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The excellent biocompatibility drug delivery system for effective treatment of glioma is still greatly challenged by the existence of blood-brain barrier, blood-brain tumor barrier, and the tissue toxicity caused by chemotherapy drugs. In this study, poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) is used for the first time for modifying third-generation poly(amidoamine) (PAMAM) to enhance their brain tumor-targeted drug delivery ability as well as simultaneously reducing the toxicity of PAMAM dendrimers and the tissue toxicity of the loaded doxorubicin (DOX). The cytotoxicity, the therapeutic ability in vitro, and the brain tumor-targeted ability of the PMPC modified PAMAM nanoparticles are further studied. Results indicate that PMPC, as a dual-functional modifier, can significantly reduce the cytotoxicity of PAMAM dendrimers, while efficiently target the brain tumor. In addition, the therapeutic effect of DOX-loaded PAMAM-PMPC in mice inoculated with U-87 is also studied in vivo. In comparison with DOX solution, DOX-loaded PAMAM-PMPC alleviates weight loss of tumor-inoculated mice and reduces the cardiotoxicity of DOX. The tumor growth inhibition, in vivo, is significantly increased up to (80.76 ± 1.66)%. In conclusion, this strategy of PMPC dual-functional targeted nanocarrier provides a new method for the delivery of chemotherapeutic drugs to treat glioma.
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http://dx.doi.org/10.1002/mabi.202000392 | DOI Listing |
Adv Healthc Mater
September 2025
Brain Center, Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, School of Pharmaceutical Sciences, Wuhan University, Wuhan, Hubei, 430071, China.
Glioblastoma multiforme (GBM) continues to pose a significant challenge in the field of neuro-oncology primarily because of the limited penetration of therapeutics across the blood-brain barrier (BBB) and the presence of immunosuppressive tumor microenvironments. To address these challenges, a HD-PEG@BM biomimetic nanoplatform (hereinafter referred to as HD-P@BM) is developed that cloaks the near-infrared II photosensitizer HD-PEG (HD-P) inside microglial membranes to enable enhanced BBB penetration and tumor-targeted delivery. In this study, it is found that the microglia-derived membranes enhanced the uptake of nanoparticles by both the glioma cells and tumor-associated microglia.
View Article and Find Full Text PDFNanoscale
July 2025
Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran.
Glioblastoma, a primary brain tumor, is the most prevalent and destructive intracranial tumor, and its therapeutics are restricted by insufficient doses and toxicity, resulting from classical drug delivery systems using passive delivery. Active drug delivery approaches using tumor-targeted nanomotors with the ability to actively bypass the blood-brain barrier (BBB) can enhance the permeability and accumulation of carried drugs into the brain tumors. Nanomotors show self-propelled motion that enables them to autonomously navigate within biological fluids and efficiently penetrate across the blood vessels and BBB, thereby reducing systemic side effects and improving the efficacy of the administered dosage in the brain tumor.
View Article and Find Full Text PDFSci Transl Med
July 2025
San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
Chimeric antigen receptor (CAR) T cells have shown limited efficacy against solid tumors because of poor tissue penetration, constrained activity, and early exhaustion due to the immunosuppressive tumor microenvironment (TME). Although stimulatory cytokines can counteract immune suppression, their systemic administration entails risk of toxicities and counter-regulatory responses. Here, we leveraged a population of tumor-associated TIE2-expressing macrophages (TEMs) to release interferon-α (IFN-α) and/or orthogonal interleukin-2 (oIL2) at the tumor site.
View Article and Find Full Text PDFJ Nanobiotechnology
June 2025
Neuroscience Research Center, Taipei Medical University Hospital, Taipei, 11031, Taiwan.
Background: Metastasis of medulloblastomas (MBs) is difficult to treat and remains the primary cause of death in children with this brain tumor. Current treatment focuses on radiotherapy to limit metastatic recurrence and maintain survival, but this may cause long-term neurocognitive deficits. This challenge emphasizes the need for novel targeted therapies to combat metastatic MB.
View Article and Find Full Text PDFJ Radiosurg SBRT
January 2025
Department of Neurological Surgery, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA.
Background: Secondary trigeminal neuralgia (TN) is often associated with benign meningiomas and schwannomas. For patients who are unable to undergo surgical resection, Gamma Knife radiosurgery (GKRS) is a well-established alternative for tumor control. There is limited data on the pain outcomes in these patients undergoing tumor-targeted GKRS.
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