BIOMACROMOLECULES
·
2018
·
IF 5.738
Junhua Li,Xuequan Zhang,Mingying Zhao,Lihuang Wu,Kui Luo,Yuji Pu,Bin He
Nanoparticle- and microsphere-based drug delivery systems (DDSs) have attracted wide attention in cancer therapy; those DDSs that are responsive to tumor environment can selectively identify tumor and normal tissues and therefore have shown enhanced anticancer efficacy and alleviated systemic toxicity. Here, tumor-pH-sensitive polymeric microspheres, which are prepared by multiblock poly(l-lactide) with pH-sensitive acetal bonds in the backbone, are employed to efficiently load water-soluble anticancer drug doxorubicin hydrochloride (DOX·HCl, drug loading content: ∼10%). The pH-sensitive DOX-loaded hollow microspheres were in the size range 2–10 μm and exhibited acid-accelerated degradation of polymer matrix and drug release, and thereby efficient in vitro cancer cell inhibition. The microspheres were further intratumorally injected into breast-tumor-bearing mice, and the in vivo anticancer experiment showed that pH-sensitive DOX-loaded microsphere showed better antitumor efficiency and prolonged life-span than its counterpart that does not have pH-responsive property. Moreover, negligible organ toxicity, especially cardiotoxicity that generally exists in DOX-involved chemotherapy where DOX is administrated by intravenous injection, was observed for DOX-loaded microspheres. Hence, tumor-pH-sensitive polymeric microspheres have appeared to be a simple and efficient platform for delivering hydrophilic anticancer drug with excellent anticancer efficacy and low systemic toxicity.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2020
·
IF 3.99
Guoping Li,Mingliang Pei,Peng Liu
Novel tumor nanotheranostics were designed by conjugating doxorubicin (DOX) onto the hydrazine-functionalized crosslinked carbon quantum dots (CQDs)/polyethylene glycol bisacrylate (PEGBA) (C-CQD PEGBA -Hy) nanosponges via an acid-labile imine bond for the tumor intracellular real-time imaging and pH-triggered DOX release. The proposed prodrug nanotheranostics with a DOX content of 14.57 % and a mean hydrodynamic diameter around 116 nm showed excellent pH-triggered drug release performance, with a cumulative release of 52.71 % in the simulated tumor intracellular microenvironment in 4 days, while a premature drug leakage of 7.09 % in the simulated normal physiological medium. Besides, the fluorescence could be recovered during the drug release, indicating the potential application for tumor intracellular real-time imaging.
研究领域:
药学
·
生物医学工程
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF INORGANIC CHEMISTRY
·
2014
·Vol. 2014
·期 36
·6156-6164
·
IF 2.965
Liru Cui,Huiming Lin,Chunyu Yang,Xiao Han,Ting Zhang,Fengyu Qu
Graphical A pH-responsive and magnetic-targeted drug-delivery system was prepared with a Fe 3 O 4 @mesoporous silica core–shell nanostructure as host. Au nanoparticles were used as the capping agent. These were connected to the surface of the mesopore through the hydrazone linkage to restrict the drug release. The system has potential applications in low-pH tissue-targeted therapy. A multifunctional nanocomposite has been successfully prepared for pH-responsive and magnetic-targeting drug delivery. First, Fe 3 O 4 @mesoporous silic (mSiO 2 ) core–shell nanoparticles were synthesized as the nanocapsules. Doxorubicin hydrochloride was adopted as the model drug; after drug loading, gold nanoparticles (5 nm) were connected to block the mesopore through the hydrazone linkage. The hydrazone bond, a typical acid-sensitive bond, could undergo hydrolysis in an acidic environment to induce the release of the capping agent, so that the multifunctional nanocomposite revealed acid-enhanced release performance. What's more, before reaching acid conditions, little premature release was found to take place. Cell experiments were also carried out to reveal the good biocompatibility, fast uptake, and improved toxicity toward HeLa cells. Thus, in association with the magnetic target, the multifunctional nanocomposite shows the potential application for some low-pH tissue-targeted therapy, such as for inflammation and tumors.
研究领域:
纳米医学
·
生物材料学
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
ACS Biomaterials Science & Engineering
·
2023
·
IF 5.8
Siyu Chen,Yicheng Lv,Yue Wang,Deping Kong,Jindong Xia,Jingchao Li,Quan Zhou
Cancer nanomedicine combined with immunotherapy has emerged as a promising strategy for the treatment of cancer. However, precise regulation of the activation of antitumor immunity in targeting tissues for safe and effective cancer immunotherapy remains challenging. Herein, we report a tumor acidic microenvironment-responsive promodulator iron oxide nanoparticle (termed as FGR) with pH-activated action for photothermal-enhanced chemodynamic immunotherapy of cancer. FGR is formed via surface-modifying iron oxide nanoparticles with a dextran-conjugated Toll-like receptor agonist (R848) containing an acid-labile bond. In an acidic tumor microenvironment, the acid-responsive bonds are hydrolyzed to trigger the specific release of R848 to promote the maturation of dendritic cells. In addition, iron oxide nanoparticles within FGR exert photothermal and chemodynamic effects under near-infrared laser irradiation to directly kill tumor cells and induce immunogenic cell death. The synergistic effect of the released immunogenic factors and the acid-activated TLR7/8 pathway stimulates the formation of strong antitumor immunity, resulting in increased infiltration of cytotoxic CD8+ T cells into tumor tissues. As a result, FGR achieves acid-responsive on-demand release and activation of modulators in tumor sites and mediates photothermal-enhanced chemodynamic immunotherapy to inhibit the growth and metastasis of melanoma. Therefore, this work proposes a general strategy for designing prodrug nanomedicines to accurately regulate cancer immunotherapy.
研究领域:
癌症研究
·
纳米技术
·
免疫疗法
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Qingyan Zhang,Pengkai Wu,Jicheng Wu,Hao Shou,Xinliang Ming,Shuqi Wang,Ben Wang
Classical chemotherapeutic drugs may cause immunogenic cell death (ICD), followed by activating CD8+ T cells to promote cell-mediated antitumor immune responses. However, CD8+ T cells become exhausted due to tumor antigens’ continuous stimulation, creating a major obstacle to effectively suppressing tumor growth and metastasis. Here, we develop an approach of chemo-gene combinational nanomedicine to bridge and reprogram chemotherapy and immunotherapy. The dually loaded nanomedicine induces ICD in tumor cells through doxorubicin and reverses the antitumor effects of exhausted CD8+ T cells through the small interfering RNA. The synergistic chemo-gene and fluorine assembly nanomedicine enriched in reactive oxygen species and acid-sensitive bonds results in enhanced cancer immunotherapy to inhibit tumor growth and the lung metastasis of breast cancer in a mouse model of breast cancer and melanoma. This study provides an efficient strategy and insights into chemoimmunological cascade therapy for combating malignant metastatic tumors.
研究领域:
癌症生物学
·
纳米技术
·
免疫治疗
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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