Search Results (223)

Advances in navigational bronchoscopy, robotic platforms, and intraprocedural imaging have transformed bronchoscopy from a diagnostic modality into a potential therapeutic platform for localized treatment of lung cancer. These developments are particularly relevant for patients who are medically inoperable, have limited pulmonary reserve, or require lung-sparing treatment strategies. This narrative review summarizes current evidence regarding bronchoscopic ablative technologies and intratumoral therapies for lung cancer. We discuss technological foundations including robotic bronchoscopy, electromagnetic and shape-sensing navigation, cone-beam computed tomography, augmented fluoroscopy, and radial endobronchial ultrasound. Available ablative modalities, including radiofrequency ablation, microwave ablation, cryoablation, photodynamic therapy, and pulsed electric field ablation, are reviewed alongside bronchoscopically delivered intratumoral chemotherapy, immunotherapy, and gene-based therapies. Early clinical studies demonstrate high technical success rates and favorable safety profiles for multiple bronchoscopic ablative approaches, with substantially lower rates of pleural complications compared with percutaneous techniques. Intratumoral therapies enable delivery of high local drug concentrations while minimizing systemic toxicity and may enhance antitumor immune responses through modulation of the tumor microenvironment. Emerging evidence suggests potential synergy between local ablation and immunotherapeutic strategies. However, available data remain limited by small sample sizes, heterogeneous treatment protocols, and a lack of randomized comparative studies. Bronchoscopic ablation and intratumoral therapies represent promising additions to the thoracic oncology armamentarium. Continued advances in navigation, imaging, and therapeutic delivery systems are enabling increasingly precise, minimally invasive interventions. Prospective clinical trials are needed to define optimal patient selection, procedural strategies, and integration with surgery, radiation, and systemic therapies within multidisciplinary lung cancer care. Full article

The etiopathogenesis of prostate cancer (PCa) is complex and involves multiple hormonal and environmental factors. Among these, the role of infectious agents remains controversial. Human papillomavirus (HPV) is known to promote carcinogenesis in epithelial tumors and has also been detected, albeit inconsistently, in PCa tissues. This systematic review, meta-analysis, and real-world cohort study aimed to clarify the prevalence and the prognostic role of intratumoral (IT)-HPV detection in locally advanced and metastatic PCa. We performed a systematic literature search including studies reporting IT-HPV detection in locally advanced (LA-PCa) and metastatic PCa (mPCa). Pooled prevalence estimates were calculated using random-effects models. In parallel, HPV DNA was analyzed using archival tissue in a single-center real-world retrospective cohort of 196 metastatic PCa patients. Twenty-three records met the inclusion criteria, comprising 22 full-text publications and one abstract. Nineteen datasets, encompassing 837 patients, contributed to the quantitative synthesis of stage III–IV disease. Pooled IT-HPV prevalence in mPCa was 18.5% (95% CI, 6.4–34%), while including also LA-PCa was 14.6% (95% CI, 5.2–26.8). Eastern countries showed higher IT-HPV prevalence in both mPCa and LA-PCa (40% and 34.3%, respectively) compared with Western regions (0.8% and 0.3%; p < 0.0001). HPV-positive PCa was associated with a higher Gleason score (>7) in advanced stage (pooled OR 6.32, 95% CI, 3.13–12.78) compared with IT-HPV-negative PCa; however, no studies reported data on its association with survival outcomes. Within our retrospective cohort, IT-HPV DNA was detected in 3.1% of cases (6/196) and exhibited typical PCa driver alterations, such as TP53, SPOP, PIK3CA, and AR amplification. IT–HPV seems to be infrequent in metastatic and locally advanced PCa in Western populations and more prevalent in Asian cohorts and might be associated with a higher Gleason score. IT–HPV-positive advanced PCa seems to exhibit typical PCa driver alterations. Data on the association between IT–HPV status and survival outcomes in PCa are lacking. Standardized molecular assays and multicenter prospective studies are needed to delineate its significance in PCa. Full article

Although fixed-size nanoparticles have achieved substantial therapeutic success, a single fixed size may not be optimal for the competing requirements of stability in circulation, tumor accumulation, deep tumor penetration, cellular uptake, and intra-tumoral retention. This review frames this fixed-property limitation as the need to switch structural states in response to successive biological barriers and analyzes original research articles published from 2021 to 2025 on large-to-small transformation, small-to-large transformation and assembly, or multistage assembly-disassembly-reassembly. Rather than treating the stimulus or material as an analytical endpoint, the framework maps each pre-, intermediate-, and post-transition state to its biological site and barrier-specific functions. Direction, intermediate structure, site, sequence, and the temporal characteristics were evaluated together with coupled changes in charge, morphology, stiffness, and surface interactions. Large-to-small transformations generally shift the carrier function from tumor accumulation to penetration or uptake, whereas small-to-large transformations support retention, depot formation, or organelle-localized activity. Multistage systems assign distinct functions to the sequential structural states. However, direct in vivo structural evidence and physiologically relevant kinetic measurements have been limited. Future designs should, therefore, verify that the required structure forms at the intended site and time, and directly connect structural transitions with delivery and therapeutic functions. Full article

TPZ is a hypoxia-activated anticancer agent that exerts selective cytotoxicity within hypoxic tumor microenvironments. Although intratumoral injection of TPZ can achieve localized antitumor activity, the drug is prone to rapid diffusion and clearance from the injection site, limiting its long-term retention and thereby reducing therapeutic durability and overall efficacy. To achieve sustained release and prolonged retention of TPZ in subcutaneous tumors, a thermosensitive nanogel loaded with TPZ (TPZ@PNA-TNG) was developed. By thoroughly mixing 3 mg/mL TPZ with 6 wt% PNA-TNG, the resulting formulation enabled continuous slow release of TPZ following intratumoral injection, resulting in favorable therapeutic outcomes. The sol–gel phase transition behavior of TPZ@PNA-TNG was investigated using the inverted vial method and rheological measurements. In vivo antitumor studies demonstrated that a single administration of TPZ@PNA-TNG effectively suppressed tumor progression, with tumor volume decreasing to 0.72 ± 0.04 times its initial size over a 14-day period. Mechanistically, TPZ@PNA-TNG markedly enhanced antitumor immune responses, inhibited tumor cell proliferation, promoted apoptosis and anti-angiogenesis, and ultimately induced extensive ischemic necrosis within subcutaneous tumors. In addition, owing to the prolonged intratumoral retention capability of PNA-TNG, TPZ@PNA-TNG enabled sustained local delivery of TPZ, thereby significantly reducing systemic toxicity and adverse effects associated with TPZ while maintaining favorable biocompatibility. These findings highlight the therapeutic potential of TPZ@PNA-TNG for cancer therapy applications. Full article

Paclitaxel (PTX) remains a major component of treatment for solid tumors, but its clinical performance is limited by poor aqueous solubility, solvent-associated toxicity, heterogeneous tumor exposure, and multifactorial drug resistance. This narrative review examines PTX nanomedicines from a molecular pharmacology perspective, focusing on how carrier design interacts with resistance pathways, tumor microenvironment signals, and intracellular drug trafficking. We outline resistance mechanisms involving ATP-binding cassette subfamily B member 1 (ABCB1)/P-glycoprotein (P-gp)-mediated efflux, microtubule remodeling, apoptosis-related signaling, epigenetic regulation, extracellular matrix deposition, hypoxia, and redox imbalance. We evaluate albumin-bound formulations, liposomes, polymeric micelles, stimuli-responsive carriers, biomimetic systems, carrier-free prodrug assemblies, and multidrug co-delivery platforms according to the molecular and biological barriers they address. Particular attention is given to pH-, redox-, enzyme-, and hypoxia-responsive release; tissue penetration and subcellular localization; and co-delivery of PTX with chemosensitizers, nucleic acids, or pathway-directed agents. Molecular simulation and machine learning are considered as tools for formulation optimization and biomarker-guided patient stratification. These approaches can coordinate drug exposure and resistance modulation in preclinical models, but clinical benefits remain inconsistent. Translation will require reproducible formulations, clinically predictive models, direct measurement of intratumoral drug levels, and validated biomarkers linking molecular delivery mechanisms to patient outcomes. Full article

Background/Objectives: Combining chemotherapy with local magnetic hyperthermia (MHT) is promising because heating tumor tissue can increase cell damage, sensitize cells to cytostatic drugs, impair DNA repair, and change tumor microenvironment permeability. This creates conditions for enhancing the antitumor efficacy of chemotherapy while potentially reducing systemic toxicity. The aim of this study was to evaluate the efficacy of MHT with Zn_0.2Mn_0.8Fe₂O₄@OA nanoparticles alone and in combination with cisplatin in a Lewis lung carcinoma model. Methods: Four types of magnetic nanoparticles were synthesized and characterized: Fe₃O₄ and Zn_0.2Mn_0.8Fe₂O₄ coated with oleic acid (OA) or SiO₂-NH₂. Their physicochemical and magnetothermal properties, cytotoxicity, reactive oxygen species generation, and biodegradation in vivo were evaluated. Antitumor efficacy was studied in C57Bl/6 mice with LLC tumors after intratumoral administration of nanoparticles and two MHT sessions (100 kHz, 8 kA/m, 30 min). In combination therapy, ZnMn@OA and cisplatin at doses of 9 or 18 mg/kg were used. Results/Conclusions: Zn_0.2Mn_0.8Fe₂O₄@OA combined efficient heating, biodegradation, and the most pronounced effect among the MHT-alone groups, although MHT without chemotherapy did not provide sustained inhibition of tumor growth or a significant increase in survival. The combination of Zn_0.2Mn_0.8Fe₂O₄@OA-MHT with cisplatin 9 mg/kg produced the best therapeutic outcome: median survival increased significantly by two fold compared with the control group and by 1.8-fold compared with the chemotherapy-alone group at the comparable cisplatin dose. This regimen also stabilized body weight, reduced systemic toxicity, and restored RBC, HGB, and HCT parameters to the level of healthy animals by day 7 of the experiment. These data confirm the potential of MHT as a chemosensitizing approach that improves the efficacy and tolerability of cisplatin therapy. Full article

Background: Plant-derived virus-like particles (VLPs) are emerging nanoplatforms for local cancer immunotherapy, yet their relative performance across structurally distinct particles remains insufficiently defined. Methods: We performed a comparative benchmarking study of eleven plant-derived VLPs spanning diverse architectures and functional properties using an integrated workflow of physicochemical characterization, immune-functional profiling, and in vivo evaluation. All VLPs were produced in endotoxin-minimized ClearColi BL21 (DE3), enabling assessment of intrinsic particle-associated immunostimulatory activity with reduced bacterial endotoxin confounding. Results: In vitro, several VLPs stimulated macrophage-associated responses and enhanced tumor cell killing, although classical M1/M2 polarization markers in RAW264.7 cells did not consistently predict functional cytotoxicity. In a subset of candidates, HEK-TLR3 reporter activity varied substantially under RNA-normalized conditions and was not predicted solely by total RNA content or apparent RNA size distribution. Five candidates were advanced to intratumoral evaluation in the male-derived B16-F10 melanoma model, where CCMV-ss and CMVtt showed trends toward reduced tumor progression and increased immune cell infiltration in male mice. Furthermore, host sex-associated differences in baseline immune features were observed, though these must be interpreted with caution given the H-Y antigen-driven immunogenicity inherent to the male-derived B16-F10 model in female hosts. Conclusions: This study establishes a standardized comparative framework linking plant VLP properties with immune-functional performance and identifies CCMV-ss and CMVtt as promising candidates for further development as locally administered cancer immunotherapy nanoplatforms. Full article

Breast cancer treatment still faces challenges including local recurrence, systemic toxicity, tumor heterogeneity, drug resistance, and immunosuppression. Conventional systemic administration provides limited exposure at the tumor site and exhibits significant toxicity. Injectable hydrogels, combining the properties of minimally invasive administration, in situ gelation, local retention, and sustained release, have become a key platform for local precision drug delivery. Compared with nanomedicines or free drugs, hydrogels can both prolong drug retention time and achieve on-demand release through the modulation of crosslinking density, degradation rate, and responsive chemical bonds. This review is organized around the material logic of such systems. Injectable hydrogels are first classified into natural, synthetic, hybrid, supramolecular, nanocomposite, and self-healing systems, the in situ gelation chemistries available to each are compared, and network parameters such as crosslinking density, mesh size, swelling, porosity, modulus, and rheology are related to release kinetics and intratumoral retention. Current research is primarily advancing along two directions: one is the construction of pH-, enzyme-, redox/ROS-, hypoxia-, ATP-, glucose-or thermo-responsive hydrogels; the other is achieving active targeting by integrating functionalized hydrogels with targets such as CD44, folate receptor, integrins, EGFR, transferrin receptor, and HER2 or with biomimetic cell-membrane coatings. On this basis, hydrogels have been extended to cancer vaccines, immune checkpoint modulation, local delivery of CAR-T/CAR-NK, as well as combination therapies involving chemotherapy, photothermal therapy, photodynamic therapy, chemodynamic therapy, sonodynamic therapy, radiosensitization, gene therapy, and theranostics. The constraints imposed on hydrogel design by different payload classes, including small molecules, natural products, proteins and peptides, nucleic acids, antibodies, exosomes, and gene-editing machinery, are further examined, and imaging-integrated theranostic gels are discussed together with the emerging role of machine learning and digital fabrication in hydrogel optimization. Based on the biological foundations of breast cancer, this review summarizes advances in the material design, microenvironment-responsive release, targeting strategies, immunomodulation, and combination therapy of hydrogels, critically evaluates the limitations of each strategy, and aims to provide a reference for the design of mechanistically well-defined and translatable hydrogel delivery systems for breast cancer. Full article

Breast cancer remains a leading cause of cancer-related mortality worldwide, highlighting the need for novel therapeutic strategies that selectively target tumor cells while minimizing systemic toxicity. Dietary ammonium hydroxide enhancement (AHE) has previously been shown to modulate metabolic pathways in animal studies. However, its potential as a localized anticancer therapy has not been investigated. In the present study, we evaluated the antitumor efficacy and systemic safety of NH₄OH using complementary in vitro and orthotopic breast cancer xenograft models. MDA-MB-231 breast cancer cells and non-tumorigenic MCF10A mammary epithelial cells were treated with increasing concentrations of NH₄OH (2.5–225 µM) to assess dose-dependent effects on cell proliferation, viability, and apoptosis. Following this, MDA-MB-231 cells were orthotopically xenografted into female athymic nude mice and treated by intratumoral injection with NH₄OH using a stepwise dose-escalation regimen (0.01%, 0.1%, and 0.5%; total volume of 20 μL per tumor divided between two injection sites) or phosphate-buffered saline (PBS). Differences between treatment groups of mammary tumors and kidney tissues were analyzed molecularly and histologically. NH₄OH significantly suppressed MDA-MB-231 cell growth and metabolic activity, with minimal effects on MCF10A cells, and induced apoptosis in MDA-MB-231 cells without detectable apoptotic induction in MCF10A cells. In vivo, although tumor volume only showed a non-significant downward trend, histological and molecular analyses demonstrated substantial alterations in tumor biology. NH₄OH treatment induced molecular changes consistent with an antitumor response, including increased Caspase-3 and p53 expression, reduced BCL2 and Ki-67 expression, and attenuation of TNFα, IL-6, and TLR4 inflammatory signaling. Furthermore, the tumor architecture in T-NH tumors displayed increased pale eosinophilic regions and reduced cellular density, suggestive of treatment-associated tumor tissue disruption. Histological analysis of kidney tissue showed no evidence of overt renal toxicity. Indeed, localized NH₄OH administration was associated with reduced renal inflammatory and apoptotic signaling, preserved renal morphology, and increased expression of the ammonia transporters RHBG and RHCG. Cross-sectional morphometric measurements showed decreased area for the distal convoluted tubules in NH₄OH-treated samples. Although this initial preclinical study was limited by a relatively small sample size, further studies are warranted to validate these findings and define the molecular mechanisms underlying NH₄OH-mediated antitumor activity. Collectively, these findings suggest that intratumoral NH₄OH modulates tumor metabolic, inflammatory, and apoptotic pathways associated with a less aggressive tumor phenotype while showing no overt molecular or histological evidence of renal injury, supporting further investigation as a localized metabolic intervention targeting molecular and histological drivers of breast cancer progression. Full article

Background/Objectives: Glioblastoma (GBM) remains one of the most aggressive primary brain malignancies, with limited therapeutic progress over the past two decades. Systemic administration of temozolomide (TMZ) is a pillar of clinical management but is constrained by poor brain penetration, short half-life, and systemic toxicity. Localized drug delivery systems represent a compelling approach to address these limitations. We report the development and evaluation of an injectable poly(sebacic acid–ricinoleic acid) poly(anhydride-ester) (pSARA) gel for sustained intratumoral delivery of TMZ. Methods: The pSARA gel was synthesized using a one-pot melt polycondensation technique, and its in vitro release dynamics were assessed using spectrophotometry. In vivo efficacy of the TMZ-loaded pSARA gel was evaluated as a monotherapy and as an adjuvant to radiation or surgical resection using an orthotopic 9L gliosarcoma rat model. Results: The formulation exhibits shear-thinning behavior, enabling syringe-based administration, and undergoes surface erosion in aqueous environments to achieve controlled drug release. In vivo, the TMZ-loaded pSARA significantly prolonged survival compared to controls and outperformed paclitaxel-loaded formulations. Furthermore, combination therapy with radiation or surgical resection demonstrated combined survival benefits, including long-term survivors. Conclusions: These findings highlight the translational potential of pSARA-based local delivery systems as an adjunct or alternative to systemic chemotherapy in GBM treatment. Full article

Prostate cancer remains one of the most frequently diagnosed malignancies in men worldwide, and despite favorable outcomes for localized disease, progression to castration-resistant prostate cancer (CRPC) represents a major clinical challenge associated with poor prognosis. CRPC is characterized by disease progression despite castrate levels of circulating testosterone and is most commonly diagnosed in the metastatic setting. Although the introduction of second-generation androgen receptor-targeted therapies has improved survival, resistance inevitably emerges. This review overviews the most recent findings in the field of CRPC with particular emphasis on the current understanding of the biological mechanisms of hormone-resistant cancer as well as the evidence on treatment strategies. A comprehensive literature search was conducted across PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar, focusing mainly on studies published between 2015 and 2025 that investigated molecular and cellular mechanisms of resistance to androgen deprivation therapy and androgen receptor (AR)-targeted treatments. Seventy-eight relevant articles were included in the final synthesis. The reviewed evidence highlights four major categories of resistance mechanisms. First, AR-dependent alterations remain predominant, including AR gene amplification, activating mutations, dysregulation of co-regulators, and expression of constitutively active AR splice variants such as androgen receptor variant 7 (AR-V7). Second, AR-independent or bypass pathways, most notably phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR), wingless-related integration site (WNT)/β-catenin, mitogen-activated protein kinase (MAPK), and glucocorticoid receptor signaling, enable tumor survival despite AR blockade. Third, lineage plasticity and transdifferentiation to neuroendocrine prostate cancer represent a distinct and increasingly recognized resistance mechanism driven by loss of tumor protein 53 (TP53) and retinoblastoma 1 (RB1) and epigenetic reprogramming. Finally, additional contributors, including intratumoral androgen synthesis, metabolic reprogramming, and tumor microenvironment interactions, further support disease progression. Together, these interconnected mechanisms underscore the biological complexity of CRPC and emphasize the need for biomarker-guided, combination-based therapeutic strategies to overcome resistance and improve patient outcomes. Full article

Lung cancer remains the leading cause of cancer-related mortality worldwide, and durable benefit from immune checkpoint inhibitors is limited by immune exclusion, microenvironmental immunosuppression, and toxicity. This narrative translational review evaluates whether endobronchial intratumoral delivery of immuno- and gene-based therapies can transform bronchoscopic access into a therapeutic platform linking local tumour intervention with systemic antitumour immunity. We synthesise evidence on endobronchial ultrasound, electromagnetic navigation bronchoscopy, and robotic-assisted bronchoscopy, together with local checkpoint blockade, cytokine and mRNA-lipid nanoparticle constructs, oncolytic virotherapy, dendritic-cell approaches, viral and non-viral gene transfer, and enzyme- or metabolite-based strategies. Current clinical evidence remains preliminary, consisting mainly of Phase I trials, small prospective cohorts, and case-based signals, with feasibility and safety observations but no completed randomised trial demonstrating efficacy against standard-of-care systemic therapy. The most plausible candidates are patients with advanced or recurrent NSCLC, bronchoscopically accessible lesions, inadequate response to systemic immunotherapy, and immune-excluded or locally immunosuppressed tumours. Biomarkers such as PD-L1, tumour mutational burden, CD8+ infiltration, tertiary lymphoid structures, radiomics, and circulating tumour DNA require validation. This review integrates delivery technology, immune mechanisms, statistical evidence appraisal, biomarker limitations, AI-guided planning, and global feasibility. Full article

Background/Objectives: Magnetotactic bacteria therapy is an emerging active intratumoral drug delivery platform in which drug-loaded, magnetically responsive bacteria are injected into a tumor and navigated through its microenvironment toward defined targets using an external magnetic field, fundamentally distinct from passive intratumoral injection. No endoscopic ultrasound (EUS)- or ultrasound (US)-guided delivery workflow for MTBT has been described, and five critical technical prerequisites for clinical translation remain unaddressed: three-body image registration, minimum contrast concentration for cone-beam computed tomography (CBCT) bolus localization, needle repositioning accuracy, optimal fiducial strategy, and EUS/US procedural feasibility within the magnetic guidance apparatus. Methods: In three healthy female swine, we tested an image-guided intratumoral workflow at pancreatic and rectal sites. Gold rod fiducials were implanted under EUS in two animals and via transabdominal/endorectal US in one animal. A needle was navigated toward the implanted fiducial group using real-time gold-fiducial shine-through, and 2 mL of saline mixed with iodine contrast (Isovue-370) at 15%, 10%, or 5% v/v (one concentration per animal) was injected. Scan with CBCT was acquired before and after injection; fiducials, needle tip, and contrast bolus were segmented in 3D Slicer and their centroids compared to quantify targeting accuracy. Contrast visibility and artifact were scored by an expert radiologist on a five-point Likert scale. EUS feasibility within the magnetic apparatus was assessed using a full-scale cardboard replica of the CuraDrone PolarTrak. Results: Five percent v/v Isovue-370 was the minimum concentration for reliable CBCT bolus identification (280–360 HU; 1:1 injection-to-volume ratio). Needle repositioning accuracy was ≤2 cm in 5/6 sites using fiducial shine-through guidance. Gold rod fiducials served a dual role: CBCT tumor registration and real-time EUS/US navigation, not previously described for intratumoral injection. EUS was feasible within the PolarTrak with defined workflow adaptations. Conclusions: This pilot study demonstrates the technical feasibility of an EUS/US–CBCT workflow for MTBT, yielding quantitative, actionable parameters for first-in-human trial design. These feasibility findings, obtained in a small healthy animal cohort, are intended to inform the design of subsequent clinical studies. Full article

Gynecological malignancies and breast cancer impose substantial health and economic burdens. This review examines how local and systemic microbiota may affect epithelial integrity, inflammation, estrogen metabolism, and immunity. The vaginal ecosystem is the most extensively studied female microbial niche. Cervical cancer serves as the most illustrative clinical example: loss of stable Lactobacillus crispatus dominance and increased prevalence of anaerobic bacteria (anaerobic dysbiosis) are associated with persistent HPV infection, which directly elevates the risk of cervical precancerous lesions. The estrobolome is particularly relevant in endometrial cancer, where intestinal bacterial beta-glucuronidase activity may increase estrogen reabsorption, particularly in obesity and metabolic disease. In ovarian cancer, microbiota is being studied as a possible risk modifier in BRCA1 carriers, but the evidence remains exploratory. In breast cancer, intratumoral bacteria may shape the immune microenvironment, particularly in triple-negative disease. The primary limitation of current research is methodological heterogeneity. Low-biomass samples, such as those from the ovary or endometrium, are highly susceptible to technical contamination. Most studies are cross-sectional and cannot establish causality. Current evidence supports microbiota as a modifier, not a standalone marker or a substitute for standard diagnosis and treatment. Its most plausible near-term role is in multiparameter risk or response models, pending standardized prospective validation. Full article

Background: Local drug delivery can increase antitumor exposure while limiting systemic toxicity, but chemotherapy-only local treatment may not fully control residual tumor growth in immunosuppressive tumor microenvironments. This study aimed to develop and preliminarily evaluate ffky-antiCD3, a CD3-recognition peptide-functionalized self-assembling peptide platform for intratumoral doxorubicin (DOX) delivery. Methods: The Nap aromatic group in a previous Nap-ffky scaffold was removed to improve aqueous dispersibility, and the CD3-recognition sequence AKMGEGGWGANDY was introduced to generate ffky-antiCD3. The peptide/formulation was characterized by reversed-phase high-performance liquid chromatography, mass spectrometry, TEM, circular dichroism spectroscopy, and a preliminary in vitro DOX release assay under tumor-mimicking acidic conditions. Antitumor efficacy, tumor histopathology, image-based CD3/CD8 semi-quantification, splenic IFN-γ levels, serum biochemistry, organ coefficients, and major-organ histology were assessed after repeated intratumoral treatment in B16-F10 melanoma-bearing C57BL/6 mice. Results: ffky-antiCD3 formed assemblies with a β-sheet-rich secondary structure. TEM observation further showed heterogeneous irregular/network-like supramolecular assemblies, and the preliminary release assay suggested slower apparent DOX release from ffky-antiCD3/DOX than from free DOX at pH 6.5. Among the tested groups, ffky-antiCD3/DOX produced the strongest short-term tumor-growth inhibition and the lowest endpoint tumor weight during the 10-day observation period. Ki67 staining decreased, and TUNEL signals increased after ffky-antiCD3/DOX treatment, supporting reduced proliferation and enhanced apoptosis-related damage. CD3/CD8 staining and exploratory splenic IFN-γ measurements indicated preliminary immune-related changes associated with ffky-antiCD3-containing formulations. Body weight, organ weights, serum biochemical markers, and major-organ H&E staining revealed no obvious short-term toxicity signals under the tested regimen. Conclusions: ffky-antiCD3/DOX represents a candidate local peptide-based chemo-immunomodulatory formulation. Its immune mechanism, release behavior, biodistribution, and long-term efficacy and safety require further validation before strong mechanistic or translational claims are made. Full article