RSC Advances
·
2016
·Vol. 6
·期 103
·100984-100992
·
IF 3.289
Mengshi Yang,Di Jiang,Zhilong Chen,Jun Chen
Photodynamic therapy (PDT) does well in both curing early stage tumors and improving patients’ quality of life. However, the limited selectivity of photosensitizers (PSs) to tumors has become an urgent issue during the application of PDT clinically, which would exhibit a poor therapeutic outcome and induce skin phototoxicity. To solve this problem, PS-loaded D-α-tocopheryl polyethylene glycol succinate (vitamin E TPGS, or simply TPGS) nanoparticles with tumor homing and penetrating peptide tLyp-1 decoration (t-NP) were constructed for PDT of tumors in this study. Verteporfin (VP), as an effective PS, was encapsulated in the core of t-NP, and tLyp-1 was functionalized on the surface as a functional ligand to increase vascular permeability and target the tumor cells. These nanoparticles were spherical in shape and exhibited a narrow size distribution of 23.3 ± 0.80 nm, and had a high encapsulation efficiency and loading capacity of hydrophobic VP. Compared with unmodified nanoparticles (NP), t-NP exhibited enhanced cellular uptake in both primary human umbilical vein endothelial cells (HUVECs) and drug-resistant human colon adenocarcinoma cells (HCT15); and t-NP showed higher selectivity to HCT15 tumors in vivo after intravenous administration of the same dose of VP. The anti-tumor experiment in vivo strongly indicated that nanoparticles with tLyp-1 peptide modification can enhance the selectivity of the PS, and improve the PDT effect.
研究领域:
药剂学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
ACS Nano
·
2022
·
IF 18.027
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
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 in vivo orthotopic and ectopic TNBC therapy confirmed the efficient tumor inhibition of ICG@HSA-Azo-HP after dual-stage irradiation. The synergistic penetration strategy of on-demanded size-shrinkage and ligand guidance accompanied by clinically feasible NIR irradiation provides a promising approach for deep-penetrating TNBC therapy.
研究领域:
肿瘤学
·
纳米医学
·
光疗
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）