Advanced Healthcare Materials
·
2020
·Vol. 10
·期 3
·2001029
·
IF 7.367
Shuo Huang,Linlin Zhang,Miaomiao Xu,Chao Li,Hongliang Fu,Jie Huang,Xin Jin,Sheng Liang,Hui Wang
New radionuclide-labeled targeting nanocarrier systems have generated new opportunities for tumor treatment and imaging. Nevertheless, such therapeutic strategy is clinically unfeasible on anaplastic thyroid carcinoma (ATC) patients, because of lacking suitable targets and resistance to radiation. In order to figure out a potential treatment, immuno-histochemical staining is performed in human ATC tissue species and high expression of cluster determinant 44 (CD44) is found. Therefore, a CD44-targeted delivery system is designed and constructed by self-assembly of tyrosine (Tyr)–hyaluronic acid (HA)–polyethyleneimine (PEI), which can radiolabel 131/125 I and load a p53 mutant restoring regent, Prima-1. The 125 I-labeled nanocomposites display an impressive tumor imaging as well as a long radiation treatment cycle. The 131 I-labeled nanoparticles show remarkable anti ATC-tumor effects in vitro and in vivo, due to radiosensitization of Prima-1 by reactivation of the p53 mutants.
研究领域:
纳米技术
·
肿瘤学
·
放射学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Ke Gong,Jiangtao Lin,Xiaoyan Chen,Yi Duan,Jiali Zhang,Jian Yu,Jing Wang,Ruifang Sun,Jie Li,Yourong Duan
In esophageal cancer (EC), clinical specimen testing has uncovered a significant increase in BTB and CNC homolog 1 (BACH1) expression and a shift towards an immunosuppressive environment, alongside a notable decrease in p53 protein expression. Therefore, therapeutic strategies focusing on BACH1 inhibition and p53 upregulation appear promising. Traditional oral treatments for EC lack precision and efficacy. Here, we propose a novel approach employing tumor-targeted nanoparticles (NPs) for drug delivery. However, the formation of a drug reservoir at the esophageal site, crucial for the sustained release of therapeutics, presents significant challenges in nano-delivery systems for EC treatment. To address this, we developed a thermosensitive hydrogel composed of F127 and tannic acid, serving as a vehicle for NP loading. These NPs, synthesized through the emulsion/volatization methods of mPEG-PLGA-PLL-cRGD, facilitate in situ drug delivery. Upon contacting esophageal tissue, the hydrogel transitions to a gel, adhering to the lining and enabling sustained release of encapsulated therapeutics. The formulation encompasses NPs laden with small interfering RNA targeting BACH1 (siBACH1) and the p53 activator PRIMA-1, creating a cohesive gel-nano system. Preliminary biological assessments demonstrate that this injectable, thermosensitive gel-nano system adheres effectively to esophageal tissue and targets EC cells. For better modeling clinical outcomes, a patient-derived organoid xenograft (PDOX) model was innovated, involving transplantation of EC-derived organoids into humanized mice, reconstructed with peripheral blood mononuclear cells (PBMCs). Post-treatment analysis showed substantial EC growth inhibition (89.51% tumor inhibition rate), significant BACH1 level reduction, restored anti-tumor immune responses, and pronounced tumor apoptosis. In summary, our study introduces a thermosensitive gel-nano system for EC treatment via restoring p53 activity and boosting T-cell immunity, with potential for clinical application.
研究领域:
肿瘤学
·
药学
·
生物技术
·
免疫学
✓ 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）