JOURNAL OF CONTROLLED RELEASE
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2023
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IF 10.8
Ziming Lin,Taomei Deng,Yinuo Liu,Shuangyang Zheng,Guangji Wang,Hua He,Jingwei Zhang
Poor tumor penetration is the most significant barrier to the clinical translation of nanomedicines . Despite numerous studies, little is known about how the physicochemical properties and tumor-associated environments impact liposome intratumoral penetration from a multi-factorial perspective. Thus, we developed a set of model liposomes to explore the laws of their intratumoral penetration. Our comprehensive analysis revealed that zeta potential , membrane fluidity, and size of liposomes could influence their penetration in the peripheral, intermediate, or central areas of the tumor, respectively. Moreover, protein corona and stromal cells primarily impeded liposome penetration in the tumor periphery, while the vascular vessels had a similar effect in the tumor center. Our results also revealed a non-monotonic relationship, indicating that the best condition for a single factor may not necessarily be the optimal choice when considering all the factors. The preferred size, zeta potential, and membrane fluidity for excellent tumor penetration are within the ranges of 52–72 nm , 16–24 mV, and 230–320 mp, respectively. Our study provides a comprehensive understanding of the influence of physicochemical properties and tumor-associated environments on liposome intratumoral penetration, offering explicit guidance for the precise design and rational optimization of anti-tumor liposomes.
研究领域:
药学
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纳米技术
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
Small
·
2023
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IF 13.3
Hong Wang,Junbin Gao,Cong Xu,Yuejun Jiang,Meihuan Liu,Hanfeng Qin,Yicheng Ye,Li Zhang,Wanxian Luo,Bin Chen,Lingli Du,Fei Peng,Yingjia Li,Yingfeng Tu
Nanotechnology-based strategy has recently drawn extensive attention for the therapy of malignant tumors due to its distinct strengths in cancer diagnosis and treatment. However, the limited intratumoral permeability of nanoparticles is a major hurdle to achieving the desired effect of cancer treatment. Due to their superior cargo towing and reliable penetrating property, micro-/nanomotors (MNMs) are considered as one of the most potential candidates for the coming generation of drug delivery platforms. Here, near-infrared (NIR)-actuated biomimetic nanomotors (4T1-JPGSs-IND) are fabricated successfully and we demonstrate that 4T1-JPGSs-IND selectively accumulate in homologous tumor regions due to the effective homing ability. Upon laser irradiation, hyperthermia generated by 4T1-JPGSs-IND leads to self-thermophoretic motion and photothermal therapy (PTT) to ablate tumors with a deep depth, thereby improving the photothermal therapeutic effect for cancer management. The developed nanomotor system with multifunctionalities exhibits promising potential in biomedical applications to fight against various diseases.
研究领域:
纳米技术
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癌症治疗
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生物医学工程
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材料科学
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产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2021
·Vol. 14
·期 4
·1271-1284
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IF 7.79
Yongju He,Xingyu Fan,Xiaozan Wu,Taishun Hu,Fangfang Zhou,Songwen Tan,Botao Chen,Anqiang Pan,Shuquan Liang,Hui Xu
Poor tumor penetration is a major obstacle to nanomedicine for achieving effective anticancer therapy. Tumor microenvironment-induced nanomedicine size shrinkage is a promising strategy to overcome the drug penetration barrier across the dense tumor matrix. Herein, we design a size-shrinkable nanocarrier that uses acid as a means of triggering a change in particle size for co-achievement of efficient tumor accumulation followed by deep tumor penetration and rapid clearance from the body. This nanocarrier is constructed from a pH-sensitive lipid layer shell and an ultrasmall amino-functionalized mesoporous silica nanoparticle core capable of loading drugs. After intravenous injection into mice bearing the 4T1 tumor, the nanocarrier with an initial hydrodynamic size of about 33 nm could effectively accumulate at the tumor site through the enhanced permeability and retention effect. Subsequently, in the acidic tumor microenvironment, the lipid layer comprising 9 alkyl-spiropyran (SP-C9) undergoes a volume shrinkage due to the conversion of hydrophobic SP-C9 to amphiphilic 9 alkyl-merocyanine (MC-C9), thus leading to a significant decrease in the entire particle size (hydrodynamic size ∼17 nm) for enhanced intratumoral penetration. Moreover, we find that this size-shrinkable nanocarrier could be rapidly excreted out of the body based on the ICP analysis, significantly reducing biosafety issues. Benefiting from the effective tumor accumulation and penetration of the nanocarrier, the released doxorubicin shows potent antitumor efficacy. This demonstrates the high potential of the designed nanocarrier in solid tumor treatment.
研究领域:
纳米技术
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药学
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癌症治疗
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2025
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IF 9.7
Yaqian He,Zichuang Xu,Yaqian Yan,Jiajun Gao,Xuwu Zhang,Yuchu He,Qingzhi Luo,Desong Wang,Dawei Gao
The crucial challenge of nanodrug systems is their low transfer efficiency, which requires overcoming transmission resistance due to tumour accumulation and intratumoural penetration. In this study, we propose a synergistic strategy involving ‘pioneer’ T cells and ‘main force’ piezo-nanozymes to enhance the ability of T cells and nanodrugs to simultaneously target tumours with high specificity and achieve enhanced immunotherapy. Herein, a mature dendritic cell (DC) membrane was used to encapsulate the piezo-nanozyme MoS 2 to form nanodrugs (MDMs). On the basis of the lymphatic homing ability of mature DCs, MDMs can accumulate in tumour-draining lymph nodes to activate T cells and rivets on T cells. T cells subsequently serve as ‘pioneers’, overcoming circulatory barriers and leading to MDM accumulation in tumours. Furthermore, the piezo-nanozyme MoS 2 acts as the ‘main force’ for reducing tumour interstitial fluid pressure through piezocatalysis, thereby reducing intratumoural penetration resistance and increasing the permeation efficiency of T cells and nanodrugs. Piezocatalysis initiates immunogenic cell death, further enhancing the efficacy of T-cell immune responses, which not only clear the primary tumour but also inhibit tumour metastasis. This study provides a novel strategy and theoretical basis for overcoming biological barriers and improving the effects of chemotherapy and immunotherapy.
研究领域:
纳米医学
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癌症免疫治疗
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生物医学工程
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药物递送系统
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
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2020
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IF 10.317
Jing Yan,Qinghua Wu,Ziyin Zhao,Jianhua Wu,Huan Ye,Qiujun Liang,Zhuchao Zhou,Mengying Hou,Xudong Li,Yong Liu,Lichen Yin
The anticancer performance of nanomedicine is largely impeded by insufficient intratumoral penetration. Herein, tumor microenvironment (TME)-amendatory and self-adaptive nanoclusters (NCs) capable of cancer-associated fibroblasts (CAFs) depletion and size/charge conversion were engineered to mediate light-assisted, hierarchical intratumoral penetration. Particularly, large-sized NCs (~50 nm) were prepared via self-assembly of FAP-α-targeting peptide-modified, 1 O 2 -sensitive polymers, which were further used to envelope small-sized dendrimer (~5 nm) conjugated with Ce6 and loaded with DOX (DC/D). After systemic administration, the NCs efficiently targeted CAFs and generated lethal levels of 1 O 2 upon light irradiation, which depleted CAFs and concomitantly dissociated the NCs to liberate small-sized, positively charged DC/D. Such stroma attenuation and NCs transformation collectively facilitated the delivery of DC/D into deeper regions of CAF-rich tumors, where DOX and 1 O 2 provoked synergistic anti-cancer efficacies. This study provides an effective approach to facilitate the tumor penetration of nanomedicine by concurrently and spatiotemporally reconfiguring the nano-properties and remodeling the TME.
研究领域:
纳米技术
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癌症治疗
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药学
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2020
·
IF 7.727
Meirong Huo,Honglan Wang,Ying Zhang,Han Cai,Pan Zhang,Lingchao Li,Jianping Zhou,Tingjie Yin
Modulation of tumor microenvironment (TME) has been indicated as an approach to improve efficacy of cancer therapy. Here, we proposed a nano co-delivery based combination therapy of paclitaxel (PTX) and silybin (SB) which can employ the synergistic effects through chemotherapy sensitization and microenvironment modulation. A dextran-based amphiphilic polymer (Dex-DOCA) was successfully developed for in vivo co-delivery and thus “synchronizing” the biodistribution , transport and release of PTX and SB. Resultantly, Dex-DOCA exhibited an excellent encapsulating efficiency for both PTX and SB with adjustable loading ratio for an optimal synergistic antitumor activity . Moreover, the co-loaded nanoparticles efficiently discharged the two drugs at the prospective dosage ratio specifically in acid endo/lysosome mimic environments. The results of in vitro cytotoxicity and cell apoptosis assays further confirmed the SB sensitized PTX potency. Finally, in vivo investigation demonstrated that the co-loaded nanoparticles could effectively accumulate in tumor sites by passive targeting, and inhibit tumor growth through an enhanced intratumoral penetration (resulted from stromal components eradication and tumor vessels normalization associated TME modulation), as well as a sensitization effect of SB on PTX cytotoxic chemotherapy .
研究领域:
药学
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肿瘤学
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纳米技术
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
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2021
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IF 12.479
Mengcheng Ma,Yafang Chen,Mingda Zhao,Junhui Sui,Zhihao Guo,Yuedi Yang,Zhiyi Xu,Yong Sun,Yujiang Fan,Xingdong Zhang
Integrating these features of acid-activated positively charged surface and size contraction into single nanoparticle would be an effective strategy for enhancing cellular uptake, intratumoral penetration and accumulation. Here, hierarchical responsive micelle (HVDMs) was developed via RAFT reaction as multifunctional polymer-drug conjugate for maximizing penetration and therapeutic effect against MCF-7 tumor by combining positively charged surface with size contraction: surface zeta-potential reversal (−2 to +12 mV) by protonation of PHEME and size contraction (~81–~41 nm) by simultaneous hydrophobic/hydrophilic conversion (pH ≈ 6.7); the disintegration of hydrazone bond between hydrophobic PVB and DOX triggered drug release (pH ≈ 5.0). The in vitro structural stabilization, cellular uptake and anti-proliferative efficiency were significantly higher than other control groups (CVDMs and HSDMs) at pH 6.7. The markedly increased penetration depth, cellular internalization and anti-tumor efficiency were confirmed in 3D MCSs spheroids at pH 6.7, and the ex vivo DOX fluorescence images further verified obvious penetration and accumulation in internal region of solid tumor. The antitumor effect in vivo demonstrated that HVDMs accelerated tumor atrophy, induced intratumoral cells apoptosis and alleviated system toxicity.
研究领域:
纳米技术
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癌症治疗
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药学科学
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材料科学
✓ 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）