JOURNAL OF CONTROLLED RELEASE
·
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
ADVANCED MATERIALS
·
2025
·
IF 26.8
Jiwei Jiang,Jing Hu,Mingtong Li,Mingzhi Luo,Bin Dong,Metin Sitti,Xiaohui Yan
Peritumoral subcutaneous injection has been highly envisioned as an efficient yet low-risk administration of photothermal agents for superficial tumor photothermal therapy. However, obstructed by complex subcutaneous tissue, the delivery of injected photothermal agents to the specific tumor remains a critical issue. Herein, the study reports a polydopamine (PDA)-encapsulated spherical core/shell nanomotor with fluorescent indocyanine green (ICG) immobilized on its PDA shell. Upon the first near-infrared (NIR-I) irradiation, this motor can generate favorable photothermal heat, and meantime, emit a robust ICG fluorescence in the second near-infrared window (NIR-II). The heat turns the motor into an active photothermal agent able to perform thermophoretic propulsion along the irradiation direction in subcutaneous tissue, while the ICG fluorescence can direct the subcutaneous propulsion of motors toward specific tumor through real-time NIR-II imaging. These functions endow the motor with the ability of moving to tumor after being injected at peritumoral site, enabling an enhanced photothermal therapy (PTT). The results demonstrated herein suggest an integrated nanorobotic tool for the superficial PTT using peritumoral administration, highlighting an NIR-II imaging-directed subcutaneous propulsion.
研究领域:
生物医学工程
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纳米技术
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癌症治疗
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医学影像
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产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2023
·Vol. 15
·期 8
·2157
·
IF 5.4
Hongshuang Wan,Shuangqing Wang,Chuying Li,Bowen Zeng,Hao Wu,Chao Liu,Liqing Chen,Mingji Jin,Wei Huang,Yingda Zang,Dongming Zhang,Zhonggao Gao,Zhehu Jin
A keloid is a benign tumor manifested as abnormal fibroplasia on the surface of the skin. Curing keloids has become a major clinical challenge, and searching for new treatments and medications has become critical. In this study, we developed a LA67 liposome-loaded thermo-sensitive hydrogel (LA67-RL-Gel) with active targeting for treating keloids via peritumoral injection and explored the anti-keloid mechanism. Firstly, Arg-Gly-Asp (RGD) peptide-modified liposomes (LA67-RL) loaded with LA67 were prepared with a particle size of 105.9 nm and a Zeta potential of −27.4 mV, and an encapsulation efficiency of 89.6 ± 3.7%. We then constructed a thermo-sensitive hydrogel loaded with LA67-RL by poloxamer 407 and 188. The formulation was optimized through the Box–Behnken design, where the impact of the proportion of the ingredients on the quality of the hydrogel was evaluated entirely. The optimal formulation was 20.7% P407 and 2.1% P188, and the gelation time at 37 °C was 9.5 s. LA67-RL-Gel slowly released 92.2 ± 0.8% of LA67 at pH 6.5 PBS for 72 h. LA67-RL-Gel increased adhesion with KF cells; increased uptake; promoted KF cells apoptosis; inhibited cell proliferation; reduced α-SMA content; decreased collagen I, collagen III, and fibronectin deposition; inhibited angiogenesis; and modulated the keloid microenvironment, ultimately exerting anti-keloid effects. In summary, this simple, low-cost, and highly effective anti-keloid liposome hydrogel provides a novel approach for treating keloids and deserves further development.Keywords:keloid;in situ hydrogel;pluronic;triptolide;Arg-Gly-Asp
研究领域:
药剂学
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材料科学
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生物医学工程
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皮肤科
✓ 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）