively induced SIgA and IgG production in rabbits, prolonged rabbit survival post-challenge, and reduced RHDV copies in organs. In summary, the DC-targeting peptide KC1 exhibited robust binding to raMoDCs, and recombinant Lactobacillus expressing KC1-VP60 protein antigens efficiently induced systemic and mucosal immune responses in rabbits, conferring protective efficacy against RHDV. This study offers valuable insights for the development of novel RHDV vaccines.

Targeting Transcriptional Regulators Affecting Acarbose Biosynthesis in Actinoplanes sp. SE50/110 Using CRISPRi Silencing.

Acarbose, a pseudo-tetrasaccharide produced by Actinoplanes sp. SE50/110, is an α-glucosidase inhibitor and is used as a medication to treat type 2 diabetes. While the biosynthesis of acarbose has been elucidated, little is known about its regulation. Gene silencing using CRISPRi allows for the identification of potential regulators influencing acarbose formation. For this purpose, two types of CRISPRi vectors were established for application in Actinoplanes sp. SE50/110. The pCRISPomyces2i vector allows for reversible silencing, while the integrative pSETT4i vector provides a rapid screening approach for many targets due to its shorter conjugation time into Actinoplanes sp. These vectors were validated by silencing the known acarbose biosynthesis genes acbB and acbV, as well as their regulator, CadC. The reduction in product formation and the diminished relative transcript abundance of the respective genes served as evidence of successful silencing. The vectors were used to create a CRISPRi-based strain library, silencing 50 transcriptional regulators, to investigate their potential influence in acarbose biosynthesis. These transcriptional regulatory genes were selected from previous experiments involving protein-DNA interaction studies or due to their expression profiles. Eleven genes affecting the yield of acarbose were identified. The CRISPRi-mediated knockdown of seven of these genes significantly reduced acarbose biosynthesis, whereas the knockdown of four genes enhanced acarbose production.

Folate receptor-targeted thiol-maleimide clicked chitosan/carboxymethyl cellulose nanoparticles for cisplatin delivery in oral carcinoma.

This study aimed to develop cisplatin (CDDP)-loaded folic acid (FA)-decorated nanoparticles (NPs) as targeted drug carrier towards overexpressed folate receptors on the oral carcinoma cell line (KB cells). The FA-conjugated thiolated succinyl chitosan (FA-SH-SCS) and maleimide-grafted-carboxymethyl cellulose (CMC-MAL) were synthesized and acquired in the preparation of NPs via thiol-maleimide click reaction. The physicochemical characteristics, drug loading, and drug release of the FA-decorated NPs (FA-NPs) were examined. Also, the in vitro biocompatibility, cellular uptake, and cell death mechanism were investigated. Relatively spherical NPs with negative charge were obtained with a size of approximately 200 nm. The formation of FA-NPs through click reaction was confirmed by the pH change and Ellman's assay. The release of CDDP from the FA-NPs was influenced by the acidic tumor environment condition. The FA-NPs were non-toxic to the normal cells. Furthermore, FA-NPs improved the cellular uptake of CDDP in oral carcinoma cells through specific recognition of folate receptors by FA-NPs. The delivery of CDDP by FA-NPs to the KB cell induced the apoptotic cell death pathway. Therefore, FA-NPs presented the potential to be effective nanocarriers for CDDP delivery in the treatment of oral cancer via active targeting approach.