Photo-Electro Active Nanocomposite Silk Hydrogel for Spatiotemporal Controlled Release of Chemotherapeutics: An In Vivo Approach toward Suppressing Solid Tumor Growth
| Autor: | Praveen Kumar Jadi, Basveshwar Gawali, Ankit Gangrade, Biman B. Mandal, Vegi Ganga Modi Naidu |
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| Rok vydání: | 2020 |
| Předmět: |
Materials science
Photochemistry Nanogels Biocompatible Materials 02 engineering and technology 010402 general chemistry 01 natural sciences Drug Delivery Systems In vivo Neoplasms medicine Animals Humans General Materials Science Doxorubicin Cardiotoxicity Nanocomposite technology industry and agriculture Hydrogels 021001 nanoscience & nanotechnology Controlled release 0104 chemical sciences SILK Apoptosis Drug delivery Biophysics 0210 nano-technology medicine.drug |
| Zdroj: | ACS applied materialsinterfaces. 12(25) |
| ISSN: | 1944-8252 |
| Popis: | Conventional systemic chemotherapeutic regimens suffer from challenges such as nonspecificity, shorter half-life, clearance of drugs, and dose-limiting toxicity. Localized delivery of chemotherapeutic drugs through noninvasive spatiotemporally controllable stimuli-responsive drug delivery systems could overcome these drawbacks while utilizing drugs approved for cancer treatment. In this regard, we developed photoelectro active nanocomposite silk-based drug delivery systems (DDS) exhibiting on-demand drug release in vivo. A functionally modified single-walled carbon nanotube loaded with doxorubicin (DOX) was embedded within a cross-linker free silk hydrogel. The resultant nanocomposite silk hydrogel showed electrical field responsiveness and near-infrared (NIR) laser-induced hyperthermal effect. The remote application of these stimuli in tandem or independent manner led to the increased thermal and electrical conductivity of nanocomposite hydrogel, which effectively triggered the intermittent on-demand drug release. In a proof-of-concept in vivo tumor regression study, the nanocomposite hydrogel was administered in a minimally invasive way at the periphery of the tumor by covering most of it. During the 21-day study, drastic tumor regression was recorded upon regular stimulation of nanocomposite hydrogel with simultaneous or individual external application of an electric field and NIR laser. Tumor cell death marker expression analysis uncovered the induction of apoptosis in tumor cells leading to its shrinkage. Heart ultrasound and histology revealed no cardiotoxicity associated with localized DOX treatment. To our knowledge, this is also the first report to show the simultaneous application of electric field and NIR laser in vivo for localized tumor therapy, and our results suggested that such strategy might have high clinical translational potential. |
| Databáze: | OpenAIRE |
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