CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Jiahao Liu,Qingnian Li,Hanyu Tu,Jie Feng,Xiaofei Fan,Ze Mi,Hongpei Han,Xiaoqian Ma,Qi Liang,Zheng Zhang,Hongshuai Hou,Pengfei Rong,Wenhu Zhou
Radiotherapy is a cornerstone in the treatment of malignant tumors, yet its efficacy is often hindered by intrinsic and acquired resistance mechanisms, notably limited radiation availability and tumor hypoxia within inner tumor region. This study introduces a multifunctional nanosensitizer, CD Bi,Mn-FA @CaP, with high tumor accumulation and deep penetration capabilities via dynamic conformational change. CD Bi,Mn-FA was bismuth manganese-doped carbon dots, offering radiosensitizing properties and catalase-like activity for oxygen generation. Folic acid modification further enhances tumor cell targeting. These carbon dots are encapsulated in calcium phosphate nanoparticles to form CD Bi,Mn-FA @CaP, which demonstrates improved in vivo circulation and tumor accumulation via the enhanced permeability and retention (EPR) effect. Upon encountering the acidic tumor microenvironment, the encapsulation degrades, releasing smaller CD Bi,Mn-FA particles that deeply penetrate tumor tissues. In vitro and in vivo experiments establish that CD Bi,Mn-FA @CaP effectively targets tumor tissue, enhances radiotherapy-induced apoptosis, and suppresses tumor growth. Notably, the nanoparticle achieves a 40 % tumor cure rate and ensures 100 % survival within 45 days post-treatment. Biocompatibility studies confirm minimal systemic impact, with efficient renal and fecal elimination, indicating promising clinical translational potential. This study introduces a novel radiation therapy sensitization strategy and underscores the potential of such size changeable nanoparticles as an advanced targeted drug delivery system for tumors.
研究领域:
生物医学工程
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肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
Acta Biomaterialia
·
2021
·
IF 8.947
Jianping Li,Yashi Wang,Chaoqun Xu,Qianwen Yu,Xuhui Wang,Hanbing Xie,Lifeng Tian,Yue Qiu,Rong Guo,Zhengze Lu,Man Li,Qin He
The dilemma of tumor accumulation and deep penetration has always been a barrier in antitumor therapy. Stimuli-responsive size changeable drug delivery systems provide possible solutions. Nevertheless, the low size-shrinkage efficiency limited the antitumor effects. In this study, an instant pH-responsive size shrinkable nanoassemblies named self-aggregated DOX@HA-CD (SA-DOX@HA-CD) was formulated using small-sized hyaluronic acid modified carbon dots (HA-CD) as monomers , which could self-aggregate into raspberry-like structure via hydrophobicity force in neutral pH and rapidly disassemble into shotgun-like DOX-loaded CD monomer in simulated tumor microenvironment (pH 6.5), owing to the transformation in electrical charge and hydrophobicity/hydrophilicity of this system. The transmission electron microscopy showed that the clustered SA-DOX@HA-CD had a diameter of ~150 nm, and thoroughly disassembled into ~30 nm nanoparticles in response to acidic environment. The disassemble efficiency was approximately 100%. Attributed to this property, SA-DOX@HA-CD led to enhanced cellular internalization and accumulation in 4T1 cells in simulated tumor microenvironment, as well as deep tumor penetration in 3D tumor spheroid model. Besides, the imine bond between DOX and HA-CD endowed DOX with pH-responsive release profile in the acidic lysosome environment. Furthermore, in the orthotopic 4T1 tumor-bearing mouse model, SA-DOX@HA-CD demonstrated higher tumor accumulation than non-aggregated DOX-HA-CD. Meanwhile, in response to the acid tumor microenvironment, the dissociated DOX-HA achieved deep tumor penetration, which consequently resulted in 2.5-fold higher antitumor efficiency. The formulation of self-aggregated SA-DOX@HA-CD provides a simple and effective alternative to prepare pH-responsive size-shrinkable nanodrug delivery systems. Statement of significance The heterogeneity of tumor vasculature and the high tumor interstitial pressure lead to the barriers in tumor accumulation and deep penetration, which calls for opposite properties (e.g. size) of drug delivery systems. To address this dilemma, various size changeable nanoparticles have been developed utilizing special features of tumor microenvironment, such as pH, enzyme and reactive oxygen species. Nevertheless, the current strategies face the problems of incomplete hydrolysis of chemical bonds or insufficient enzyme degradation , which result in only partial size shrinkage, hindering the tumor deep penetration effects. Here we developed a self-assembled nanocluster , which could respond to acidic pH rapidly and thoroughly disassemble into small nanodots due to the alteration of hydrophobicity/hydrophilicity/charge, leading to approximately 100% dissociation. This strategy provides a new concept for design of size changeable drug delivery systems.
研究领域:
药剂学
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肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Danjun WU,Shumin Xu,Xueling Zhang,Yi Li,Wangyang Zhang,Qinying Yan,Qingliang Yang,Fangyuan Guo,Gensheng Yang
The development of smart size-tunable drug delivery nanoplatform enables the solving of the paradox of inconsistent size-dependence of high tumor accumulation and deep penetration during its delivery process, thus achieving superior cancer treatment efficacy. Herein, we report a size-shrinkable nanomicelle complex system with an initial size of 101 nm enabling effective retention around the tumor periphery and could destruct to ultrasmall nanomicelles triggered by a near-infrared (NIR) laser to realize the deep tumor penetration. The nanomicelle system is consisted of an upper critical solution temperature (UCST)-type block copolymer poly(acrylamide-acrylonitrile)-polyethylene glycol-lipoic acid (p(AAm-co-AN)-g-PEG-LA) encapsulating gold nanorods. Upon the irradiation of the NIR laser at the tumor site, gold nanorods could convert the light energy to heat energy, realizing the photothermal ablation of superficial tumor tissue. Concurrently, the large micelles split into a cascade of ultrasmall micelles (∼7 nm), which could easily penetrate into the deep site of the tumor and achieve the in situ “on-demand” release of the loaded drug to exert superior combined photothermal-chemotherapy of cancer. By the precise manipulation of laser, the micelle complex system realized the hierarchical killing from the superficial-to-deep tumor and achieved almost complete tumor growth inhibition on the established xenograft liver tumor mice model.
研究领域:
纳米医学
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肿瘤学
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生物材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2021
·Vol. 17
·期 52
·2104912
·
IF 13.281
Ting Li,Tiantian Chen,Huan Chen,Qi Wang,Zhiyong Liu,Leyi Fang,Mimi Wan,Chun Mao,Jian Shen
Engineered platelets (PLT) can bring new possibilities for diseases treatment due to the specific response for a variety of physiological disease environments. However, the deep penetration of engineered PLT in diseased tissues such as tumor is still an important challenge that restricts the therapeutic effect. Herein, the engineered PLT micromotor (PLT@PDA-DOX) is constructed by a universal self-polymerization modification method of dopamine, and the chemotherapeutic drug doxorubicin (DOX) is loaded by both π–π stacking interaction with polydopamine (PDA) and cellular endocytosis of PLT. The experimental results prove that PLT@PDA-DOX can target to tumor site by the specific binding of PLT with cancer cells, and then the secondary PLT-derived microparticles (PMP@PDA-DOX) are released with the activation of PLT@PDA-DOX by tumor microenvironment (TME). Besides, benefiting from the photothermal conversion capability of PDA, PLT@PDA-DOX micromotors and PMP@PDA-DOX nanomotors are driven by near-infrared light to realize deep penetration. And the PLT-based micro/nanomotors with propulsion capability possess good performance for tumor ablating in vitro and in vivo. In consideration of the operability, mildness, universality of this modification method and the good biocompatibility of PDA, this work may provide a general paradigm for the construction of engineered cells in disease treatment.
研究领域:
生物医学工程
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纳米技术
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癌症研究
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治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Xiaojie Song,Chun-Ling Li,Nan Qiu,Qi-Yan Lv,Xinxin Wu,Hui-Fang Cui
Loading hyaluronidase (Hyal) in a nanocarrier is a potent strategy to degrade the tumor extracellular matrix for tumor deep penetration and enhanced tumor therapy. Herein, a pH-sensitive biomimicking nanosystem with high Hyal loading, effective tumor targeting, and controllable release is constructed. Specifically, cationic mesoporous silica nanoparticles (CMSNs) with large pores 13.52 nm in diameter were synthesized in a one-pot manner by adding N-[3-trimethoxysilylpropyl]-N,N,N-trimethylammonium to a reversed microemulsion reaction system. The Hyal loading rate was as high as 19.47% owing to matched pore size and the cationic surface charge. Subsequently, a pH-sensitive biomimetic hybrid membrane (pHH) composed of pH-sensitive liposome (pHL), red blood cell membrane, and pancreatic cancer cell membrane was camouflaged on the pHL-coated and doxorubicin/Hyal-loaded CMSNs (shortened as DHCM). The DHCM@pHL@pHH is stable at neutral pH while it releases the payloads smoothly in the tumor acidic microenvironment. Consequently, it can escape from macrophage clearance, be specifically taken up by pancreatic cancer cells, and efficiently accumulate at the tumor site. More importantly, it can penetrate deeply in pancreatic tumors with a tumor growth inhibition ratio of 80.46%. The nanosystem is biocompatible and has potential for clinical transformation, and the nanocarrier is promisingly applicable as a platform for encapsulation of various macromolecules for smart and tumor-targeted delivery.
研究领域:
纳米技术
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癌症治疗
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药物递送系统
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science Advances
·
2025
·Vol. 11
·期 36
·
IF 12.5
Fengxiang Liu,Shipeng Ning,Xia Wang,Xiaoyuan Fan,Bin Wan,Fei Sun,Lili Du,Kefan Shi,Xinpeng Zou,Ruihong Zhu,Mingxing Li,Wenwen Shen,Zhonggui He,Kaiyuan Wang,Jin Sun
Cancer stem cells (CSCs) and myeloid-derived suppressor cells (MDSCs) contribute to chemoresistance and immunosuppression, constraining chemoimmunotherapy outcomes. Differentiation therapy, aiming to mature CSCs and MDSCs, shows great promise. However, its efficacy is hindered by limited accessibility in hypoxic deep tumor regions. Inspired by the apoptotic body (ApoBD)–mediated deep tumor penetration, we design a pulsatile sequential drug release system with a core-shell structure. The reversible acid-responsive shell protonates and swells in lysosomes to release doxorubicin, inducing lysosomal escape and cell apoptosis. In ApoBDs, it deprotonates and contracts to prevent excessive drug release. After deep penetration via ApoBDs, the hypoxia-responsive core releases all-trans retinoic acid to reverse CSCs and MDSCs, overcoming chemoresistance and modulating the immuno-microenvironment. This strategy targets the heterogeneous distribution of CSCs and MDSCs in solid tumors, enhancing chemo-intervention and immune checkpoint blockade therapy while presenting encouraging potential for cascade deep tumor penetration and differentiation therapy.
研究领域:
纳米医学
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癌症治疗
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药物递送
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免疫治疗
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生物材料
·
肿瘤微环境
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2020
·
IF 4.902
Yunyan Chen,Mengfei Guo,Ding Qu,Yuping Liu,Jian Guo,Yan Chen
The accumulation and penetration of antitumor drugs in tumor tissues are directly related to their antitumor effects. The particle size of the nanodrug delivery system is one of the most important factors for the accumulation and penetration of antitumor drugs within tumor tissues. Generally, nanodelivery systems of intermediate size (100–120 nm) are capable of efficient accumulation owing to prolonged circulation and enhanced permeability and retention (EPR) effect; however, smaller ones (20–40 nm) are effective for deep penetration within tumor tissue. Currently a conventional drug delivery system cannot possess two types of optimal sizes, simultaneously. To solve this and to enhance cervical cancer treatment, a furin-responsive triterpenine-based liposomal complex (PEGcleavable Tf-CTM/L), with Tf-CTM (transferrin-modified tripterine-loaded coix seed oil microemulsion) in core, coated with a thermo-sensitive lipid and a kind of PEG shell modified with a furin-cleavable peptide was developed to improve tumor-specific accumulation and penetration. Herein, PEGcleavable Tf-CTM/L was capable of efficient accumulation because of EPR effect. The PEG shells could timely detach under stimulation of overexpressed furin protein to solve the problem of the steric hindrance dilemma. The small-sized Tf-CTM released under stimulation of tumor microthermal environment in cervical cancer, which was efficient with regards to deep penetration at tumor sites. Notably, compared to the use of triterpenine alone, PEGcleavable Tf-CTM/L promoted anticervical efficacy and displayed diminished systemic toxicity by efficient accumulation and deep penetration of antitumor drugs within tumor tissues. Our study provides a new strategy, and holds promising potential for anticervical cancer treatment.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
·
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）