This review presents the present-day literature on the anatomy and physiological mechanisms of the blood-brain barrier and the problematic of cerebral drug delivery in relation to malignant brain tumors. First step in treatment of malignant brain tumors is resection, but there is a high risk of single remnant infiltrative tumor cells in the outer zone of the brain tumor. These infiltrative single-cells will be supplied by capillaries with an intact BBB as opposed to the partly leaky BBB found in the tumor tissue before resection. Even though BBB penetrance of a chemotherapeutic agent is considered irrelevant though the limited success rate for chemotherapeutic treatability of GBM tumors indicate otherwise. Therefore drug delivery strategies to cerebral cancer after resection should be tailored to being able to both penetrate the intact BBB and target the cancer cells. In this review the intact bloodbrain barrier and cerebral cancer with main focus on glioblastoma multiforme (GBM) is introduced. The GBM induced formation of a blood-tumor barrier and the consequences hereof is described and discussed with emphasis on the impact these changes of the BBB has on drug delivery to GBM. The most commonly used drug carriers for drug delivery to GBM is described and the current drug delivery strategies for glioblastoma multiforme including possible routes through the BBB and epitopes, which can be targeted on the GBM cells is outlined. Overall, this review aims to address targeted drug delivery in GBM treatment when taking the differing permeability of the BBB into consideration.
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http://dx.doi.org/10.2174/1381612822666160726113907 | DOI Listing |
ACS Appl Mater Interfaces
January 2025
Department of Radiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, Guangdong 510060, P. R. China.
The clinical application of tyrosine kinase inhibitors (TKIs) is rapidly growing and has emerged as a cornerstone in the treatment of both solid tumors and hematologic malignancies. However, resistance to TKI targets and disease progression remain inevitable. Nanocarrier-mediated delivery has emerged as a promising strategy to overcome the limitations of the TKI application.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
The Ca/calmodulin-dependent protein kinase II α (CaMKIIα) plays a crucial role in regulating neuronal signaling and higher brain functions, being involved in various brain diseases. Utilization of small molecules targeting the CaMKIIα hub domain has proved to be a promising strategy for specific CaMKIIα modulation and future therapy. Through an structure-based virtual screening campaign, we herein identified 2-arylthiazole-4-carboxylic acids as a new class of high-affinity CaMKIIα hub ligands.
View Article and Find Full Text PDFACS Nano
January 2025
Institute of Nanobiomaterials and Immunology & Zhejiang Provincial Key Laboratory of Plant Evolutionary Ecology and Conservation, School of Life Sciences, Taizhou University, Zhejiang Taizhou 318000, China.
Despite significant progress in cancer treatment, traditional therapies still face considerable challenges, including poor targeting, severe toxic side effects, and the development of resistance. Recent advances in biotechnology have revealed the potential of bacteria and their derivatives as drug delivery systems for tumor therapy by leveraging their biological properties. Engineered bacteria, including , , and , along with their derivatives─outer membrane vesicles (OMVs), bacterial ghosts (BGs), and bacterial spores (BSPs)─can be loaded with a variety of antitumor agents, enabling precise targeting and sustained drug release within the tumor microenvironment (TME).
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2025
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, People's Republic of China.
Carrier-free nanomedicines exhibited significant potential in elevating drug efficacy and safety for tumor management, yet their self assembly typically relied on chemical modifications of drugs or the incorporation of surfactants, thereby compromising the drug's inherent pharmacological activity. To address this challenge, we proposed a triethylamine (TEA)-mediated protonation-deprotonation strategy that enabled the adjustable-proportion self assembly of dual drugs without chemical modification, achieving nearly 100% drug loading capacity. Molecular dynamic simulations, supported by experiment evidence, elucidated the underlying self-assembly mechanism.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Department of Surgery, Center for Cancer Medicine, the Fourth Affiliated Hospital of School of Medicine, International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, 322000, China.
Irreversible electroporation (IRE) is a novel local tumor ablation technique that can potentially stimulate immune responses. However, IRE alone cannot effectively activate the immune system or prevent distant metastases. Therefore, this study utilized the biocompatibility of Chlorella vulgaris (C.
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