In situ hydrogelation of bicalutamide-peptide conjugates at prostate tissue for smart drug release based on pH and enzymatic activity
| Autor: | Wenying Zhong, Can Wu, Suyun He, Leixia Mei, Mingtao Tao, Ziran Zhai, Keming Xu |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Drug Bicalutamide Cell Survival media_common.quotation_subject 02 engineering and technology 010402 general chemistry 01 natural sciences Tosyl Compounds Mice Prostate cancer Drug Delivery Systems DU145 Prostate Cell Line Tumor Nitriles medicine Animals Humans Anilides Histidine General Materials Science media_common Chemistry Esterases Temperature Hydrogels Hydrogen-Ion Concentration 021001 nanoscience & nanotechnology medicine.disease Rats 0104 chemical sciences Zinc medicine.anatomical_structure Delayed-Action Preparations Self-healing hydrogels Cancer cell Drug delivery NIH 3T3 Cells Biophysics 0210 nano-technology Oligopeptides medicine.drug |
| Zdroj: | Nanoscale. 11:5030-5037 |
| ISSN: | 2040-3372 2040-3364 |
| DOI: | 10.1039/c8nr10528f |
| Popis: | Tissue-specific self-assemblies of supramolecular hydrogels have attracted great interest in material design and biomedical applications, for in situ-formed hydrogels serve as an excellent local depot with tunable release of drug therapeutics. Here we report the design and syntheses of a novel class of histidine-containing hexapeptide derivatives (Nap-1 and ID-1) for in situ hydrogelation at the zinc ion-rich prostate tissue. Thanks to the efficient co-ordination between zinc and histidine, both Nap-1 and ID-1 displayed excellent self-assembly capability with a high sensitivity to zinc ions at ∼0.1 equivalency. To foster a prostate-specific drug delivery system (DDS), ID-1 was chosen for further conjugation with bicalutamide (BLT), a clinically used drug for prostate cancer. The as-synthesized ID-1-BLT retained the self-assembly capability with zinc ions, and conferred supramoelcular hydrogels at the prostate site. Interestingly, ID-1-BLT hydrogels demonstrated tunable drug release profiles in a typical tumor microenvironment, with acidic pH and esterase activity regulating the drug release in a dose dependent manner. Consequently, the hydrogel-based DDS demonstrated enhanced potency and selective cytotoxicity against prostate cancer cell DU145 over normal fibroblast cell NIH3T3, plausibly due to differential cellular uptake of drugs as well as the elevated esterase activities in cancer cells. Finally, the biocompatible hydrogel system demonstrated sustained delivery of drugs at the prostate gland of rats, with a superior in situ drug distribution profile compared to that of aqueous solution of BLT alone. |
| Databáze: | OpenAIRE |
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