Cancer remains a leading global health challenge, driving the search for effective and targeted therapies. This review explores the potential of pectin-based nanoparticles in cancer treatment, emphasizing their role as a promising biomaterial in nanoparticle formulation. The review begins by discussing the structure, properties, and extraction methods of pectin, highlighting its biocompatibility and biodegradability, which are crucial for novel drug delivery systems. The review further delves into the manufacturing techniques of pectin-based NPs and examines various targeting strategies, including passive mechanisms like the surged permeability and retention effect, and active approaches such as ligand-mediated targeting. Strategies for overcoming biological barriers are also discussed. The review also entails the application of pectin NPs to treat different type of cancers, including breast, lung, brain, liver, and pancreatic cancers, underscoring their potential to enhance the therapeutic outcomes and minimise adverse effects. This review provides insights into the advancements and future directions of pectin-based NPs in oncology.

Preserving plant biodiversity and making sustainable use of genetic resources in agriculture is a topical issue with ecological, economic, and social repercussions. In Italy, some onion (Allium cepa L.) varieties, only cultivated by local farmers, are neglected and worth to be valorised. In this work, a comparative chemical and biological study of nine onion varieties and four commercially available ones was carried out by combining the acquisition of large, high-resolution experimental datasets (LC-HR -ESI-MS2) with molecular networking strategy and chemometric tools. All extracts were investigated for antioxidant properties and antiangiogenic activity by two in vivo models, chick chorioallantoic membrane (CAM), and zebrafish embryos. 'Ciatta', 'Massese', and 'Fiorentina' indigenous varieties showed potent inhibitory effects on blood vessel formation, comparably with the commercial reference variety 'Tropea'. The bioactive profile rich in phenols, alkaloids, saponins, and fatty acids of these varieties revealed their health-promoting potential and importance for the agri-food chain.

As possible delivery systems for anticancer medications and molecular imaging, polymer nanoparticles have tremendous potentials. This study aimed to develop a novel drug delivery system using PTX conjugated β-cyclodextrin inclusion complex-capped gold nanoparticles (PTX-β-CD-AuNPs) to manage triple-negative breast cancer (TNBC). Characterization techniques confirmed the successful synthesis of PTX-β-CD-AuNPs with mean size of around 43 nm. In vitro studies demonstrated enhanced cytotoxicity of PTX-β-CD-AuNPs compared to the individual components, as evidenced by MTT assay results. Furthermore, morphological analysis revealed significant alterations in cancer cell morphology, including cytoskeletal disruption and apoptosis induction. The clonogenic assay demonstrated the ability of PTX-β-CD-AuNPs to suppress colony formation, indicating potential targeting of cancer stem cells. Additionally, migration assays showed reduced cell migratory capacity, suggesting potential anti-metastatic effects. These findings illustrate the efficacy of PTX-β-CD-AuNPs as a promising nanocarrier for treating TNBC. To assess the therapeutic efficacy of PTX-β-CD-AuNPs and clarify the mechanisms behind it, additional study is essential.

Depicting a global landscape of essential gene-targeting drugs would provide more opportunities for cancer therapy. However, a systematic investigation on drugs targeting essential genes still has not been reported. We suppose that drugs targeting cancer-type-specific essential genes would generally have less toxicity than those targeting pan-cancer essential genes. A scoring function-based strategy was developed to identify cancer-type-specific targets and drugs. The EssentialitySpecificityScore ranked the essential genes in 19 cancer types, and 1151 top genes were identified as cancer-type-specific targets. Combining target-drug interaction databases with research/marketing status, 370 cancer-type-specific drugs were identified, bound to 100 out of all identified targets. Profiles of applied cancer types of identified targets and drugs illustrate the scoring strategy's effectiveness: most drugs apply to cancer types <10. Seven drugs with no previous anticancer evidence were validated in 11 lung adenocarcinoma cell lines, and lower inhibition rates (from 9.4% to 44.0%) were observed in 10 normal cell lines. This difference is statistically significant (Student's t-test, P ≤ .0001), confirming the rationality of our supposition. Our built EGKG (Essential Gene Knowledge Graph) forms a computational basis to uncover essential gene targets and drugs for specific cancer types. It is available at http://gepa.org.cn/egkg/. Also, our experimental result suggests that combining drugs with orthogonal essentiality may be an alternative way to improve anticancer effects while maintaining biocompatibility. The code and data are available at https://github.com/KKINGA1/EGKG_data_process.

Consolidative PD-L1 inhibitors after concurrent chemoradiotherapy (cCRT) have become standard care in locally advanced non-small cell lung cancer (LA-NSCLC). However, the correlation between immune-related adverse event (irAE) characteristics and patient outcomes remains unclear.

Menaquinone (MK), which is also known as vitamin K2, is a kind of lipoquinone that, unlike humans, is biosynthesized in bacteria through a series of steps as a necessary component of their respiratory chain for electron transport among various components of the bacterial cell membrane. MKs are receiving increasing attention as they play several essential biological roles in humans.

Colorectal cancer (CRC) ranks as the third most common cancer globally, with 1.9 million newly diagnosed cases annually and nearly 935,000 deaths, posing substantial healthcare challenges worldwide. Food-derived bioactive peptides (FDBPs) are natural, non-toxic, and cost-effective compounds that exhibit significant potential in combating CRC. However, a comprehensive review summarizing FDBPs sources, peptide sequences, their anti-CRC effects, and underlying mechanisms is still lacking. Consequently, the present study discussed the CRC inhibitory effects and action mechanisms of FDBPs from different protein sources. We found that plant proteins, animal proteins, milk proteins, and microbial proteins are all ideal sources for producing peptides with high anti-CRC activity. Several peptides isolated from these proteins can promote apoptosis, inhibit metastasis, reduce invasion of CRC, and finally suppress tumor growth. Notably, low-molecular-weight FDBPs, particularly those below 1 kDa and rich in Asp, Gln, Lys, Gly, and Ser, exhibit better stability and stronger anti-CRC efficacy. The anti-CRC activity of FDBPs is associated with balancing the gut microbiota, activating the p38 MAPK pathway, and inhibiting the PI3K/AKT signaling pathway; however, the upstream and downstream regulatory mechanisms remain unclear. Additionally, we discovered that nanoparticle and glycopeptide modifications can enhance the activity and stability of anti-CRC peptides, enabling more precise delivery to cancer sites. Our review will be of interest for the design of natural anti-CRC drugs.

Resistance limits the efficacy and durability of immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC). Therefore, we conducted a retrospective cohort study to investigate the outcomes and characteristics of HCC patients with resistance to immunotherapy. Patients with HCC who have received ICIs at Eastern Hepatobiliary Surgery Hospital between 2016 and 2021 were retrospectively screened and divided into primary resistance, secondary resistance, and durable response group. Time to progression (TTP), overall survival (OS), subsequent management and post-progression survival (PPS) were analyzed. Of 496 patients included, 229 (46.2%) and 141 (28.4%) patients developed primary and secondary resistance, and 126 (25.4%) patients achieved a durable response, the median TTP was 2.83 [2.56-3.09] months, 11.93 [10.45-13.40] months, and not reached, respectively, whereas the median OS was 12.83 [10.36-15.30] months, 31.53 [28.09-34.97] and not reached, respectively. Multivariate logistic regression revealed that Child-Pugh score, BCLC stage, and combined systemic therapies (ICI plus bevacizumab or lenvatinib versus ICI monotherapy) were independently associated with primary resistance, and only combined systemic therapies (ICI plus bevacizumab versus ICI monotherapy) were independently associated with secondary resistance. AFP levels were independently associated with PPS in patients with primary resistance, while post-progression therapies (ICI-based therapies versus others) were independently associated with PPS in patients with resistance. The risk of resistance was notably lower in patients receiving the combination of ICI plus bevacizumab. High AFP levels were associated with the survival of patients with primary resistance. ICI-based maintenance therapy after resistance may provide a significant survival advantage for HCC patients.

BACKGROUND Hepatocellular carcinoma (HCC) with vascular invasion at advanced stage is not indicated for surgical options. Conversion therapy is used for unresectable HCC to downstage. Chemotherapy can be more precisely targeted to HCC by using hepatic artery infusion. Bevacizumab and sintilimab are available systemic therapies for HCC. This report describes a 50-year-old man with advanced HCC associated with multiple venous tumor thromboses treated with hepatic artery infusion chemotherapy (HAIC) combined with bevacizumab and sintilimab conversion therapy. CASE REPORT A 50-year-old man was admitted to the hospital due to elevated alpha-fetoprotein (AFP) level in July 2022. Abdominal computed tomography angiography (CTA) revealed a large HCC with multiple venous tumor thromboses. Pulmonary CTA detected arterial embolism and multiple solid nodules. He received HAIC combined with bevacizumab and sintilimab every 3 weeks, and achieved partial response after 3 cycles. However, in March 2023, levels of AFP and protein induced by vitamin K absence-II (PIVKA-II) were re-elevated, showing some pulmonary nodules were enlarged, which was confirmed as pulmonary metastases by positron emission tomography/computed tomography (PET/CT). Subsequently, transarterial chemoembolization (TACE) with bevacizumab and sintilimab was performed, and stereotactic body radiation therapy (SBRT) was used to treat pulmonary metastases. Skull metastasis appeared in March 2024, requiring further local radiotherapy. Despite this, the patient has survived for over 26 months, with a progression-free survival (PFS) of 8 months. CONCLUSIONS HAIC combined with bevacizumab and sintilimab can alleviate primary HCC and tumor thromboses, and further local radiotherapy can control the progression of distant metastases, prolonging the survival time of patients with advanced HCC.

While triplet therapy (HTI), which combines hepatic arterial infusion chemotherapy (HAIC) with tyrosine kinase inhibitors and immune checkpoint inhibitors, is widely used in the treatment of large hepatocellular carcinoma (HCC), there are few reports about its efficacy versus HAIC, and no reliable methods are available for promptly predicting HTI response.

​​Exosomes, as natural intercellular messengers, are gaining prominence as delivery vehicles in nanomedicine, offering a superior alternative to conventional synthetic nanoparticles for cancer therapeutics. Unlike lipid, polymer, or metallic nanoparticles, which often face challenges related to immunogenicity, targeting precision, and off-tumor toxicity, exosomes can effectively encapsulate a diverse range of therapeutic agents while exhibiting low toxicity, favorable pharmacokinetics, and organotropic properties. This review examines recent advancements in exosome bioengineering over the past decade. Innovations such as microfluidics-based platforms, nanoporation, fusogenic hybrids, and genetic engineering have significantly improved loading efficiencies, production scalability, and pharmacokinetics of exosomes. These advancements facilitate tumor-specific cargo delivery, resulting in substantial improvements in retention and efficacy essential for clinical success. Moreover, enhanced biodistribution, targeting, and bioavailability-through strategies such as cell selection, surface modifications, membrane composition alterations, and biomaterial integration-suggests a promising future for exosomes as an ideal nanomedicine delivery platform. We also highlight the translational impact of these strategies through emerging clinical trials. Additionally, we outline a framework for clinical translation that focuses on: cargo selection, organotropic cell sourcing, precision loading methodologies, and route-specific delivery optimization. In summary, this review emphasizes the potential of exosomes to overcome the pharmacokinetic and safety challenges that have long impeded oncology drug development, thus enabling safer and more effective cancer treatments.

For gastric cancer patients, peritoneal metastasis poses a life-threatening risk due to the high incidence of treatment failure and disease recurrence. Conducting additional research aimed at identifying more efficacious strategies is imperative for enhancing treatment outcomes. This study examined the efficacy and safety of systemic chemotherapy plus a PD-1 inhibitor combination with intravenous or intraperitoneal bevacizumab for gastric cancer with peritoneal metastasis.

Peritoneal metastasis (PM) after radical surgery is an important cause of treatment failure in colorectal cancer (CRC). Intraoperative intraperitoneal perfusion chemotherapy may be an effective method for preventing postoperative PM in patients with CRC. This study aimed to explore the safety and feasibility of intraoperatively preventive intraperitoneal perfusion chemotherapy using lobaplatin for CRC.

Prostate cancer (PCa) is a leading malignancy among men and lacks effective treatment, particularly for metastatic stages. Metastasis contributes significantly to cancer morbidity and mortality. Gilteritinib showed anticancer activity against lung and colorectal cancer but has not been thoroughly investigated for its potential in PCa therapy. This study evaluated the anticancer effects of gilteritinib on PCa cell lines (PC3 and DU145) by assessing cytotoxicity, cell proliferation, colony formation, and migration. Mechanistic studies were conducted to determine its impact on the cell cycle, epithelial-to-mesenchymal transition (EMT), and Wnt/β-catenin signaling. Additionally, the mode of cell death was explored, focusing on endoplasmic reticulum (ER) stress and protein ubiquitination. Gilteritinib exhibited dose-dependent cytotoxicity and inhibited PCa cell proliferation, colony formation, and migration. It induced G1 phase cell cycle arrest by downregulating CDK2, CDK4, and cyclin E1. EMT modulation was observed through the suppression of vimentin, N-cadherin, and Twist, along with increased E-cadherin expression. This EMT inhibition correlated with the downregulation of Wnt/β-catenin signaling components. Notably, gilteritinib triggered a non-apoptotic, non-autophagic cell death characterized by cytoplasmic vacuolation, ER stress, and protein ubiquitination, requiring new protein synthesis. This effect was mediated through the activation of the unfolded protein response (UPR) via the PERK pathway. Gilteritinib demonstrates significant anticancer potential in PCa by inducing cell cycle arrest, inhibiting EMT, suppressing Wnt/β-catenin signaling, and triggering a unique mode of cell death via ER stress. These findings highlight gilteritinib as a promising therapeutic candidate for PCa treatment.

Combining radiotherapy with immune checkpoint inhibitors is a promising approach to improve the effectiveness of cancer treatment. However, the success rates of these clinical studies are limited. It is essential to determine the optimal irradiation scheme that maximizes the therapeutic effect by taking into account the balance between the positive and negative effects of radiation on immunity. In this context, we developed a mathematical mechanistic model that simulates (1) the balance between effector and exhausted cytotoxic T-lymphocytes (CTLs), (2) the number of neoantigens released by high-dose irradiation, and (3) the impact of radiation on draining lymph nodes (DLNs) for systemic anti-tumor immunity, and tested whether this mathematic model fits in several animal experiments. Our mechanistic model reproduced the anti-tumor effects of several cancer treatment models for combination therapies with radiation, immune checkpoint inhibitors, and/or a metabolic modulator. Furthermore, this mechanistic model simulated that tumor suppression in distant metastatic foci, known as the abscopal effect, was dysregulated by hypofractionated high-dose irradiation or by the direct radiation exposure on DLN. The mechanistic model successfully reproduced tumor control under various treatment conditions with appropriate parameters, indicating that it may be useful for optimizing immunoradiotherapy prescriptions.

Chemotherapy is an important treatment for glioblastoma (GBM) and a key component of comprehensive GBM therapy. However, the blood-brain barrier (BBB) and complex tumor microenvironment (TME) restrict the diffusion of drugs, which greatly reduces the chemotherapeutic effect on GBM. Single strategies, such as cell-based nanobots to cross the BBB or enzymatic nanobots propelled by enriched substrates in the TME for deep tumor penetration, remain inadequate to address multiple barriers and achieve precise targeting. Here, we develop a Trojan horse-inspired enzymatic nanobot-in-neutrobot system (Trojanbot) to greatly enhance targeted GBM therapy. Trojanbots traverse the BBB by leveraging positive chemotaxis in response to tumor-derived chemokine gradients, after which the released catalase-driven nanobots (CatNbot) undergo directional movement along the H2O2 gradients in TME, facilitating deep tumor penetration. This multi-stage targeting strategy improves drug delivery efficiency, providing considerable potential as a clinical approach for brain tumor treatment.

Local anesthetics promote anticancer immune responses. A machine learning-based algorithm trained with information on the biological effects and molecular descriptors of analgesics, anesthetics, hypnotics and opioids predicted antitumor effects for dexmedetomidine (DEX). DEX is a sedative acting as an alpha2-adrenoceptor (ADRA2) agonist. Based on these premises, we investigated the putative antineoplastic effects of DEX.

Glioblastoma (GBM) is the most malignant primary intracranial tumor. Owing to its unfavorable prognosis and frequent recurrence, patient outcomes are poor even with standard treatment. Recent studies have reported that FTY720, a structurally modified sphingosine extracted from Cordyceps sinensis, has preclinical antitumor efficacy and can regulate the microenvironment of GBM. However, the mechanism and effective utilization of FTY720, i.e., avoiding adverse reactions during systemic application in GBM remain unclear.

The development of targeted drug delivery systems has become a cornerstone of modern cancer therapy which provides a pathway to maximize treatment effectiveness while reducing side effects. Among the plethora of innovative strategies, biotinylated nanoparticles have evolved as a hopeful tool due to their ability to exploit the elevated expression of biotin receptors on cancerous cells. The design, synthesis, and functionalization of biotinylated nanoparticles for cancer treatment are thoroughly examined in this review article. By leveraging biotin's high affinity for biotin receptors, these nanoparticles achieve selective cancerous cell targeting, leading to enhanced drug bioavailability and cellular uptake. The discussion extends to the underlying mechanisms of drug release, receptor-mediated endocytosis, and strategies for achieving endosomal escape or pH-sensitive drug activation. Furthermore, the article also emphasizes how biotinylation in combination therapy allows for synergistic effects with immunomodulators, nucleic acids, and chemotherapeutic drugs. Preclinical studies are examined to underscore the translational potential of these systems. The review concludes by addressing current challenges, including scalability, and potential immunogenicity, while proposing future directions for optimizing biotinylated nanoparticles as a transformative approach in cancer treatment.

Regulating membrane protein abundance through Lysosome Targeting Chimera (LYTAC) holds significant promise in addressing various diseases. However, the precise structural control of LYTAC molecules and how to improve their treatment efficacy remain elusive. In this study, we develop a multifunctional phototriggered LYTAC platform, named PT-LYTAC, to enhance targeted protein degradation using a photoactive bispecific aptamer chimera (PBAC). PBAC is designed with a precise modular approach that integrates an NIR photosensitive molecule into a bispecific aptamer chimera. Taking advantage of the low molecular weight and easy synthesis of the DNA aptamers, PBAC can efficiently transport the therapeutically relevant membrane protein PTK7 to lysosomes for degradation through the lysosomal pathway. Moreover, our investigation reveals that the multifunctional PT-LYTAC platform, enabled by DNA aptamers, promotes protein degradation by modulating cellular autophagy. By the combination of targeted protein degradation and spatiotemporally controllable regulation of intracellular oxidative stress, the function of tumor cells can be significantly inhibited. Under NIR laser irradiation, PT-LYTAC completely suppresses colorectal cancer growth with just one dose and a single laser treatment, all without any apparent side effects. We anticipate that this novel PT-LYTAC will expand the use of DNA-based LYTAC drugs and provide a new dimension for targeted protein degradation.