Tumor Site Research Articles

Size-switchable and dual-targeting nanomedicine for cancer chemoimmunotherapy by potentiating deep tumor penetration and antitumor immunity

The effectiveness of commonly adopted therapeutic regimen is low for treating triple-negative breast cancer (TNBC), especially for inoperable patients at advanced stage. Herein, we reported a nano-based recipe for orthotopic and metastatic TNBC management by potentiating the deep penetration of antitumor agents in solid tumors and remodeling the tumor immune microenvironment through combinational chemoimmunotherapy. Specifically, doxorubicin (DOX) was loaded in DSPE-PEG2000-modified poly(amidoamine) (PAMAM) dendrimer to obtain small-sized DOX@P nanoparticles, which were further inserted into the phospholipid monolayer of imiquimod (R837)-encapsulated reconstituted high-density lipoprotein (rHDL) to acquire R@rHDP. Finally, M2 macrophage-targeting peptide (M2pep) was modified on the surface of R@rHDP to obtain R@rHDP-M2pep nanoparticles with special targeting ability towards M2-like tumor-associated macrophages (TAMs). Upon intravenous injection, R@rHDP-M2pep actively anchored TNBC sites owing to the natural tumor targeting potential of rHDL. Once reaching tumor sites, small-sized DOX@P was released from large-sized R@rHDP-M2pep due to the breakdown of imine bond in acidic tumor microenvironment (TME), further carrying DOX into the deep tumor core to exert chemotherapeutic effect. On the other hand, the remaining R@rH-M2pep continued to target M2-like TAMs to deliver R837 for effective polarization of TAM phenotype from protumoral M2-like into antitumoral M1-like type. Consequently, the immunosuppressive TME was remodeled to facilitate improved immunotherapeutic performance. Hence, the designed R@rHDP-M2pep nanoparticles displayed potent antitumor efficacy against TNBC, which not only remarkably suppressed orthotopic tumor growth, but also prevented the lethal lung metastasis of TNBC, largely prolonging the survival time of mice suffered from TNBC. Altogether, the proposed strategy exhibited promising research value in advancing the therapeutic protocols for TNBC.

Predictors and surgical outcome of hemorrhagic metastatic brain malignancies.

Intracerebral metastases present a substantial risk of tumor-associated intracerebral hemorrhage (ICH). This study aimed to investigate the risk of hemorrhagic events in brain metastases (BM) from various primary tumor sites and evaluate the safety and outcomes of surgical tumor removal. A retrospective, single-center review of medical records was conducted for patients who underwent BM removal between January 2016 and December 2017. Patients with hemorrhagic BM were compared to those with non-hemorrhagic BM. Data on preoperative predictors, perioperative management, and postoperative outcomes were collected and analyzed. A total of 229 patients met the inclusion criteria. Melanoma metastases were significantly associated with preoperative hemorrhage, even after adjusting for confounding factors (p = 0.001). Poor clinical status (p = 0.001), larger tumor volume (p = 0.020), and unfavorable prognosis (p = 0.001) independently predicted spontaneous hemorrhage. Importantly, preoperative use of anticoagulant medications was not linked to increased hemorrhagic risk (p = 0.592). Surgical removal of hemorrhagic BM, following cessation of blood-thinning medication, did not significantly affect intraoperative blood loss, surgical duration, or postoperative rebleeding risk (p > 0.096). However, intra-tumoral hemorrhage was associated with reduced overall survival (p = 0.001). This study emphasizes the safety of anticoagulation in patients with BM and highlights the safety of neurosurgical treatment in patients with hemorrhagic BM when blood-thinning medication is temporarily paused. The presence of intra-tumoral hemorrhage negatively impacts survival, highlighting its prognostic significance in BM patients. Further research with larger cohorts is warranted to validate these findings and elucidate underlying mechanisms.

Neutral Cyanine: Ultra-Stable NIR-II Merocyanines for Highly Efficient Bioimaging and Tumor-Targeted Phototheranostics.

Fluorescence imaging (FLI)-guided phototheranostics using emission from the second near-infrared (NIR-II) window show significant potential for cancer diagnosis and treatment. Clinical imaging-used polymethine ionic indocyanine green (ICG) dye is widely adopted for NIR fluorescence imaging-guided photothermal therapy (PTT) research due to its exceptional photophysical properties. However, ICG has limitations such as poor photostability, low photothermal conversion efficiency (PCE), short-wavelength emission peak, and liver-targeting issues, which restrict its wider use. In this study, two ionic ICG derivatives are transformed into neutral merocyanines (mCy) to achieve much-enhanced performance for NIR-II cancer phototheranostics. Initial designs of two ionic dyes show similar drawbacks as ICG in terms of poor photostability and low photothermal performance. One of the modified neutral molecules, mCy890, shows significantly improved stability, an emission peak over 1000nm, and a high photothermal PCE of 51%, all considerably outperform ICG. In vivo studies demonstrate that nanoparticles of the mCy890 can effectively accumulate at the tumor sites for cancer photothermal therapy guided by NIR-II fluorescence imaging. This research provides valuable insights into the development of neutral merocyanines for enhanced cancer phototheranostics.

Degradable tumor-specific H2S nanogenerators for disrupting tumor metabolic symbiosis and activating anti-tumor immune responses

The design of highly efficacious nanotherapeutic agents that target tumors and degrade in specific response is of great relevance and developmental promise. We have designed a tumor-specific decomposable H2S nanogenerator for the purpose of safely and effectively disrupting tumor metabolic symbiosis and activating anti-tumor immune responses. Dendritic mesoporous organosilica doped with Mn2+ (DMOM) was used as a H2S donor that could be specifically degraded in response to glutathione (GSH), and then α-Cyano-4-hydroxycinnamic acid (CHC, a monocarboxylate transporter protein inhibitor) was loaded on the pores and surface of the organosilica through a condensation reaction, and further modified with hyaluronic acid (HA). The H2S nanogenerator could target the tumor site and undergo continuous self-degradation, releasing doped Mn2+ and loaded CHC while depleting GSH and generating large amounts of H2S, which could ultimately destroy lactate metabolic symbiosis, induce multiple acidosis in tumor cells, reduce intracellular adenosine triphosphate (ATP) and enhance chemodynamic therapy. More importantly, both the H2S produced and the inhibition of lactate efflux could have an immunomodulatory effect and exert a positive influence on the activation of the immune system. Therefore, the tumor-specific degradable H2S nanogenerator with diverse therapeutic functions introduced in this work is expected to provide a new idea and a new paradigm for efficient anti-tumor therapy.

Emergency department involvement in the diagnosis of cancer among older adults: a SEER-Medicare study.

Internationally, 20% to 50% of cancer is diagnosed through emergency presentation, which is associated with lower survival, poor patient experience, and socioeconomic disparities, but population-based evidence about emergency diagnosis in the United States is limited. We estimated emergency department (ED) involvement in the diagnosis of cancer in a nationally representative population of older US adults, and its association with sociodemographic, clinical, and tumor characteristics. We analyzed Surveillance, Epidemiology, and End Results Program-Medicare data for Medicare beneficiaries (≥66 years old) with a diagnosis of female breast, colorectal, lung, and prostate cancers (2008-2017), defining their earliest cancer-related claim as their index date, and patients who visited the ED 0 to 30 days before their index date to have "ED involvement" in their diagnosis, with stratification as 0 to 7 or 8 to 30 days. We estimated covariate-adjusted associations of patient age, sex, race and ethnicity, marital status, comorbidity score, tumor stage, year of diagnosis, rurality, and census-tract poverty with ED involvement using modified Poisson regression. Among 614 748 patients, 23% had ED involvement, with 18% visiting the ED in the 0 to 7 days before their index date. This rate varied greatly by tumor site, with breast cancer at 8%, colorectal cancer at 39%, lung cancer at 40%, and prostate cancer at 7%. In adjusted models, older age, female sex, non-Hispanic Black and Native Hawaiian or Other Pacific Islander race, being unmarried, recent year of diagnosis, later-stage disease, comorbidities, and poverty were associated with ED involvement. The ED may be involved in the initial identification of cancer for 1 in 5 patients. Earlier, system-level identification of cancer in non-ED settings should be prioritized, especially among underserved populations.

Cardiac tumors with life threatening arrhythmia, an eight year single centre experience

Abstract Background Cardiac tumors are rare cardiac disorders which occur either as primary or secondary tumors. They have a wide variety of clinical presentations from accidental discovery till sudden cardiac death. Manifestations are mainly due to mass effect, local invasion, embolization, or constitutional symptoms. (1) Cardiac tumor related arrhythmias are more often incessant, especially in younger children, and the mechanism can be reentry or triggered automaticity. (2) Arrhythmia management depends on its clinical impact as well as tumor size, site, and nature. Surgical resection is preferred in life threating arrhythmias however, the decision should be tailored. Purpose To describe our institution’s tailored approach in treatment of cardiac tumors presenting with life threatening ventricular arrhythmias (VAs), including surgical resection, coiling of feeding vessels or even ICD implantation with long term rhythm monitoring. Methods We reviewed patients with primary cardiac tumors presenting to our center from 2015 to 2023 with emphasis on those with life threatening VAs. Patient records were examined for clinical presentation, ECGs, imaging modalities, histopathological analysis of the resected tumors and interrogation data for those with cardiac implantable electronic devices (CIEDS). Results Over 8 years, 64 patients were diagnosed to have primary cardiac tumors. Of those, 3.8% (6 patients) presented with life threatening monomorphic VT, half of them were pediatrics. Tissue characterization by CMR and histopathological analysis for the resected tumors revealed: 4 fibromas, one lipoma and one hemangioma. Surface ECGs during VT showed exit at, or close to, the site of the tumor (Table). Total surgical resection was performed in four cases (3 fibromas and one lipoma), one of them (the youngest, 6 months old) died during the postoperative period due to refractory heart failure. Partial resection was done in one patient with fibroma as the tumor involved the majority of RV free wall while the patient with hemangioma underwent coiling of the feeding vessels twice with marked decrease in the tumor size however he had one further episode of VT, so ICD was implanted. Over a mean follow up period of 3 years, four patients had no recurrence of tachycardia as confirmed with implantable loop recorders (ILRs) while the patient with ICD had infrequent episodes. Conclusion Total surgical resection, albeit risky, is highly effective in eliminating life threatening VAs caused by cardiac tumors. Other modalities like partial resection or coiling of the feeding vessels could be effective in high-risk patients. Devascularization, in our hemangioma case was not totally protective. Finally, ILRs were highly beneficial in confirming long-term freedom of arrhythmia after resection.Table: VT exit, tumor site and typeECG, CMR, angiogram& surgical view

Intratumoral antigen signaling traps CD8+ T cells to confine exhaustion to the tumor site.

Immunotherapy advances have been hindered by difficulties in tracking the behaviors of lymphocytes after antigen signaling. Here, we assessed the behavior of T cells active within tumors through the development of the antigen receptor signaling reporter (AgRSR) mouse, fate-mapping lymphocytes responding to antigens at specific times and locations. Contrary to reports describing the ready egress of T cells out of the tumor, we find that intratumoral antigen signaling traps CD8+ T cells in the tumor. These clonal populations expand and become increasingly exhausted over time. By contrast, antigen-signaled regulatory T cell (Treg) clonal populations readily recirculate out of the tumor. Consequently, intratumoral antigen signaling acts as a gatekeeper to compartmentalize CD8+ T cell responses, even within the same clonotype, thus enabling exhausted T cells to remain confined to a specific tumor tissue site.

Self-reported exhaustion and a 4-item physical frailty index to predict the incidence of major complications after onco-geriatric surgery

BackgroundThe aim of this study was to analyze four pre-operative physical frailty indicators from a geriatric assessment (GA) independently and combined in a physical frailty index, in their ability to predict postoperative 30 d-complications. Materials and methodsIn this secondary analysis of data from the published PERATECS study (ClinicalTrials.gov: NCT01278537), the predictive value of four physical frailty indicators from a defined GA battery was examined with univariable and multivariate logistic regression models in a sample of 493 onco-geriatric surgical patients. The primary endpoint was incidence of major (Clavien–Dindo ≥ grade 2 [CD ≥ 2]) complications within 30 postoperative days.Predictors of the first model included self-reported exhaustion (SRE), body mass index (BMI), Timed Up-and-Go (TUG) and handgrip strength (HGS) independently, and a second model combined these four items as a Physical Frailty Index (4i-PFI). Both regression models were adjusted for age, gender, American Society of Anesthesiologists (ASA) status, tumor sites, duration of surgery time and Mini Nutritional Assessment (MNA) score. ResultsA total of 233 patients (47 %) developed CD ≥ 2 complications. In addition to ASA score, length of surgery, and gynecological and upper gastrointestinal tumor sites, the first model showed that SRE (OR 1.866) predicted CD ≥ 2 complications, but not TUG, BMI and HGS. In the second model, the 4i-PFI predicted CD ≥ 2 complications (OR pre-frail = 1.808, frail = 3.787). ConclusionsPhysical frailty indicators as SRE revealed a better ability to predict CD ≥ 2 complications than BMI, TUG and HGS. However, prediction of CD ≥ 2 complications was enhanced when these parameters were combined in a novel 4i-PFI.

Changes in expression of breast cancer tumor biomarkers between primary tumors and corresponding metastatic sites: common patterns and relationships with survival.

In metastatic breast cancer, differences in expression patterns of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) between the primary tumor (PT) and metastatic site (MET) have been reported. However, there is limited understanding of the relationship of tumor subtype discordance and overall survival (OS). We evaluated patterns of ER/PR/HER2 in PTs and corresponding METs and assessed the relationship between these patterns and OS. Patients diagnosed at our center with metastatic breast cancer (2011-2020) were included. ER/PR were stratified as < 1%/1-10%/ > 10% by immunohistochemistry and HER2 as positive/negative by immunohistochemistry/FISH. Tumor subtypes were classified as ER or PR + /HER2-, HER2+ , or triple-negative. Biomarker discordance data from PTs to METs were analyzed for expression patterns. OS was assessed. Of 254 patients, 41 (16.1%) had synchronous and 213 (83.9%) had metachronous METs. Category change of ER/PR/HER2 expression was observed in 56 (22.0%), 117 (40.5%), and 30 (11.8%) patients, respectively. Tumor subtype changed in 56 (22.0%) patients. We identified a difference between PT and MET from ER > 10% to ER < 1% (n = 28,16.2% p < 0.01); PR > 10% to PR < 1% (n = 54,48.2%, p < 0.001); PR > 10% to PR 1-10% (n = 18,16.1%, p < 0.001), and ER or PR+/HER2-to triple-negative (n = 19,13.0%, p = 0.03). In log-rank analysis, change from an ER or PR+/HER2-(5-year OS 88.6%) PT to a HER2+(67.5%) or triple-negative (54.6%) MET was associated with decreased survival (p < 0.01); however, in multivariate analysis, discordant biomarker expression was not associated with decreased survival (p > 0.05). Tumor expression of ER/PR/HER2 can differ between the PT and MET. Loss of ER/PR expression is common and may be related to worse survival. Routine assessment of MET tumor markers could inform prognosis and therapeutic decision-making.

Hypoxia-Responsive Hydrogen-Bonded Organic Framework-Mediated Protein Delivery for Cancer Therapy.

The efficient delivery of therapeutic proteins to tumor sites is a promising cancer treatment modality. Hydrogen-bonded organic frameworks (HOFs) are successfully used for the protective encapsulation of proteins; however, easy precipitation and lack of controlled release of existing HOFs limit their further application for protein delivery in vivo. Here, a hypoxia-responsive HOF, self-assembled from azobenzenedicarboxylate/polyethylene glycol-conjugated azobenzenedicarboxylate and tetrakis(4-amidiniumphenyl)methane through charge-assisted hydrogen-bonding, is developed for systemic protein delivery to tumor cells. The newly generated HOF platform efficiently encapsulates representative cytochrome C, demonstrating good dispersibility under physiological conditions. Moreover, it can respond to overexpressed reductases in the cytoplasm under hypoxic conditions, inducing fast intracellular protein release to exert therapeutic effects. The strategy presented herein can be applied to other therapeutic proteins and can be expanded to encompass more intrinsic tumor microenvironment stimuli. This offers a novel avenue for utilizing HOFs in protein-based cancer therapy.

Targeted variant prevalence of FBXW7 gene mutation in colorectal carcinoma propagation. The first systematic review and meta-analysis

FBXW7 is a tumour suppressor gene that functions as E3-ubiquitin-ligase, targeting numerous oncoproteins for degradation, i.e., Cyclin-E, c-Myc, and Notch. FBXW7 performs a pivotal role in regulating cell cycle progression. FBXW7 mutation is frequently implicated in various cancers. MethodologyA systematic review and meta-analysis done on several studies using “Preferred Reporting Items for Systemmatic Reviews and Meta-Analysis (PRISMA)” criteria and registered with PROSPERO (registration-number-CRD42023388845). The preliminary search comprises 1182 articles; however, 58 studies were subsequently chosen after eliminating non-eligible studies. To explore the prevalence of FBXW7 mutation among colorectal cancer patients, data were analysed using “OpenMeta Analyst and comprehensive meta-analysis-3.0 (CMA-3.0)” software. ResultsThis meta-analysis involves 13,974 respondents; most were males 7825/13,974, (56.0 %). Overall prevalence of FBXW7 mutations was 10.3 %, (95%CI: 8.6–12.4), I2 = 90.5 %, (P < 0.001). The occurrence of FBXW7 mutations was highest in Russia [19.0 %, (95%CI: 9.8–33.7)] and Taiwan [18.8 %, (95%CI: 8.7–35.9)], P-values< 0.05 while the least prevalence was reported in Netherland (4 %) and Italy (5 %), both P-values< 0.001. Overall prevalence of FBXW7 abberation was greatest amongst male gender: “53.9 %, (95%CI: 8.3–62.0 %)”, Tumour location (colon): 59.8 %, (95%CI: 53.9–65), tumour site (left): 61.6 %, (95%CI: 53.8–68.9), Tumour-grade (Moderate): 65.9 %, (95%CI: 54.9–75.4 %), and Tumour late-stage: 67.9 %, (95%CI: 49.7–84.3 %), all P-values< 0.001. When stratified according to study-period, an increasing trend was noted from 2018 till present with the highest mutation rate recorded in 2022 (15.3 %). ConclusionOverall prevalence of FBXW7 mutations was 10.3 % with male gender, left side, and late-stage being most mutated, and these outcomes conform with severally published articles on FBXW7 mutation.

Energy-storing DNA-based hydrogel remodels tumor microenvironments for laser-free photodynamic immunotherapy

Photodynamic therapy (PDT) is a promising modality for cancer treatment. However, limited tissue penetration of external radiation and complicated tumor microenvironments (TMEs) restrict the antitumor efficiency of PDT. Herein, we report an energy-storing DNA-based hydrogel, which enables tumor-selective PDT without external radiation and regulates TMEs to achieve boosted PDT-mediated tumor immunotherapy. The system is constructed with two ultralong single-stranded DNA chains, which programmed partial complementary sequences and repeated G-quadruplex forming AS1411 aptamer for photosensitizer loading via hydrophobic interactions and π-π stacking. Then, energy-storing persistent luminescent nanoparticles are incorporated to sensitize PDT selectively at tumor site without external irradiation, generating tumor antigen to agitate antitumor immune response. The system catalytically generates O2 to alleviate hypoxia and releases inhibitors to reverse the IDO-related immunosuppression, synergistically remodeling the TMEs. In the mouse model of breast cancer, this hydrogel shows a remarkable tumor suppression rate of 78.3 %. Our study represents a new paradigm of photodynamic immunotherapy against cancer by combining laser-free fashion and TMEs remodeling.

Tracheostomy stomal seeding following tongue cancer resection: A case report

AbstractBackgroundThe tracheostomy site seeding following oral cancer surgery is extremely rare and carries poor prognosis.Case PresentationWe present the case of the 62‐year‐old man with clinical T4bN2bM0 tongue squamous cell carcinoma (SCC). The tracheostomy was planned before cancer resection under general anesthesia, but oral intubation was not possible because of bleeding from tongue cancer. Thus, tracheostomy was performed under local anesthesia. He underwent a total glossectomy with segmental mandibulotomy, bilateral neck dissection with rectus abdominis muscle free flap reconstruction and postoperative radiotherapy. The pathological diagnosis was SCC (pT4bN0M0) with close margin. He underwent adjuvant radiotherapy of 66 Gy that targeted the primary tumor site and upper neck. The mass at the tracheostomy site from seeding was detected 4 months after surgery and treated with 60 Gy of radiotherapy. The patient was died from bleeding and airway obstruction about 7 months from detection of the seeding of tracheostomy site.ConclusionTracheostomy site seeding after temporally tracheostomy for oral cancer is very rare. The pathological mechanisms suspected the tumor seeding. The prognosis of the seeding of tracheostomy site was extremely poor. Possible method to prevent these includes awake tracheostomy without oral intubation for predicting bleeding from bulky tumor with trismus.

Luminescent nanotherapeutics system for Real-Time imaging and Membrane-Mitochondria stepwise targeted drug delivery in ovarian cancer

Considerable attention has been devoted to developing anti-cancer treatments targeted mitochondria. However, there is a dearth of literature on using luminescent metal–organic frameworks for the transportation of anti-cancer drugs to organelles. A luminescent nanotherapeutic platform known as UiO-DOX@FA/TPP has been engineered with a membrane-mitochondrial stepwise targeting strategy for the delivery of doxorubicin (DOX). DOX administration caused mitochondrial dysfunction, increased Caspase-3 activity, and cell apoptosis. The UiO-DOX@FA/TPP system improved drug sensitivity, requiring only 10.8 % of the free DOX dose. It showed strong anti-tumor effects in vivo, with over 98 % tumor growth inhibition and commendable biocompatibility. The system also enabled in vivo imaging by emitting fluorescence at around 500 nm, highlighting its transport and targeted distribution to tumor sites. Furthermore, treating cells with UiO-DOX@FA/TPP nanosystem led to extensive gene expression changes, primarily enriched in Ca2+ signaling and autophagy regulation. The stepwise targeted luminescent UiO-DOX@FA/TPP nanosystem allow for the precise identification and delineation of ovarian cancer boundaries, monitoring of drug transport in real-time, and targeted delivery to mitochondria for inducing apoptosis. This innovative approach provides a theoretical and methodological basis for integrating ovarian cancer diagnosis and treatment.

Facile Synthesis of a Multifunctional Porous Organic Polymer Nanosonosensitizer (mHM@HMME) for Enhanced Cancer Sonodynamic Therapy.

Sonodynamic therapy (SDT), which involves the activation of sonosensitizers to generate cytotoxic reactive oxygen species under ultrasound irradiation, is a promising noninvasive modality for cancer treatment. However, the clinical translational application of SDT is impeded by the lack of efficient sonosensitizers, the inefficient accumulation of sonosensitizers at tumor sites, and the complicated immunosuppressive tumor microenvironment. Herein, we developed a facilely synthesized multifunctional porous organic polymer nanosonosensitizer (mHM@HMME) for enhanced SDT. Specifically, mHM@HMME nanosonosensitizers were prepared by incorporating chemotherapeutic mitoxantrone into the one-step synthesis process of disulfide bond containing porous organic polymers, followed by loading with organic sonosensitizer (HMME) and camouflaging with a cancer cell membrane. Due to the cancer cell membrane camouflage, this multifunctional mHM@HMME nanosonosensitizer showed prolonged blood circulation and tumor targeting aggregation. Under ultrasound irradiation, the mHM@HMME nanosonosensitizer exhibited a satisfactory SDT performance both in vitro and in vivo. Moreover, the potent SDT combined with glutathione-responsive drug release in tumor cells induced robust immunogenic cell death to enhance the antitumor effect of SDT in turn. Overall, this facilely synthesized multifunctional mHM@HMME nanosonosensitizer shows great potential application in enhanced SDT.

Personalized Nanovaccines Enhance Lymph Node Accumulation and Reprogram the Tumor Microenvironment for Improved Photodynamic Immunotherapy.

Tumor immunotherapy has emerged as an efficacious therapeutic approach that mobilizes the patient's immune system to achieve durable tumor suppression. Here, we design a photodynamic therapy-motivated nanovaccine (Dex-HDL/ALA-Fe3O4) co-delivering 5-aminolevulinic acid and Fe3O4 nanozyme that demonstrate a long-term durable immunotherapy strategy. After vaccination, the nanovaccine exhibits obvious tumor site accumulation, lymph node homing, and specific and memory antitumor immunity evocation. Upon laser irradiation, Dex-HDL/ALA-Fe3O4 effectively generates reactive oxygen species at the tumor site not only to induce the immunogenic cell death-cascade but also to trigger the on-demand release of full types of tumor antigens. Intriguingly, Fe3O4 nanozyme-catalyzed hydrogen peroxide generated oxygen for alleviating tumor hypoxia and modifying the inhibitory tumor microenvironment, thereby exhibiting remarkable potential as a sensitizer. The intravenous administration of nanovaccines in diverse preclinical cancer models has demonstrated remarkable tumor regression and inhibition of postoperative tumor recurrence and metastasis, thereby enabling personalized treatment strategies against highly heterogeneous tumors.

Tumor microenvironment activated and amplified self-luminescent nano photosensitizers for efficient treatment of triple negative breast cancer

Triple negative cancer (TNBC) is characterized as an aggressive phenotype lacking a specific therapeutic target. To date, self-illuminating photodynamic therapy (PDT) based on chemiluminescence resonance energy transfer (CRET) has emerged as a potential alternative for TNBC treatment by generating singlet oxygen (1O2), overcoming limitations in light penetration. However, this self-illuminating strategy heavily relies on endogenous hydrogen peroxide (H2O2) and oxygen (O2) within the tumor microenvironment (TME), resulting in inefficient therapeutic performance. In this study, we designed CLT@DPD nanoparticles capable of self-illumination via CRET and TME regulation through self-supplying H2O2 and O2. This nanoparticle was constructed by encapsulating luminol-tetreaphenylporphyrin conjugate (LT) and nanoscale CaO2 with DSPE-PEG 2000 and dioleoylphosphatidylcholine (DOPC). A good accumulation at tumor site was achieved due to enhanced permeability and retention (EPR) effect after intravenous injection of CLT@DP. Responsive to the high H2O2 levels and acidic aqueous conditions of TME, LT can be oxidized to produce 1O2via CRET, and the CaO2 can be decomposed to supply H2O2 and O2. Additionally, the presence of DOPC helps to enhance the permeability of the micelle shell under the oxidation of 1O2, thereby accelerating the release of H2O2 and O2. Our proposed nanoparticles exhibit excellent performance in eradicating in situ tumor cells and inhibiting metastasis by simultaneously enhancing self-luminous PDT and alleviating oxygen depletion in TME.

Manganese oxide-constructed multifunctional biomimetic nanovaccine for robust tumor-specific T cell priming and chemodynamic therapy

The development of manganese oxide-based chemodynamic immunotherapy is emerging as a key strategy against solid tumors. However, the limited efficacy of nanoplatform in inducing efficient tumor therapeutic effects and creating the prominent antitumor immune responses remains a crucial issue. In this study, we construct a novel multifunctional biomimetic nanovaccine comprising manganese oxide-loaded poly(2-diisopropylaminoethyl methacrylate) (MP) nanoparticles and a coating layer of hybrid cell membrane (RHM) derived from manganese oxide-remodeled 4T1 cells and dendritic cells (DCs) (collectively called MP@RHM) for combination chemodynamic immunotherapy. Compared with the nanovaccines coated with the single cell membrane, the MP@RHM nanovaccine highly efficiently activates both DCs and T cells to boost tumor-specific T cell, owing to the synergistic effects of abundant damage-associated molecular patterns, Mn2+, and T cell-stimulating moieties. Upon peritumoral injection, the MP@RHM nanovaccine targets both the tumor site for focused chemodynamic therapy and the lymph nodes for robust tumor-specific T cell priming, thereby achieving highly efficient chemodynamic immunotherapy. Moreover, as a preventive cancer nanovaccine, MP@RHM generates strong immunological memory to inhibit postoperative tumor metastasis and recurrence. Our study findings highlight a promising approach to construct a multifunctional biomimetic nanovaccine for personalized chemodynamic immunotherapy against solid tumors.

Matrix Metalloproteinase- and pH-Sensitive Nanoparticle System Enhances Drug Retention and Penetration in Glioblastoma.

Glioblastoma (GBM) is a primary malignant brain tumor with limited therapeutic options. One promising approach is local drug delivery, but the efficacy is hindered by limited diffusion and retention. To address this, we synthesized and developed a dual-sensitive nanoparticle (Dual-NP) system, formed between a dendrimer and dextran NPs, bound by a dual-sensitive [matrix metalloproteinase (MMP) and pH] linker designed to disassemble rapidly in the tumor microenvironment. The disassembly prompts the in situ formation of nanogels via a Schiff base reaction, prolonging Dual-NP retention and releasing small doxorubicin (Dox)-conjugated dendrimer NPs over time. The Dual-NPs were able to penetrate deep into 3D spheroid models and detected at the tumor site up to 6 days after a single intratumoral injection in an orthotopic mouse model of GBM. The prolonged presence of Dual-NPs in the tumor tissue resulted in a significant delay in tumor growth and an overall increase in survival compared to untreated or Dox-conjugated dendrimer NPs alone. This Dual-NP system has the potential to deliver a range of therapeutics for efficiently treating GBM and other solid tumors.

68Ga]Ga-FAPI-46 PET/CT for penile cancer - a feasibility study.

Penile cancer is a rare entity and has a good prognosis in localized stage. Delayed surgical treatment of lymphatic disease is associated with poor overall survival but conventional imaging cannot detect occult lymph node metastasis sufficiently. Imaging cancer related fibroblasts has shown promising results as non-invasive staging tool in various tumor entities but has not yet been evaluated in penile cancer. In this single-center pilot study, patients planned for surgical treatment for penile cancer underwent preoperatively [68Ga]Ga-FAPI-46 PET/CT. Post-operative histopathology was compared to [68Ga]Ga-FAPI-46 PET/CT results. From January 2022 to June 2022, a total number 11 patients with histopathologically proven penile cancer underwent surgery and received [68Ga]Ga-FAPI-46 PET/CT prior therapy. 8 primary tumor sites and 4 lymph node regions were analyzed. FAPI uptake was increased on primary tumor site (SUVmax 16.2 (9.1 - 25.8)). Histopathological proven lymph node regions showed highly increased FAPI uptakes (SUVmax 17.9 (16.4 - 23.5) on [68Ga]Ga-FAPI-46 PET/CT. In this first pilot cohort, there were no false-positive FAPI uptake which might allow the detection of occult lymph node metastasis by [68Ga]Ga-FAPI-46 PET/CT and might consequently lead to omitting lymph node regions during surgery that had no increased FAPI uptake pre-operatively.