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Yao‐Xin Lin Yi Wang Sheng‐Lin Qiao Hong‐Wei An Ruo‐Xin Zhang Zeng‐Ying Qiao R. P. Y. J. Rajapaksha Lei Wang Hao Wang 《Small (Weinheim an der Bergstrasse, Germany)》2016,12(21):2921-2931
In drug delivery systems, pH‐sensitive polymers are commonly used as drug carriers, and significant efforts have been devoted to the aspects of controlled delivery and release of drugs. However, few studies address the possible autophagic effects on cells. Here, for the first time, using a fluorescent autophagy‐reporting cell line, this study evaluates the autophagy‐induced capabilities of four types of pH‐sensitive polymeric nanoparticles (NPs) with different physical properties, including size, surface modification, and pH‐sensitivity. Based on experimental results, this study concludes that pH‐sensitivity is one of the most important factors in autophagy induction. In addition, this study finds that variation of concentration of NPs could cause different autophagic effect, i.e., low concentration of NPs induces autophagy in an mTOR‐dependent manner, but high dose of NPs leads to autophagic cell death. Identification of this tunable autophagic effect offers a novel strategy for enhancing therapeutic effect in cancer therapy through modulation of autophagy. 相似文献
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Baoji Du Li Tian Xiaoxiao Gu Dan Li Erkang Wang Jin Wang 《Small (Weinheim an der Bergstrasse, Germany)》2015,11(19):2333-2340
Gene therapy is a potential method for treating a large range of diseases. Gene vectors are widely used in gene therapy for promoting the gene delivery efficiency to the target cells. Here, gold nanoparticles (AuNPs) coated with dimethyldioctadecylammonium bromide (DODAB)/dioleoylphosphatidylethanolamine (DOPE) are synthesized using a facile method for a new gene vector (DODAB/DOPE‐AuNPs), which possess 3‐ and 1.5‐fold higher transfection efficiency than those of DODAB‐AuNPs and a commercial transfection agent, respectively. Meanwhile, it is nontoxic with concentrations required for effective gene delivery. Imaging and quantification studies of cellular uptake reveal that DOPE increases gene copies in cells, which may be attributed to the smaller size of AuNPs/DNA complexes. The dissociation efficiency of DNA from the endocytic pathway is quantified by incubating with different buffers and investigated directly in the cells. The results suggest that DOPE increases the internalization of AuNPs/DNA complexes and promotes DNA release from early endosomes for the vector is sensitive to the anionic lipid membrane and the decreasing pH along the endocytic pathway. The new vector contains the potential to be the new alternative as gene delivery vector for biomedical applications. 相似文献
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Xing Guo Xiao Wei Yuting Jing Shaobing Zhou 《Advanced materials (Deerfield Beach, Fla.)》2015,27(41):6450-6456
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Zhihong Zhang Juan Chen Lili Ding Honglin Jin Jonathan F. Lovell Ian R. Corbin Weiguo Cao Pui‐Chi Lo Mi Yang Ming‐Sound Tsao Qingming Luo Gang Zheng 《Small (Weinheim an der Bergstrasse, Germany)》2010,6(3):430-437
Targeted delivery of intracellularly active diagnostics and therapeutics in vivo is a major challenge in cancer nanomedicine. A nanocarrier should possess long circulation time yet be small and stable enough to freely navigate through interstitial space to deliver its cargo to targeted cells. Herein, it is shown that by adding targeting ligands to nanoparticles that mimic high‐density lipoprotein (HDL), tumor‐targeted sub‐30‐nm peptide–lipid nanocarriers are created with controllable size, cargo loading, and shielding properties. The size of the nanocarrier is tunable between 10 and 30 nm, which correlates with a payload of 15–100 molecules of fluorescent dye. Ligand‐directed nanocarriers targeting epidermal growth factor receptor (EGFR) are confirmed both in vitro and in vivo. The nanocarriers show favorable circulation time, tumor accumulation, and biodistribution with or without the targeting ligand. The EGFR targeting ligand is proved to be essential for the EGFR‐mediated tumor cell uptake of the nanocarriers, a prerequisite of intracellular delivery. The results demonstrate that targeted HDL‐mimetic nanocarriers are useful delivery vehicles that could open new avenues for the development of clinically viable targeted nanomedicine. 相似文献
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Chi Yao Wenxing Wang Peiyuan Wang Mengyao Zhao Xiaomin Li Fan Zhang 《Advanced materials (Deerfield Beach, Fla.)》2018,30(7)
Tumor hypoxia is typically presented in the central region of solid tumors, which is mainly caused by an inadequate blood flow and oxygen supply. In the conventional treatment of hypoxic human tumors, not only the oxygen‐dependent photodynamic therapy (PDT), but also antitumor drug‐based chemotherapy, is considerably limited. The use of direct oxygen delivering approach with oxygen‐dependent PDT or chemotherapy may potentiate the reactive oxygen species (ROS)‐mediated cytotoxicity of the drug toward normal tissues. Herein, a synergetic one‐for‐all mesoporous cerium oxide upconversion biophotocatalyst is developed to achieve intratumorally endogenous H2O2‐responsive self‐sufficiency of O2 and near‐infrared light controlled PDT simultaneously for overcoming hypoxia cancer. Furthermore, the sufficient O2 plays an important role in overcoming the chemotherapeutic drug‐resistant cancer caused by hypoxia, therefore inducing tumor cell apoptosis significantly. 相似文献
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Hao L Patel PC Alhasan AH Giljohann DA Mirkin CA 《Small (Weinheim an der Bergstrasse, Germany)》2011,7(22):3158-3162
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Ali H. Alhasan Pinal C. Patel Chung Hang J. Choi Chad A. Mirkin 《Small (Weinheim an der Bergstrasse, Germany)》2014,10(1):186-192
Exosomes are a class of naturally occurring nanomaterials that play crucial roles in the protection and transport of endogenous macromolecules, such as microRNA and mRNA, over long distances. Intense effort is underway to exploit the use of exosomes to deliver synthetic therapeutics. Herein, transmission electron microscopy is used to show that when spherical nucleic acid (SNA) constructs are endocytosed into PC‐3 prostate cancer cells, a small fraction of them (<1%) can be naturally sorted into exosomes. The exosome‐encased SNAs are secreted into the extracellular environment from which they can be isolated and selectively re‐introduced into the cell type from which they were derived. In the context of anti‐miR21 experiments, the exosome‐encased SNAs knockdown miR‐21 target by approximately 50%. Similar knockdown of miR‐21 by free SNAs requires a ≈3000‐fold higher concentration. 相似文献
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Zhenwei Su Zecong Xiao Yong Wang Jinsheng Huang Yongcheng An Xu Wang Xintao Shuai 《Small (Weinheim an der Bergstrasse, Germany)》2020,16(7)
Immune checkpoint blockade (ICB) is demonstrating great potential in cancer immunotherapy nowadays. Yet, the low response rate to ICB remains an urgent challenge for tumor immunotherapy. A pH and matrix metalloproteinase dual‐sensitive micellar nanocarrier showing spatio‐temporally controlled release of anti‐PD‐1 antibody (aPD‐1) and paclitaxel (PTX) in solid tumors is prepared to realize synergistic cancer chemoimmunotherapy. Antitumor immunity can be activated by PTX‐induced immunogenic cell death (ICD), while aPD‐1 blocks the PD‐1/PD‐L1 axis to suppress the immune escape due to PTX‐induced PD‐L1 up‐regulation, thus resulting in a synergistic antitumor chemoimmunotherapy. Through decoration with a sheddable polyethylene glycol (PEG) shell, the nanodrug may better accumulate in tumors to boost the synergistic antitumor treatment in a mouse melanoma model. The present study demonstrates a potent antitumor chemoimmunotherapy utilizing tumor microenvironment‐sensitive micelles bearing a sheddable PEG layer to mediate site‐specific sequential release of aPD‐1 and PTX. 相似文献
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Hai Wang Yan Wu Ruifang Zhao Guangjun Nie 《Advanced materials (Deerfield Beach, Fla.)》2013,25(11):1616-1622
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Tianjiao Ji Ying Zhao Yanping Ding Guangjun Nie 《Advanced materials (Deerfield Beach, Fla.)》2013,25(26):3508-3525
Malignant tumors remain a major health burden throughout the world and effective therapeutic strategies are urgently needed. Cancer nanotechnology, as an integrated platform, has the potential to dramatically improve cancer diagnosis, imaging, and therapy, while reducing the toxicity associated with the current approaches. Tumor microenvironment is an ensemble performance of various stromal cells and extracellular matrix. The recent progress in understanding the critical roles and the underlying mechanisms of the tumor microenvironment on tumor progression has resulted in emerging diagnostic and therapeutic nanomaterials designed and engineered specifically targeting the microenvironment components. Meanwhile, the bio‐physicochemical differences between tumor and normal tissues have recently been exploited to achieve specific tumor‐targeting for cancer diagnosis and treatment. Here, the major players in the tumor microenvironment and their biochemical properties, which can be utilized for the design of multifunctional nanomaterials with the potential to target and regulate this niche, are summarized. The recent progress in engineering intelligent and versatile nanomaterials for targeting and regulating the tumor microenvironment is emphasized. Although further investigations are required to develop robust methods for more specific tumor‐targeting and well‐controlled nanomaterials, the applications of tumor microenvironment regulation‐based nanotechnology for safer and more effective anticancer nanomedicines have been proven successful and will eventually revolutionize the current landscape of cancer therapy. 相似文献
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Lingzhi Zhao Wei Yuan Huijun Phoebe Tham Hongzhong Chen Pengyao Xing Huijing Xiang Xin Yao Xiaochen Qiu Yu Dai Liangliang Zhu Fuyou Li Yanli Zhao 《Small (Weinheim an der Bergstrasse, Germany)》2017,13(29)
Inhomogeneous heating by photothermal therapy (PTT) during cancer treatment often results in the recurrence of tumors. Thus, integrating PTT with chemotherapy (CHT) may provide a complementary treatment for enhanced therapeutic efficiency. Herein, this study develops a hollow structured polymer–silica nanohybrid (HPSN) as a nanocarrier to simultaneously deliver the anticancer drug paclitaxel and photothermal agent palladium phthalocyanine to tumors through enhanced permeation and the retention effect. A combinational CHT/PTT therapy on mice bearing aggressive tumor grafts is conducted. The highly malignant tumor model, which recurs after sole treatment of PTT, can be eradicated by the combined CHT/PTT treatment. In addition, most of the off‐targeted HPSN nanocarriers can be excreted through a hepatobiliary pathway in about 10 d. Serology results show that the fast‐clearable HPSN can significantly reduce the side effect of the loaded paclitaxel drug. The present work provides an alternative approach for combinational cancer treatment with high therapeutic efficiency. 相似文献
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Ranran Guo Haibao Peng Ye Tian Shun Shen Wuli Yang 《Small (Weinheim an der Bergstrasse, Germany)》2016,12(33):4541-4552
Photothermal therapy (PTT) and photodynamic therapy (PDT) are promising cancer treatment modalities in current days while the high laser power density demand and low tumor accumulation are key obstacles that have greatly restricted their development. Here, magnetic composite nanoparticles for dual‐modal PTT and PDT which have realized enhanced cancer therapeutic effect by mitochondria‐targeting are reported. Integrating PTT agent and photosensitizer together, the composite nanoparticles are able to generate heat and reactive oxygen species (ROS) simultaneously upon near infrared (NIR) laser irradiation. After surface modification of targeting ligands, the composite nanoparticles can be selectively delivered to the mitochondria, which amplify the cancer cell apoptosis induced by hyperthermia and the cytotoxic ROS. In this way, better photo therapeutic effects and much higher cytotoxicity are achieved by utilizing the composite nanoparticles than that treated with the same nanoparticles missing mitochondrial targeting unit at a low laser power density. Guided by NIR fluorescence imaging and magnetic resonance imaging, then these results are confirmed in a humanized orthotropic lung cancer model. The composite nanoparticles demonstrate high tumor accumulation and excellent tumor regression with minimal side effect upon NIR laser exposure. Therefore, the mitochondria‐targeting composite nanoparticles are expected to be an effective phototherapeutic platform in oncotherapy. 相似文献
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Peng Mi Horacio Cabral Kazunori Kataoka 《Advanced materials (Deerfield Beach, Fla.)》2020,32(13):1902604
Development of drug-delivery systems that selectively target neoplastic cells has been a major goal of nanomedicine. One major strategy for achieving this milestone is to install ligands on the surface of nanocarriers to enhance delivery to target tissues, as well as to enhance internalization of nanocarriers by target cells, which improves accuracy, efficacy, and ultimately enhances patient outcomes. Herein, recent advances regarding the development of ligand-installed nanocarriers are introduced and the effect of their design on biological performance is discussed. Besides academic achievements, progress on ligand-installed nanocarriers in clinical trials is presented, along with the challenges faced by these formulations. Lastly, the future perspectives of ligand-installed nanocarriers are discussed, with particular emphasis on their potential for emerging precision therapies. 相似文献
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Ge Gao Yao‐Wen Jiang Wei Sun Yuxin Guo Hao‐Ran Jia Xin‐Wang Yu Guang‐Yu Pan Fu‐Gen Wu 《Small (Weinheim an der Bergstrasse, Germany)》2019,15(33)
Photothermal therapy (PTT) usually requires hyperthermia >50 °C for effective tumor ablation, which inevitably induces heating damage to the surrounding normal tissues/organs. Moreover, low tumor retention and high liver accumulation are the two main obstacles that significantly limit the efficacy and safety of many nanomedicines. To solve these problems, a smart albumin‐based tumor microenvironment‐responsive nanoagent is designed via the self‐assembly of human serum albumin (HSA), dc‐IR825 (a cyanine dye and a photothermal agent), and gambogic acid (GA, a heat shock protein 90 (HSP90) inhibitor and an anticancer agent) to realize molecular targeting‐mediated mild‐temperature PTT. The formed HSA/dc‐IR825/GA nanoparticles (NPs) can escape from mitochondria to the cytosol through mitochondrial disruption under near‐infrared (NIR) laser irradiation. Moreover, the GA molecules block the hyperthermia‐induced overexpression of HSP90, achieving the reduced thermoresistance of tumor cells and effective PTT at a mild temperature (<45 °C). Furthermore, HSA/dc‐IR825/GA NPs show pH‐responsive charge reversal, effective tumor accumulation, and negligible liver deposition, ultimately facilitating synergistic mild‐temperature PTT and chemotherapy. Taken together, the NIR‐activated NPs allow the release of molecular drugs more precisely, ablate tumors more effectively, and inhibit cancer metastasis more persistently, which will advance the development of novel mild‐temperature PTT‐based combination strategies. 相似文献
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Caina Xu Ping Wang Jingpeng Zhang Huayu Tian Kinam Park Xuesi Chen 《Small (Weinheim an der Bergstrasse, Germany)》2015,11(34):4321-4333
A pulmonary codelivery system that can simultaneously deliver doxorubicin (DOX) and Bcl2 siRNA to the lungs provides a promising local treatment strategy for lung cancers. In this study, DOX is conjugated onto polyethylenimine (PEI) by using cis‐aconitic anhydride (CA, a pH‐sensitive linker) to obtain PEI‐CA‐DOX conjugates. The PEI‐CA‐DOX/siRNA complex nanoparticles are formed spontaneously via electrostatic interaction between cationic PEI‐CA‐DOX and anionic siRNA. The drug release experiment shows that DOX releases faster at acidic pH than at pH 7.4. Moreover, PEI‐CA‐DOX/Bcl2 siRNA complex nanoparticles show higher cytotoxicity and apoptosis induction in B16F10 cells than those treated with either DOX or Bcl2 siRNA alone. When the codelivery systems are directly sprayed into the lungs of B16F10 melanoma‐bearing mice, the PEI‐CA‐DOX/Bcl2 siRNA complex nanoparticles exhibit enhanced antitumor efficacy compared with the single delivery of DOX or Bcl2 siRNA. Compared with systemic delivery, most drug and siRNA show a long‐term retention in the lungs via pulmonary delivery, and a considerable number of the drug and siRNA accumulate in tumor tissues of lungs, but rarely in normal lung tissues. The PEI‐CA‐DOX/Bcl2 siRNA complex nanoparticles are promising for the treatment of metastatic lung cancer by pulmonary delivery with low side effects on the normal tissues. 相似文献
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