Dual-Stage Irradiation of Size-Switchable Albumin Nanocluster for Cascaded Tumor Enhanced Penetration and Photothermal Therapy
| Autor: | Peiying He, Qi Lei, Bin Yang, Tongyi Shang, Jianjun Shi, Qing Ouyang, Wei Wang, Liecong Xue, Fanhui Kong, Zeyu Li, Junda Huang, Lihan Liu, Jimin Guo, C. Jeffrey Brinker, Kaisheng Liu, Wei Zhu |
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| Rok vydání: | 2022 |
| Předmět: |
Indocyanine Green
Mice Inbred BALB C Photothermal Therapy General Engineering General Physics and Astronomy Serum Albumin Human Triple Negative Breast Neoplasms Hyperthermia Induced Phototherapy Ligands Mice Albumins Cell Line Tumor Tumor Microenvironment Animals Humans Nanoparticles General Materials Science |
| Zdroj: | ACS Nano. 16:13919-13932 |
| ISSN: | 1936-086X 1936-0851 |
| DOI: | 10.1021/acsnano.2c02965 |
| Popis: | The triple-negative breast cancer (TNBC) microenvironment makes a feature of aberrant vasculature, high interstitial pressure, and compact extracellular matrix, which combine to reduce the delivery and penetration of therapeutic agents, bringing about incomplete elimination of cancer cells. Herein, employing the tumor penetration strategy of size-shrinkage combined with ligand modification, we constructed a photothermal nanocluster for cascaded deep penetration in tumor parenchyma and efficient eradication of TNBC cells. In our approach, the photothermal agent indocyanine green (ICG) is laded in human serum albumin (HSA), which is cross-linked by a thermally labile azo linker (VA057) and then further modified with a tumor homing/penetrating tLyP-1 peptide (HP), resulting in a TNBC-targeting photothermal-responsive size-switchable albumin nanocluster (ICG@HSA-Azo-HP). Aided by the enhanced permeability and retention effect and guidance of HP, the ca. 149 nm nanoclusters selectively accumulate in the tumor site and then, upon mild irradiation with the 808 nm laser, disintegrate into 11 nm albumin fractions that possess enhanced intratumoral diffusion ability. Meanwhile, HP initiates the CendR pathway among the nutrient-deficient tumor cells and facilitates the transcellular delivery of the nanocluster and its disintegrated fractions for subsequent therapy. By employing this size-shrinkage and peptide-initiated transcytosis strategy, ICG@HSA-Azo-HP possesses excellent penetration capabilities and shows extensive penetration depth in three-dimensional multicellular tumor spheroids after irradiation. Moreover, with a superior photothermal conversion effect, the tumor-penetrating nanocluster can implement effective photothermal therapy throughout the tumor tissue under a second robust irradiation. Both |
| Databáze: | OpenAIRE |
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