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Self-Adaptive Nanocarriers Overcome Multiple Physiological Barriers to Boosting Chemotherapy of Orthotopic Pancreatic Cancer.
ACS Nano
January 2025
School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou 511442, P. R. China.
Chemotherapy is the primary treatment option for pancreatic cancer, although nanocarrier-based drug delivery systems often struggle with multiple physiological barriers, limiting their therapeutic efficacy. Here, we developed a pH/reactive oxygen species (ROS) dual-sensitive self-adaptive nanocarrier (DAT) encapsulating camptothecin (CPT), an analog of the pancreatic chemotherapeutic drug irinotecan (CPT-11), to enhance chemotherapy outcomes in orthotopic pancreatic cancer by addressing multiple physiological barriers. The nanocarrier features a peripherally positively charged arginine (Arg) residue on DAT and is masked with an acid-labile 2,3-dimethylmaleic anhydride (DA) to improve circulation time.
View Article and Find Full Text PDFHydroxyl-based acid-hypersensitive acetal ester bond: Design, synthesis and the application potential in nanodrugs.
Eur J Med Chem
February 2025
State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China. Electronic address:
Article Synopsis
- Targeted drug delivery systems are utilizing the acidic environment of tumors to improve drug stability and reduce toxicity through modifications like hydroxyl groups.
- A newly developed "acetal ester bond" offers a highly sensitive and easy-to-synthesize linkage that allows for efficient drug release specifically in acidic conditions while maintaining stability in healthy physiological environments.
- The acetal ester bond-based paclitaxel conjugate (PTX-COU) demonstrated superior tumor growth inhibition in experiments, suggesting its potential for enhancing targeted drug delivery and minimizing systemic side effects.
Two-pronged reversal of chemotherapy resistance by gold nanorods induced mild photothermal effect.
Bioeng Transl Med
September 2024
School of Biomedical Engineering, Shanghai Jiao Tong University Shanghai People's Republic of China.
Chemotherapy treatment outcomes are severely restricted by multidrug resistance (MDR), in which tumors develop a multiple cross-resistance toward drug involving the pump and nonpump resistance mechanisms, resulting in drug efflux and defending against drug toxicity. Herein, we constructed a pH and near infrared (NIR) light responsive nanomedicine DOX@FG based on gold nanorods (GNRs) that demonstrated the potential to improve chemotherapy outcomes by overcoming MDR. DOX@FG was constructed by conjugating folic acid (FA) and doxorubicin (DOX) derivatives onto GNRs, where the DOX derivatives possessed an acid-labile hydrazone bond.
View Article and Find Full Text PDFpH-Sensitive Amphiphilic Diblock Polyphosphoesters with Lactate Units: Synthesis and Application as Drug Carriers.
Int J Mol Sci
April 2024
Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641, Yamazaki, Noda 278-8510, Chiba, Japan.
pH-sensitive amphiphilic diblock polyphosphoesters containing lactic acid units were synthesized by multistep one-pot polycondensation reactions. They comprise acid-labile P(O)-O-C and C(O)-O-C bonds, the cleavage of which depends on the pH of the medium. The structure of these copolymers was characterized by H, C {H}, P NMR, and size exclusion chromatography (SEC).
View Article and Find Full Text PDFmass spectrometry-based biodistribution analysis of an antibody-Resiquimod conjugate bearing a protease-cleavable and acid-labile linker.
Front Pharmacol
December 2023
Chemistry Department, Università degli Studi di Milano, Milano, Italy.
Article Synopsis
- - Immune-stimulating antibody conjugates (ISACs) use imidazoquinoline (IMD) payloads to activate the immune system against cancer cells, resulting in prolonged anticancer effects.
- - A new ISAC was developed with Resiquimod (R848), a specific antibody for Carbonic Anhydrase IX (CAIX), and a special linker designed to release the drug in the presence of certain enzymes and acidic environments.
- - Stability tests revealed that while the linker can break down, the IgG antibody effectively targets tumors and remains in circulation for an extended period, indicating its potential for targeted cancer therapy.
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