SAUDI PHARMACEUTICAL JOURNAL
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2024
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IF 3
Yao Yao,Qian Zhao,Feng Xu,Tingting Yao
Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide. Sorafenib (Sf) is currently the first-line treatment for HCC. However, due to the side effects and unsatisfied efficiency of Sf, it is urgent to combine different therapeutic agents to inhibit HCC progression and increase the therapeutic efficacy. Here, our study constructed a Sf and KIAA1199-siRNA co-loaded liposome Sf-Lp-KIAA, which was prepared by electrostatic interaction of KIAA1199-siRNA and Sf loaded liposome (Sf-Lp). The particle size, zeta potential, the in vitro cumulative release was investigated. The physical and chemical properties were characterized, and the inhibition of HepG2 growth and metastasis in vitro was investigated. The cellular uptake of the co-loaded liposome was significantly higher than that of free siRNA, and the drug/siRNA could be co-delivered to the target cells. Sf-Lp-KIAA could significantly inhibit the growth, migration, invasion and down-regulate KIAA1199 expression of HepG2 cells in vitro than that of single Sf treated group. In addition, the co-delivery liposome accumulated in the HepG2 subcutaneous tumor model and suppress tumor growth after systemic administration without induce obvious toxicity. The present study implied that the co-delivery of Sf and KIAA1199-siRNA through the co-loaded liposomes exerted synergistic antitumor effects on HCC, which would lay a foundation for HCC therapy in the future.
研究领域:
肿瘤学
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药学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2022
·
IF 11.467
Zhen Wang,Bixi Ding,Yuanpei Zhao,Yue Han,Yu Sheng,Ling Tao,Xiangchun Shen,Jianping Zhou,Lei Jiang,Yang Ding
Increasing knowledge of drug delivery properties, tumor profiles and their relationship promotes precise administration regimens, representing a promising pattern to personalized tumor treatment. Herein, we propose a regulatory hydrogel depot toward metastatic cancer by establishing mathematical models between tumor characteristics and administration regimens. Specifically, a thermo-sensitive PLGA-PEG-PLGA polymer is introduced as injectable hydrogel matrix, of which the administration volume and frequency are manipulated elaborately according to tumor size and gel-degradation kinetics. Structurally, doxorubicin (Dox) and arginine-terminated nanoparticles containing KIAA1199 specific shRNA ( shKIAA RPDNs) are incorporated into hydrogels, thereby formulating a topical and sustained drug depot to achieve synergy treatment. For dual-targeting therapy, Dox interdicts DNA replication/transcription, and shKIAA persistently silences KIAA1199 protein to modulate aggressive phenotypes. After individual peritumoral injection, Gel/ shKIAA RPDNs/Dox demonstrates desirable distribution patterns and gel degradation kinetics with enhanced tumor penetration. Moreover, a preferable inhibition of tumor proliferation and metastasis is confirmed after twice treatment in 12 days, indicating better therapeutic efficacy with less dosage and frequency. Consequently, the controllable administration regimen inspired mathematical models of thermosensitive hydrogel provides an intelligent platform for personalized treatment to metastatic cancer.
研究领域:
肿瘤学
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药学
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生物医学工程
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2018
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IF 7.877
Qiuling Dong,Huaqing Zhang,Yue Han,Aouameur Djamila,Hao Cheng,Zhiyuan Tang,Jianping Zhou,Yang Ding
Metastatic cancer is difficult to defeat with current treatments due to lack of etiological therapeutics and efficient delivery platforms. Employing tumor microenvironment in programming intelligent nanosystems has attracted considerable attention for combinative antitumor therapy. Herein, we proposed a core-shell based drug depot consisting of micellar core and crosslinked-gel shell for site-specific shuttling of paclitaxel (PTX) and KIAA1199 specific shRNA (shKIAA). Poly (e-caprolactone) were grafted with branched polyethylenimine (PEI-PCL) as micellar core, into which hydrophobic PTX was embedded; while shKIAA, a reliable RNAi regimen for metastatic cell inhibition was condensed with PEI through electrostatic interaction ; and then photo-crosslinked hyaluronic acid (m-HA) was further coated as shell. The nanoscale drug depot shared HAase-triggered charge switching and desirable release profile. Upon reaching tumor region, HA shell was degraded by concentrated HAase , and facilitated drug shuttling to individual subcellular targeting site. Rapid intracellular trafficking of micellar core achieved endo/lysosomal escape and cytoplasmic liberation. The half-maximal inhibitory concentration (IC 50 ) of “nanodepot” toward human breast cancer cell line MDA-MB-231 was 0.016 μg/mL (PTX concentration), approximately 3-fold decrease compared to that of monotherapy group (0.043 μg/mL). The tumor weight inhibition (TWI) is 83.30% in xenografted MDA-MB-231 tumor model and metastasis was effectively inhibited in 4T1 orthotopic tumors. Moreover, knockdown of KIAA1199 via sustainable RNAi affected a broad range of cellular functions including apoptosis , migration and invasion. Collectively, tumor environment differentiated spatiotemporal co-delivery fashion holds a great promise for combinative treatment with enhanced efficacy on metastatic cancer cases.
研究领域:
肿瘤学
·
药剂学
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纳米技术
·
分子生物学
✓ 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）