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Material-driven therapeutics: Functional nanomaterial design paradigms revolutionizing osteosarcoma treatment
Zhang Z, He F, Li W, Liu B, Deng C, Qin X (2025) Material-driven therapeutics: Functional nanomaterial design paradigms revolutionizing osteosarcoma treatment. J Funct Biomater 16(6):213. doi: 10.3390/jfb16060213 PMID: 40558899
Objective: To examine nanomaterial applications in Osteosarcoma (OS) therapy through a materials science lens, analyzing mechanism specific interventions. The analysis establishes a framework for developing next-generation nanotherapeutic platforms to address persistent limitations in OS management.
Summary: Phytic acid (PA)-functionalized nanoparticles (e.g., MnO2-PA) exploit high hydroxyapatite affinity for osseous tumor accumulation. Bone-specific targeting is exemplified by saporin-boronated nanotherapeutics, which achieve ribosomal inactivation through hydroxyapatite binding, offering a targeted approach for bone malignancies.
Usage: Saporin delivery in an orthotopic model significantly inhibited Osteosarcoma. GPSP (100 μg/kg saporin + 133.3 μg/kg GP + 140 μg/kg PASP) was intravenously injected with a Saporin concentration of 100 µg/kg. In a Bone-Metastatic Breast Cancer disease model, GPSP (150 μg/kg saporin + 200 μg/kg GP + 210 μg/kg PASP) was injected with a Saporin concentration of 150 µg/kg.
Related Products: Saporin (Cat. #PR-01)
Microgliosis in the spinal dorsal horn early after peripheral nerve injury is associated with damage to primary afferent aβ-fibers
Shibata Y, Matsumoto Y, Kohno K, Nakashima Y, Tsuda M (2025) Microgliosis in the spinal dorsal horn early after peripheral nerve injury is associated with damage to primary afferent aβ-fibers. Cells 14(9):666. doi: 10.3390/cells14090666 PMID: 40358190
Objective: To investigate the spatial relationship between microgliosis and the projections of injured nerves by generating mice that had expressed tdTomato in the fourth lumbar dorsal root ganglion (L4-DRG) neurons via intra-L4-spinal nerve (SpN) injection of adeno-associated viral vectors.
Summary: After transection of the L4-SpN, authors found that microgliosis in the SDH selectively occurred in the innervation territories of the injured primary afferent fibers. However, denervating transient receptor potential vanilloid 1 (TRPV1)-expressing primary afferent fibers in theSDH through intrathecal injection of capsaicin did not trigger microgliosis, nor did it influence the microgliosis induced by L4-SpN injury. Conversely, pharmacological damage to myelinated DRG neurons, including Aβ-fibers, was sufficient to induce microgliosis. Furthermore, L4-SpN injury also induced microgliosis in the gracile nucleus, which primarily receives innervation from Aβ-fibers. These findings suggest that microgliosis in the SDH shortly after peripheral nerve injury is predominantly associated with damage to primary afferent Aβ-fibers.
Usage: WT mice were injected with saporin into the L4-SpN, administering 400 nL of saporin solution [saporin conjugated with cholera toxin B subunit (CTB-SAP), isolectin B4 (IB4-SAP),and unconjugated saporin (Ctrl-SAP)]
Related Products: CTB-SAP (Cat. #IT-14), IB4-SAP (Cat. #IT-10), Saporin (Cat. #PR-01)
Optimization of lipid nanoparticles with robust efficiency for the delivery of protein therapeutics to augment cancer immunotherapy
Ren L, Zhao Z, Chao Y, Yu P, Mei Z, Du B, Cheng Y (2025) Optimization of lipid nanoparticles with robust efficiency for the delivery of protein therapeutics to augment cancer immunotherapy. Adv Sci (Weinh) e2500844. doi: 10.1002/advs.202500844 PMID: 40056044
Objective: To develop a family of Lipid Nanoparticles (LNPs) with robust high efficiency in addressing the multiple barriers in cytosolic protein delivery by incorporating clinically approved ionizable lipids into traditional cationic LNPs. The authors investigated the in vivo delivery efficacy of the LNPs using saporin as the model protein.
Summary: The combination of cationic and ionizable lipids enables efficient protein binding and endosomal escape. Optimized LNPs efficiently deliver various proteins, including antibodies, enzymes, toxins, and Cas9 into living cells with reserved functions. The optimized LNPs successfully deliver therapeutic proteins such as saporin and interleukin-10 (IL-10) to inhibit tumor growth in several animal models.
Usage: Cell Viability and Apoptosis Assay: For evaluating in vitro saporin delivery efficacy, 143B cells were incubated with free saporin or saporin/LNP at saporin concentrations ranging from 0 to 61 nm. In Vivo Saporin Delivery by LNP: mice were intravenously injected with 100μL saporin or saporin/LNP once every two days. The doses of saporin and LNP in in vivo experiments were fixed at 50μg kg−1 and 2.4 mg lipid/kg, respectively.
Related Products: Saporin (Cat. #PR-01)
Efficient cytosolic delivery of protein by preorganized amidiniums on pillar[5]arene
Guo S, Xu H, Cheng Z, Wang L, Yang P, Wang R (2025) Efficient cytosolic delivery of protein by preorganized amidiniums on pillar[5]arene. CCL 111022. doi: 10.1016/j.cclet.2025.111022
Objective: To use amidinium functionalized pillar[5]arene (AP5) as a small molecular carrier to facilitate intracellular delivery of proteins with different sizes and isoelectric points.
Summary: The densely preorganized amidinium groups on pillar[5]arene skeleton could not only glue proteins together to form AP5@protein complex through multiple salt-bridges, but also promote cellular internalization AP5@protein complex. The bioactivities of the internalized proteins were well-maintained. This study provides a novel, versatile and macrocyclic-molecule based intracellular protein delivery carrier through the preorganization of amidiniums onpillar[5]arene.
Usage: The AP5@saporin complexes showed significant toxicity toward HeLa cells with an IC50 of 102 nmol/L. However, saporin alone showed minimal toxicity on HeLa cells due to membrane-impermeability of saporin.
Related Products: Saporin (Cat. #PR-01)
Targeted delivery of cytotoxic proteins via lipid-based nanoparticles to primary Langerhans cells
Rahhal N, Rentzsch M, Seiser S, Freystätter C, Elbe-Bürger A, Rademacher C (2025) Targeted delivery of cytotoxic proteins via lipid-based nanoparticles to primary Langerhans cells. Nanoscale doi: 10.1039/d4nr03638g PMID: 39775685
Summary: Saporin was used as a model protein to showcase the potential of delivering intact proteins to Langerhans cells. Authors observed specific killing of cells expressing langerin in vitro, and in primary Langerhans cells isolated from mouse and human skin ex vivo with minimal off target effects.
Related Products: Saporin (Cat. #PR-01)
Guanidyl-rich α-helical polypeptide enables efficient cytosolic pro-protein delivery and CRISPR-Cas9 genome editing
Zhao Z, Zhang H, Li W, Wang Y, Wang Y, Yang H, Yin L, Liu X (2025) Guanidyl-rich α-helical polypeptide enables efficient cytosolic pro-protein delivery and CRISPR-Cas9 genome editing. J Mater Chem B doi: 10.1039/d4tb02009j PMID: 39760520
Objective: To develop an efficient strategy via cationic alpha-helical polypeptide-mediated anionic proprotein delivery.
Summary: The protein was reversibly modified with adenosine triphosphateviadynamic covalent chemistry to prepare an anionic proprotein (A-protein) with abundant phosphate groups. A guanidyl-decorated a-helical polypeptide (LPP) was employed not only to encapsulate A-protein through electrostatic attraction and hydrogen bonding, forming stable nanocomplexes, but also to enhance cell membrane penetration due to its rigid alpha-helical conformation. Consequently, this strategy mediated the effective delivery of various proteins with different isoelectric points and molecular weights, including a-chymotrypsin, bovine serum albumin, ribonuclease A, cytochromeC, saporin, horseradish peroxidase, b-galactosidase, and anti-phospho-Akt, into cancer cells.
Usage: Cytosolic delivery: Saporin, was employed to evaluate LPP-mediated cytosolic delivery and its cancer cell-killing efficacy. The LPP/A-saporin nocomplexes (NCs) caused significant toxicity, with an IC50 value of 0.4ug/mL. In vivo antitumor efficiency of LPP/A-saporin NCs: LPP/A-saporin NCs were administrated by intratumoral injection in HeLa xenograft tumor-bearing mice and their antitumor efficacy was evaluated. When the tumor volume reached B50 mm3, the mice were randomly divided into three groups (6 mice per group) and intratumorally injected with PBS, free saporin, or LPP/A-saporin NCs at 0.1 mg saporin per kg on days 0 and 2.
Related Products: Saporin (Cat. #PR-01)
CD44v, S1PR1, HER3, MET and cancer-associated amino acid transporters are promising targets for the pancreatic cancers characterized using mAb
Nakano T, Okita K, Okazaki S, Yoshimoto S, Masuko S, Yagi H, Kato K, Tomioka Y, Imai K, Hamada Y, Masuko K, Shimada-Takaura K, Nagai N, Saya H, Arai T, Ishiwata T, Masuko T (2025) CD44v, S1PR1, HER3, MET and cancer-associated amino acid transporters are promising targets for the pancreatic cancers characterized using mAb. FEBS Open Bio doi: 10.1002/2211-5463.13963 PMID: 39757718
Objective: To analyze pancreatic ductal adenocarcinomas (PDAC) using novel rat mAbs against membrane proteins in conjunction with flow cytometry and immunohistochemistry
Summary: Internalization of membrane proteins by mAbs and growth inhibition by toxin-linked mAbs were demonstrated in many PDAC cell lines, and mAbs against S1PR1, ASCT2, HER3 and CD44v inhibited the growth of xenografted MIA PaCa-2PDAC cells. Furthermore, CD44v-high PDAC showed high mRNA expression of HER1–3, MET and CD44v, and was correlated with poor prognosis. Taken together, the results suggest that CD44v, S1PR1, HER3, MET and the above-mentioned cancer-associated amino acid transporters might be promising targets for the diagnosis and treatment of PDAC.
Usage: Growth inhibition by rat mAbs against PDAC cell lines with secondary antibodies conjugated to saporin (PR-01). Rat mAb solution (4 ug/mL), a PDAC cell suspension and Saporin-conjugated goat anti-rat IgG pAb (Rat-ZAP, IT-26 at 4 ug/mL) were added to each well of 96-well plates.
Related Products: Saporin (Cat. #PR-01), Rat-ZAP (Cat. #IT-26)
Itaconate facilitates viral infection via alkylating GDI2 and retaining Rab GTPase on the membrane
Yin S, Tao Y, Li T, Li C, Cui Y, Zhang Y, Yin S, Zhao L, Hu P, Cui L, Wu Y, He Y, Yu S, Chen J, Lu S, Qiu G, Song M, Hou Q, Qian C, Zou Z, Xu S, Yu Y (2024) Itaconate facilitates viral infection via alkylating GDI2 and retaining Rab GTPase on the membrane. Signal Transduct Target Ther 9(1):371. doi: 10.1038/s41392-024-02077-8 PMID: 39730330
Objective: To demonstrate that the IRG1-itaconate axis facilitates the infections of vesicular stomatitis virus (VSV) and influenza A virus (IAV) in macrophages and epithelial cells via Rab GTPases redistribution.
Summary: The study reveals that neutrophils-derived itaconate facilitates viral infection via redistribution of Rab GTPases, suggesting potential targets for antiviral therapy.
Usage: Immunofluorescence: cells were fixed in PBS solution containing 4% formaldehyde, permeabilized with 0.2% saporin (PR-01) along with a mixture of 5% BSA and 10% FCS
Related Products: Saporin (Cat. #PR-01)
Phase-separating peptide coacervates with programmable material properties for universal intracellular delivery of macromolecules
Sun Y, Wu X, Li J, Radiom M, Mezzenga R, Verma CS, Yu J, Miserez A (2024) Phase-separating peptide coacervates with programmable material properties for universal intracellular delivery of macromolecules. Nat Commun 15(1):10094. doi: 10.1038/s41467-024-54463-z PMID: 39572548
Objective: To systematically manipulate the sequence of Phase-separating peptides (PSPs) to unravel the relationships between their molecular structure, the physical properties of the resulting coacervate microdroplets (CMs), and their delivery efficacy.
Summary: A few amino acid alterations are sufficient to modulate the viscoelastic properties of CMs towards either a gel-like or a liquid-like state as well as their binding interaction with cellular membranes, collectively enabling to tune the kinetics of intracellular cargo release. The authors also demonstrated that the optimized PSPs CMs display excellent transfection efficiency in hard-to-transfect cells such as primary fibroblasts and immune cells.
Usage: The cytotoxicity of the saporin-loaded (at various concentrations) or pristine CMs were evaluated using the Cell Counting Kit-8 (CCK-8).
Related Products: Saporin (Cat. #PR-01)
Anti-EGFR antibody immunotoxins improve cytotoxic effects in the salivary gland cancer A253 cell line
Kuroda M, Komatsu N, Kosai A, Hamakubo T, Abe T (2024) Anti-EGFR antibody immunotoxins improve cytotoxic effects in the salivary gland cancer A253 cell line. doi: 10.1016/j.ajoms.2024.11.003
Objective: To confirm the antitumor effects of IT-Cetuximab (IT-Cmab= saporin-conjugated anti-EGFR antibody), which is cetuximab conjugated with a toxin, targeting salivary gland cancers—a type of cancer with limited effective treatment options aside from surgery.
Summary: Cmab alone exhibited no cytotoxic effects, but IT-Cmab demonstrated concentration-dependent cytotoxic effects in A253 cells.
Usage: Cytotoxicity assay (@1.34pM to 4.2nM)
Related Products: Saporin (Cat. #PR-01)
