Platform For Therapy Research Articles

UiO-66 MOFs-Based "Epi-Nano-Sonosensitizer" for Ultrasound-Driven Cascade Immunotherapy against B-Cell Lymphoma.

B-cell lymphoma (BCL) is a hematological malignancy with high heterogeneity and represents an aggressive proliferation of mature B-cells. Despite the initial success of traditional treatments for BCL in clinical trials, a majority of patients eventually develop resistance to therapy and have poor clinical outcomes. Epigenetic dysregulation is a major contributor to the pathogenesis of BCL, and therapies targeting epigenetic pathways is a promising alternative strategy for treating BCL. Herein, we developed a metal-organic framework (MOF)-based nano-sonosensitizer for ultrasound-driven cascade immunotherapy against BCL. The nano-sonosensitizer was synthesized by encapsulating copper complex of the m6A-mRNA demethylase inhibitor into UiO-66-NH2, which possesses a Z-scheme heterostructure and allows efficient electron-hole pair separation for generating reactive oxygen species (ROS) under ultrasound activation. These CuR@UiO66 sonosensitizers were functionalized with mPEG-PO3 and anti-CD19 antibody, and the resulting CRUPPA19 particles could specifically accumulate in the BCL tissue and also target lymphoma cells that infiltrated into the bone marrow. Once internalized, CRUPPA19 could induce intracellular ROS production and apoptosis under ultrasound irradiation. Subsequently, ultrasonic stimulation triggered autophagy-mediated release of Cu and Rhein from CRUPPA19, thereby increasing protein lipoylation and global mRNA methylation, which led to cuproptosis and the transcriptional repression PDL1, respectively. These cascades synergistically induced immunogenic cell death in the tumors and promoted activation of CD8+ T cells, eventually leading to an antilymphoma immune response. CRUPPA19-mediated sono-immunotherapy not only eliminated the primary and metastatic lymphomas but also cleared lymphoma cells from the bone marrow. This study provided an insight into a MOF-based nanoepigenetic therapy platform with ultrasound-triggered cascade amplification for enhanced antihematological tumor immunity.

Research trends in the use of nanobodies for cancer therapy.

Although there are many challenges in using nanobodies for treating various complex tumor diseases, including rapid renal clearance and the complex blood-brain barrier environment, nanobodies have shown great potential due to their high antigen affinity, excellent tumor penetration ability, and favorable safety profile. Since the discovery of the variable domain (VHH) of camelid heavy-chain antibodies in 1993, nanobodies have been progressively applied to various cancer therapy platforms, such as antagonistic drugs and targeting agents for effector domains. In recent years, several nanobody-based drugs, including Caplacizumab, KN-035, and Ozoralizumab, have been approved for clinical use. Among them, KN-035 is used for treating advanced solid tumors, and these advancements have propelled nanobody development to new heights. Currently, nanobodies are being rapidly applied to the treatment of a wide range of diseases, from viral infections to cancer, demonstrating strong advantages in areas such as targeted protein degradation, bioimaging, nanobody-drug conjugation, bispecific T-cell engagers, and vaccine applications. Bibliometric tools, including CiteSpace, HisCite Pro, and Alluvial Generator, were employed to trace the historical development of nanobodies in cancer research. The contributions of authors, countries, and institutions in this field were analyzed, and research hotspots and emerging trends were identified through keyword analysis and influential articles. Future trends were also predicted. This study provides a unique, comprehensive, and objective perspective on the use of nanobodies in tumor research, laying a foundation for future research directions and offering valuable insights for researchers in the field.

In Case You Haven't Heard…

The online therapy industry has grown significantly in recent years, driven by the increasing demand for accessible mental health care. BetterHelp, the world's largest online therapy platform, has surpassed 5 million people across over 100 countries worldwide who have trusted its therapy services on their mental health journey, according to a Jan. 22 news release. Courtesy of BetterHelp's network of 35,000 licensed and vetted therapists, 72% of BetterHelp clients experienced a reduction in symptoms in their first 12 weeks of therapy on the platform. “As this milestone and report both demonstrate, BetterHelp is doing something that has never been done before: providing access to high‐quality mental health care at a massive scale,” said Fernando Madeira, president and CEO of BetterHelp. “Over 5 million people have trusted us with their mental health journeys at sensitive moments in their lives, and we're proud to be able to provide this transparency about our platform and clinical outcomes in return.” In 2024, BetterHelp eradicated barriers to wellness across the globe, with 40% of new members experiencing the benefits of therapy for the first time ever, and met over 93% of client preferences when matching with a therapist, the release stated.

A Dual Energy CT-Guided Intelligent Radiation Therapy Platform.

The integration of advanced imaging and artificial intelligence (AI) technologies in radiotherapy has revolutionized cancer treatment by enhancing precision and adaptability. This study introduces a novel Dual Energy CT (DECT)-Guided Intelligent Radiation Therapy (DEIT) platform designed to streamline and optimize the radiotherapy process. The DEIT system combines DECT, a newly designed dual-layer multi-leaf collimator, deep learning algorithms for auto-segmentation, automated planning and QA capabilities. The DEIT system integrates an 80-slice CT scanner with an 87 cm bore size, a linear accelerator delivering four photon and five electron energies, and a flat panel imager optimized for MV Cone Beam CT acquisition. A comprehensive evaluation of the system's accuracy was conducted using end-to-end tests. Virtual monoenergetic CT images and electron density images of the DECT were generated and compared on both phantom and patient. The system's auto-segmentation algorithms were tested on five cases for each of the 99 organs at risk, and the automated optimization and planning capabilities were evaluated on clinical cases. The DEIT system demonstrated systematic errors of less than 1 mm for target localization. DECT reconstruction showed electron density mapping deviations ranging from -0.052 to 0.001, with stable HU consistency across monoenergetic levels above 60 keV, except for high-Z materials at lower energies. Auto-segmentation achieved dice similarity coefficients above 0.9 for most organs with inference time less than 2 seconds. Dose-volume histogram (DVH) comparisons showed improved dose conformity indices and reduced doses to critical structures in Auto-plans compared to Manual Plans across various clinical cases. Additionally, high gamma passing rates at 2%/2mm in both 2D (above 97%) and 3D (above 99%) in vivo analyses further validate the accuracy and reliability of treatment plans. The DEIT platform represents a viable solution for radiation treatment. The DEIT system utilizes AI-driven automation, real-time adjustments, and CT imaging to enhance the radiotherapy process, improving both efficiency and flexibility.

A tumor microenvironment-responsive multifunctional MoS2-Ru nanocatalyst with photothermally enhanced chemodynamic activity.

Targeting the unique characteristics of the tumor microenvironment (TME) has emerged as a highly promising strategy for cancer therapy. Chemodynamic therapy (CDT), which leverages the TME's intrinsic properties to convert H2O2 into cytotoxic hydroxyl radicals (˙OH), has attracted significant attention. However, the effectiveness of CDT is often limited by the catalytic efficiency of the materials used. Although Molybdenum disulfide (MoS2) exhibits remarkable chemodynamic and photothermal properties, its limited efficiency in catalyzing the conversion of endogenous H2O2 into ˙OH radicals remains a significant challenge. To overcome this, we developed a nanocomposite of MoS2 and ruthenium (MoS2-Ru), by incorporating Ru into MoS2 nanosheets. The MoS2-Ru nanocomposite demonstrated significantly enhanced catalytic activity at a low concentration (500 ng mL-1), whereas the same effect was achieved only with 20 μg mL-1 of MoS2. The low Michaelis-Menten constant (Km) of 4.69 mM further confirmed the superior catalytic activity of the nanocomposite, indicative of the enhanced enzyme-like activity. Additionally, the integration of Ru in MoS2 reduced the bandgap to 1.18 eV, facilitating near-infrared (NIR) absorption with a high conversion efficiency of 41%. Electron paramagnetic resonance (EPR) analysis confirmed robust ˙OH radical generation driven by the combined chemodynamic and photothermal effects. In vitro studies using triple-negative breast cancer (TNBC) cells validated the synergistic activity of CDT and PTT, demonstrating significant ˙OH radical production under TME conditions, leading to effective cancer cell death. This study underscores the potential of MoS2-Ru nanocomposites as a versatile and powerful platform for multimodal cancer therapy, seamlessly integrating CDT and PTT to achieve synergistic, precise, and highly effective treatment outcomes.

Enhancing DNA Vaccine Delivery Through Stearyl-Modified Cell-Penetrating Peptides: Improved Antigen Expression and Immune Response In Vitro and In Vivo.

Inefficient cellular uptake is a significant limitation to the efficacy of DNA vaccines. In this study, we introduce S-Cr9T, a stearyl-modified cell-penetrating peptide (CPP) designed to enhance DNA vaccine delivery by forming stable complexes with plasmid DNA, thereby protecting it from degradation and promoting efficient intracellular uptake. In vitro studies showed that S-Cr9T significantly improved plasmid stability and transfection efficiency, with optimal performance at an N/P ratio of 0.25. High-content imaging revealed that the S-Cr9T-plasmid complex stably adhered to the cell membrane, leading to enhanced plasmid uptake and transfection. In vivo, S-Cr9T significantly increased antigen expression and triggered a robust immune response, including a threefold increase in IFN-γ secretion and several hundred-fold increases in antibody levels compared to control groups. These findings underscore the potential of S-Cr9T to enhance DNA vaccine efficacy, offering a promising platform for advanced gene therapy and vaccination strategies.

Advances in soft nanoparticle-based platforms for human and veterinary trichomoniasis therapy: A scoping review.

This scoping review focuses on drug delivery systems based on soft materials designed for the administration of drugs with anti-Trichomonas vaginalis activity. It primarily examines their use in addressing human trichomoniasis, exploring their physicochemical characteristics, in vitro and in vivo evaluation and identifying existing challenges and gaps. Given the economic burden and the One Health approach, formulations developed aiming at treating animal infections - cattle and poultry - were also discussed. The review involved searching electronic databases, such as PubMed, Scopus, and Web of Science, to find studies published until May 2024; out of the 103 articles retrieved, 18 fulfilled the eligibility criteria. This study investigated soft-nanoparticle formulations, including polymericand lipid-based systems, and their incorporation into suitable formulations for topical application, including hydrogels and polymeric films. Additionally, the discussion covered toxicology and highlighted the knowledge gaps related to the potential use of these formulations in humans. Anti-trichomonas soft nano-based formulations emerge as promising candidates for treating gynecological and animal infections. In conclusion, further preclinical testing is necessary, as none of the formulations have progressed to human clinical trials and have only been evaluated in animal models.

Fluorescent Heterocyclic Compound-Loaded Bi2Se3-Polysorbate Nanoparticles for Targeted Therapy in Non-Small Cell Lung Cancer.

This study introduces a novel approach for non-small cell lung cancer (NSCLC) treatment by developing Bi2Se3-Polysorbate nanoparticles as a multifunctional platform for photothermal therapy and targeted drug delivery. The Bi2Se3-Polysorbates nanoparticles are engineered as innovative photosensitive drug carriers, enhancing biocompatibility through the combination of Bi2Se3 and Polysorbates. Characterization techniques such as Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and ultraviolet-visible (UV-Vis) spectroscopy confirm the successful synthesis of the nanoparticles. In a breakthrough step, these nanoparticles are combined with a novel heterocyclic drug (drug-1), verified by single-crystal analysis, to create the Bi2Se3-Polysorbates@drug-1 composite. Biological evaluations show that the system significantly inhibits cell proliferation in NSCLC cells, and molecular docking studies reveal that drug-1 interacts with the target protein through hydrogen bonds, halogen bonds, and hydrophobic interactions, suggesting promising anti-cancer activity. This research presents a novel multifunctional nanoplatform for effective drug delivery and offers a new strategy for the treatment of NSCLC, demonstrating significant advancements in cancer therapy.

AAVR Expression is Essential for AAV Vector Transduction in Sensory Hair Cells.

Adeno-associated virus (AAV) vectors are a leading platform for gene therapy. Recently, AAV-mediated gene therapy in the inner ear has progressed from laboratory use to clinical trials, but the lower transduction rates in outer hair cells (OHCs) in the organ of Corti and in vestibular hair cells in adult mice still pose a challenge. OHCs are particularly vulnerable to inner ear insults. In this study, we demonstratedthat expression of a key AAV receptor (AAVR, Kiaa0319l, or Au040320) in OHCs and vestibular hair cells decreases significantly in mature mice and AAV particles directly interact with AAVR by forming complexes. Consequently, antibody blockage of AAVR significantly inhibits AAV transduction in sensory hair cells in cochlear explants. Moreover, use of AAVR knockout mice confirms inhibition of AAV transduction in sensory hair cells in vivo. Finally, conditional overexpression of AAVR in sensory hair cells of adult mice successfully restores AAV transduction efficiency in OHCs and vestibular hair cells. In conclusion, this strong evidence that AAVR is essential for AAV transduction in sensory hair cells will help to increase the efficacy of future gene therapy in inner ear.

Synergistic Antibacterial Action of Norfloxacin-Encapsulated G4 Hydrogels: The Role of Boronic Acid and Cyclodextrin.

In this present study, we developed and characterized a series of supramolecular G4 hydrogels by integrating β-cyclodextrin (β-CD) and boronic acid linkers into a supramolecular matrix to enhance antibacterial activity against Staphylococcus aureus (S. aureus). We systematically investigated how varying the number of free boronic acid moieties (ranging from two to six), along with guanosine and β-CD content, influences both the structural integrity and antimicrobial efficacy of these materials. Comprehensive characterization using FTIR, circular dichroism, X-ray diffraction, SEM, AFM, and rheological measurements confirmed successful synthesis and revealed that higher boronic acid content correlated with a stronger, more organized network. The most effective hydrogel displayed an inhibition zone of 25 mm in disk diffusion assays, and was further explored as a drug delivery platform, with the aim to exploit the capacity of the free β-CD cavity of the hydrogels to incorporate hydrophobic drugs. Norfloxacin (Nfx), a poorly water-soluble antibiotic, was successfully encapsulated within the hydrogel matrix through the inclusion of complex formation with β-CD, improving its solubility and enabling sustained, targeted release. The Nfx-loaded hydrogel expanded the inhibition zone to 49 mm and completely eradicated S. aureus cells within 24 h, outperforming both the unloaded hydrogel and free Nfx. These results highlight the synergistic effect of boronic acid moieties and controlled drug release, underlining the potential of these hydrogels as versatile platforms for localized antimicrobial therapy, such as in wound dressings or implant coatings. Nevertheless, further in vivo studies and long-term stability assessments are needed to fully establish clinical relevance, safety, and scalability before these systems can be translated into routine healthcare applications.

A Multifunctional MIL-101-NH2(Fe) Nanoplatform for Synergistic Melanoma Therapy.

Melanoma is an aggressive form of skin cancer, and single-modality treatments often fail to prevent tumor recurrence and metastasis. Combination therapy has emerged as an effective approach to improve treatment outcomes. In this study, we developed a multifunctional nanoplatform, MIL@DOX@ICG, utilizing MIL-101-NH2(Fe) as a carrier to co-deliver the chemotherapeutic agent doxorubicin (DOX) and the photosensitizer indocyanine green (ICG). MIL-101-NH2(Fe) was synthesized via a hydrothermal method. Drug release was evaluated under different pH conditions, and the photothermal effect was tested under near-infrared (NIR) laser irradiation. Hydroxyl radical and reactive oxygen species generation capacities were quantified. Cellular studies using B16F10 cells assessed cytotoxicity, cellular uptake, migration inhibition, and colony formation suppression. In vivo experiments in melanoma-bearing mice evaluated antitumor efficacy and systemic safety through tumor growth inhibition, histological analyses, and toxicity assessments. MIL@DOX@ICG exhibited a uniform octahedral structure with a particle size of approximately 139 nm and high drug loading efficiencies for DOX (33.70%) and ICG (30.59%). The nanoplatform demonstrated pH-responsive drug release and potent photothermal effects. The generation of hydroxyl radicals via the Fenton reaction and reactive oxygen species production under NIR laser irradiation by MIL@DOX@ICG were confirmed. In vitro assessments revealed significant cytotoxicity of MIL@DOX@ICG against B16F10 cells under NIR laser irradiation, with improved efficacy in inhibiting cell proliferation and migration. In vivo studies confirmed the superior antitumor efficacy of MIL@DOX@ICG + NIR treatment, synergistically harnessing chemotherapy, photothermal therapy, photodynamic therapy, and chemodynamic therapy effects while maintaining excellent biocompatibility. Our findings underscore the potential of MIL-101-NH2(Fe) nanoparticles as a versatile and effective platform for synergistic melanoma therapy, offering a promising strategy for overcoming the limitations of conventional treatment modalities.

Chitosan nanoparticles loaded with metformin and digoxin synergistically inhibit MCF-7 breast cancer cells through suppression of NOTCH-1 and HIF-1α gene expression

This study investigated the potential anticancer efficacy of co-treating the MCF-7 breast cancer cell line with chitosan nanoparticles (Cs NPs) loaded with metformin (Met) and digoxin (Dig). The Cs NPs had a size range of 90.6–148.7 nm and a zeta potential of +11.7 to +11.9 mV, indicating a positive surface charge. Notably, the Cs NPs demonstrated high encapsulation efficiencies, with values of 90.97 ± 5.14 % for Met and 92.12 ± 3.81 % for Dig, indicating effective loading of both drugs. The results revealed that the co-delivery of Met and Dig via Cs NPs significantly enhanced the anticancer efficacy, outperforming the treatment with individual free drugs or their combination, thereby demonstrating the potential benefits of nanoparticle-mediated co-administration. The drugs-loaded Cs NPs induced a marked increase in apoptosis in MCF-7 cells, with a cell death rate of 67.56 %, and significantly reduced mammosphere size by 48.08 %, thereby demonstrating a superior therapeutic efficacy compared to treatment with individual free drugs or their combination. Notably, the drug-loaded Cs NPs exhibited potent anti-migratory and anti-angiogenic effects, significantly inhibiting cell migration and new blood vessel formation, which may contribute to overcoming the inherent resistance of tumors to conventional therapies. Mechanistically, the co-treatment with drugs-loaded Cs NPs was found to downregulate the expression of NOTCH-1 and HIF-1α, two key transcription factors involved in tumor cell survival and adaptation, suggesting that their inhibition is a crucial component of the therapeutic efficacy of this treatment strategy. Collectively, the findings of this study suggest that the co-delivery of Met and Dig via chitosan Cs NPs represents a promising therapeutic strategy for breast cancer, as it effectively targets key pathways involved in tumor growth and progression, and underscores the potential of Cs NPs as a versatile platform for cancer therapy.

Construction of a Tungsten Trioxide Modified Smart-Polymers as a NIR-Responsive Platform for Photo-Thermal Therapy on Hepatocellular Cancer

Cancer remains a predominant contributor to both mortality and morbidity on a global scale, with over 10 million new cases diagnosed annually. The aim of this work was to prepare and evaluate erlotinib hydrochloride loaded tungsten trioxide modified with smart polymers for their anticancer potential. The morphology, crystallinity, chemical bonding, and thermal behavior of the nanoadsorbent were characterized using field emission scanning electron microscopy, transmission electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, and thermogravimetric analyses. The optimization of the drug on the synthesized adsorbent was investigated utilizing response surface methodology-central composite design. The maximum sorption efficiency of 90.18% was achieved at the initial drug concentration of 32.82 mg L-1, a pH of 8.17, a temperature of 32.93 °C, and a contact time of 16.08 min. The drug sorption process follows the Langmuir isotherm and it displays pseudo-first-order kinetics. The nanocarrier showed a significant release profile for 6 h with a maximum release percentage of 99.81% in simulated cancer fluid at high temperatures. The nanocarrier showed low drug release without near-infrared laser irradiation and a rapid release rate over 15 min of near-infrared laser irradiation. The drug release properties fit the Korsmeyer-Peppas model, with a diffusion exponent indicative of both diffusion and erosion release mechanisms. In-vitro cytotoxicity of the nanocarrier in normal cells indicated that it had no significant cytotoxicity. The cytotoxicity of the nanocarrier in Hep-G2 hepatocellular carcinoma cell lines was evaluated by MTT assay, and the data showed that the nanocarrier has excellent cytotoxic activity (75.45%).

A PDI-based NIR-II fluorescence imaging guided molecular phototheranostic platform for GSH-triggered gas therapy, mild photothermal therapy and NIR-activated photodynamic therapy

A PDI-based NIR-II fluorescence imaging guided molecular phototheranostic platform for GSH-triggered gas therapy, mild photothermal therapy and NIR-activated photodynamic therapy

Intratumoral delivery of Mitomycin C using bio-responsive Gellan Gum Nanogel: In-vitro evaluation and enhanced chemotherapeutic efficacy.

Intratumoral drug delivery systems hold immense promise in overcoming the limitations of conventional IV chemotherapy, particularly in enhancing therapeutic efficacy and minimizing systemic side effects. In this study, we introduce a novel redox-responsive intratumoral nanogel system that combines the biocompatibility of natural polysaccharides with the tailored properties of synthetic polymers. The nanogel features a unique cross-linked architecture incorporating redox-sensitive segments, designed to leverage the elevated glutathione levels in the tumor microenvironment for controlled drug release. Synthesis was performed using a microwave-assisted free radical polymerization technique, which facilitated efficient and rapid cross-linking. A Quality by Design strategy was implemented to optimize key parameters, ensuring the nanogel's suitability for intratumoral delivery, including ideal injectability, viscosity, and drug release characteristics. Mitomycin C (MMC), a chemotherapeutic agent effective against hypoxic tumor cells, was efficiently loaded within the cross-linked nanogel. Optimal stability and drug loading were achieved at a 2:1 nanogel/MMC ratio. The nanogel's structure and composition were confirmed using elemental analysis, FTIR, NMR spectroscopy, and XRD. Stability studies demonstrated its robustness in simulated physiological conditions. In vitro evaluations revealed enhanced cellular uptake of the MMC-loaded nanogel, leading to effective cell cycle arrest, mitochondrial membrane potential disruption, and apoptosis, Co-localization studies with Lysotracker Green, a lysosomal marker, revealed that the nanogels were trafficked to lysosomes. Pharmacokinetic analysis showed significantly reduced systemic exposure (lower plasma Cmax) compared to intravenous administration, while biodistribution studies using IVIS imaging demonstrated prolonged retention of the nanogel within tumor tissues. In vivo studies using a 4T1 xenograft mouse model highlighted the superior antitumor efficacy of the intratumoral nanogel system compared to free MMC. The nanogel treatment resulted in significant tumor volume reduction, minimal changes in body weight, and reduced lung metastasis, as confirmed by histological analysis (HE staining). Ki67 and TUNEL assays of tumor tissues further substantiated the nanogel's ability to suppress proliferation and induce apoptosis. These outcomes directly correlate with our goal of using a redox responsive nanogel system to improve localized drug delivery and minimize systemic side effects. This biodegradable, redox-responsive polymer system represents a significant advance in nanomedicine, offering a promising platform for safe and effective localized cancer therapy.

Exploring the potential of plasma and adipose mesenchymal stem cell-derived extracellular vesicles as novel platforms for neuroinflammation therapy

Persistent reactive oxygen species (ROS) and neuroinflammation contribute to the onset and progression of neurodegenerative diseases, underscoring the need for targeted therapeutic strategies to mitigate these effects. Extracellular vesicles (EVs) show promise in drug delivery due to their biocompatibility, ability to cross biological barriers, and and specific interactions with cell and tissue receptors. In this study, we demonstrated that human plasma-derived EVs (pEVs) exhibit higher brain-targeting specificity, while adipose-derived mesenchymal stem cells EVs (ADMSC-EVs) offer regenerative and immunomodulatory properties. We further investigated the potential of these EVs as therapeutic carriers for brain-targeted drug delivery, using Donepezil (DNZ) as the model drug. DNZ, a cholinesterase inhibitor commonly used for Alzheimer's disease (AD), also has neuroprotective and anti-inflammatory properties. The size of EVs used ranged from 50 to 300 nm with a surface charge below −30 mV. Both formulations showed rapid cellular internalization, without toxicity, and the ability to cross the blood-brain barrier (BBB) in a zebrafish model. The have analyzed the anti-inflammatory and antioxidant actions of pEVs-DNZ and ADMSC-EVs-DNZ in the presence of lipopolysaccharide (LPS). ADMSC-EVs significantly reduced the inflammatory mediators released by HMC3 microglial cells while treatment with pEVs-DNZ and ADMSC-EVs-DNZ lowered both phagocytic activity and ROS levels in these cells. In vivo experiments using zebrafish larvae revealed that both EV formulations reduced microglial proliferation and exhibited antioxidant effects. Overall, this study highlights the potential of EVs loaded with DNZ as a novel approach for treating neuroinflammation underlying various neurodegenerative diseases.

Abstracts of the APTA Academy of Pediatric Physical Therapy Platform Presentations at the Combined Sections Meeting.

Abstracts of the APTA Academy of Pediatric Physical Therapy Platform Presentations at the Combined Sections Meeting.

Engineered Cellular Therapies for the Treatment of Thoracic Cancers.

Thoracic malignancies (lung cancers and malignant pleural mesothelioma) are prevalent worldwide and are associated with high morbidity and mortality. Effective treatments are needed for patients with advanced disease. Cell therapies are a promising approach to the treatment of advanced cancers that make use of immune effector cells that have the ability to mediate antitumor immune responses. In this review, we discuss the prospect of chimeric antigen receptor-T (CAR-T) cells, natural killer (NK) cells, T cell receptor-engineered (TCR-T) cells, and tumor-infiltrating lymphocytes (TILs) as treatments for thoracic malignancies. CAR-T cells and TILs have proven successful in several hematologic cancers and advanced melanoma, respectively, but outside of melanoma, results have thus far been unsuccessful in most other solid tumors. NK cells and TCR-T cells are additional cell therapy platforms with their own unique advantages and challenges. Obstacles that must be overcome to develop effective cell therapy for these malignancies include selecting an appropriate target antigen, combating immunosuppressive cells and signaling molecules present in the tumor microenvironment, persistence, and delivering a sufficient quantity of antitumor immune cells to the tumor. Induced pluripotent stem cells (iPSCs) offer great promise as a source for both NK and T cell-based therapies due to their unlimited expansion potential. Here, we review clinical trial data, as well as recent basic scientific advances that offer insight into how we may overcome these obstacles, and provide an overview of ongoing trials testing novel strategies to overcome these obstacles.

Interlaboratory Measurement of Adeno-Associated Virus: Comparative Quantification of Full and Empty Capsids.

Recombinant adeno-associated virus (AAV) is one of the main viral vector-based gene therapy platforms. AAV is a virus consisting of a ≈25 nm diameter capsid with a ≈4.7 kb cargo capacity. Therapeutic safety and efficacy depend on the correct encapsidation of the DNA in individual virus particles, which is often characterized by the single scalar value of the ratio of full capsids with complete viral genomes to the total viral capsid number [the full-to-total (FTT) ratio]. This study reports on the interlaboratory and intertechnique variations of measurement methods for FTT among a cohort of organizations. The analytical methods used were sedimentation velocity analytical ultracentrifugation (SV-AUC) with UV/Vis and/or Rayleigh interference optics, size exclusion chromatography (SEC) with multi-angle light scattering (MALS), and tandem UV/Vis and/or refractive index, cryogenic electron microscopy, dual-wavelength ultraviolet spectrophotometry, and ELISA coupled with quantitative PCR (qPCR, dPCR, or ddPCR). FTT measurements for both AAV5 and AAV8 serotypes were similar, except for PCR-ELISA. The optical techniques (UV spectroscopy/SEC-MALS) showed <10% SD between laboratories, likely from the uniformity of existing industry protocols. AUC, while demonstrating good repeatability, had ≈25% SD interlaboratory, suggesting the need for standardized methods. PCR and ELISA had poor reproducibility due to variations in both PCR and ELISA protocols and instrumentation. The discussion presents intended future efforts to improve and harmonize these measurements to increase both the repeatability and reproducibility of AAV viral particle critical quality attributes such as FTT.

Nanoscale Liposomes Co-Loaded with Irinotecan Hydrochloride and Thalidomide for Colorectal Cancer Synergistic Therapy.

Irinotecan hydrochloride (CPT-11) is one of the first-line drugs used in the clinical treatment of colorectal cancer (CRC). However, the concomitant adverse effect of delayed diarrhea has hindered its clinical use. CPT-11 combined with Thalidomide (THA) therapy is considered a palliative strategy. To optimize the synergistic treatment of CPT-11 and THA, co-loaded liposomes are constructed using cholesterol, lecithin, and 1, 2-Distearoyl-sn-glycero-3-phosphoethanolamine-Poly(ethylene glycol) (DSPE-PEG) as the "immune and gut microbiota regulator." The co-loaded liposomes, which possess good stability, are prepared by the solvent injection method. After the treatment with the co-loaded liposomes, tumor growth in CRC-bearing mice is significantly inhibited. In particular, the co-loaded liposomes demonstrate favorable diarrhea-relieving effects through the modulation of inflammatory cytokines and gut microbiota. These findings suggest that the co-loaded liposomes have great potential as a combined drug-delivery platform for CRC therapy.