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Min Gao, Xuan Meng, Xuliang Guo, Jundong Zhu, Aiping Fan, Zheng Wang, Yanjun Zhao
Traditional antitumor nanomedicines have been suffering from the poor tumor targeting (ca. 1%) by the enhanced permeability and retention (EPR) effect, and the low drug loading (<5%). It was postulated that engineering all-active nanoplatform could increase the therapeutic efficacy to enable the nanocarrier function as both vehicle and active ingredient. To achieve this, a photosensitizer, Ce6 was encapsulated within polymeric micelles with unsaturated fatty acids as the building blocks. Upon light irradiation, the singlet oxygen produced by Ce6 induced lipid peroxidation, resulting in the generation of both active free radicals and aldehydes...
August 8, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Han Zhang, Kai Liu, Shukun Li, Xia Xin, Shiling Yuan, Guanghui Ma, Xuehai Yan
Minimalist multifunctional platforms for delivering diagnostic and therapeutic agents effectively and safely into tumor sites are highly desired in nanomedicine. Herein, we describe the fabrication of a supramolecular nanoplatform via the amphiphilic amino acid (9-fluorenylmethyloxycarbonyl-L-Leucine, Fmoc-L-L)-modulated self-assembly of a magnetic resonance imaging (MRI) contrast agent (ionic manganese, Mn2+) and photosensitive drug (chlorin e6, Ce6). Coordination drives the coassembly of Fmoc-L-L and Mn2+ to generate a nanoscale supramolecular network to adaptively encapsulate Ce6...
August 9, 2018: ACS Nano
Binghua Wang, Jingyi An, Huifang Zhang, Shudong Zhang, Huijuan Zhang, Lei Wang, Hongling Zhang, Zhenzhong Zhang
While immunotherapy has a tremendous clinical potential to combat cancer, immune responses generated by conventional cancer immunotherapy remain not enough to completely eliminate tumors, mainly due to the tumor's immunosuppressive microenvironment and heterogeneity of tumor immunogenicity. To improve antitumor immune responses and realize personalized immunotherapy, in this report, endogenous tumor antigens (ETAs) that dynamically present on tumor cells are transported to lymph nodes (LNs). Based on the hypothesis that nano Fe3 O4 (≈10 nm) could serve as the nanocarrier for transporting ETAs from the tumor to LNs, we wondrously find that Fe3 O4 has a tremendous potential to improve cancer immunotherapy, because of its excellent protein-captured efficiency and LNs-targeted ability...
August 6, 2018: Small
Xinyi Lin, Ming Wu, Ming Li, Zhixiong Cai, Haiyan Sun, Xionghong Tan, Jiong Li, Yongyi Zeng, Xiaolong Liu, Jingfeng Liu
The development of multifunctional carriers incorporating genetic and photodynamic therapy (PDT) for synergistic antitumor treatment has attracted intensive interests very recently. However, most of the currently reported systems employ passive gene release strategies depending on tumor microenvironment, which are negatively affected by the heterogeneity of cancer cells, thus resulting in limited controllability in therapeutic progress. Herein, a novel photo-responsive hollow silica nanoparticle (HNP)-based gene and photosensitizer (PS) co-delivery nanovehicle is designed for dual-wavelength light-triggered synergistic gene and PDT therapy...
August 2018: Acta Biomaterialia
Chuang Liu, Lijia Luo, Leyong Zeng, Jie Xing, Yuanzhi Xia, Shan Sun, Luyun Zhang, Zhe Yu, Junlie Yao, Zhangsen Yu, Ozioma Udochukwu Akakuru, Madiha Saeed, Aiguo Wu
AuroShell nanoparticles (sealed gold nanoshell on silica) are the only inorganic materials that are approved for clinical trial for photothermal ablation of solid tumors. Based on that, porous gold nanoshell structures are thus critical for cancer multiple theranostics in the future owing to their inherent cargo-loading ability. Nevertheless, adjusting the diverse experimental parameters of the reported procedures to obtain porous gold nanoshell structures is challenging. Herein, a series of amino-functionalized porous metal-organic frameworks (NH2 -MOFs) nanoparticles are uncovered as superior templates for porous gold nanoshell deposition (NH2 -MOFs@Aushell ) by means of a more facile and general one-step method, which combines the enriched functionalities of NH2 -MOFs with those of porous gold nanoshells...
July 29, 2018: Small
Yayun Wang, Makiko Sakka, Haruka Yagi, Satoshi Kaneko, Hirotaka Katsuzaki, Emi Kunitake, Tetsuya Kimura, Kazuo Sakka
Ruminiclostridium josui Abf62A-Axe6A is a modular enzyme comprising (in order from the N-terminus): an N-terminal signal peptide, a glycoside hydrolase family 62 (GH62) catalytic module, a family 6 carbohydrate binding module (CBM6), a dockerin module and an additional carbohydrate esterase family 6 catalytic module (CE6). In this study, three Abf62A-Axe6A derivatives were constructed, overexpressed in Escherichia coli, purified, and biochemically characterized: RjAbf62A-Axe6A, containing all four modules but lacking the signal peptide; RjAbf62A-CBM6, containing the GH62 and CBM6 modules; and RjAxe6A, containing only CE6...
October 2018: Enzyme and Microbial Technology
Zhenyu Luo, Hao Tian, Lanlan Liu, Zhikuan Chen, Ruijing Liang, Ze Chen, Zhihao Wu, Aiqing Ma, Mingbin Zheng, Lintao Cai
Hypoxia is a characteristic feature of solid tumors and an important causation of resistance to chemotherapy and photodynamic therapy (PDT). It is challenging to develop efficient functional nanomaterials for tumor oxygenation and therapeutic applications. Methods: Through disulfide reconfiguration to hybridize hemoglobin and albumin, tumor-targeted hybrid protein oxygen carriers (HPOCs) were fabricated, serving as nanomedicines for precise tumor oxygenation and simultaneous enhancement of hypoxia-dampened chemotherapy and photodynamic therapy...
2018: Theranostics
Pham Thi Thu Phuong, Sungin Lee, Changkyu Lee, Bohyung Seo, Sanghyun Park, Kyung Taek Oh, Eun Seong Lee, Han-Gon Choi, Beom Soo Shin, Yu Seok Youn
Chlorin e6 (Ce6) has attracted considerable interest as a promising second-generation photosensitizer for photodynamic therapy (PDT). However, the in vivo availability of Ce6 is significantly restricted by its low water solubility and poor ability to target tumors. We sought to overcome the limitations of Ce6 by using albumin nanoparticles with nab™ (nanoparticle albumin-bound) technology. The fabricated albumin nanoparticles consisted of bovine serum albumin (BSA), Ce6-BSA, and beta-carotene as a carrier, photosensitizing agent, and cross-linker, respectively...
July 10, 2018: Colloids and Surfaces. B, Biointerfaces
Siyu Wang, Fang Guo, Yanhui Ji, Meng Yu, Jinping Wang, Nan Li
Photodynamic therapy (PDT) is commonly restricted by inefficient tumor selectivity during clinical study. Hence, a mitochondria-targeting multifunctional nanocarrier "theranosome (TNS)" was developed for near-infrared fluorescent (NIRF) imaging and photoacoustic (PA) imaging. What's more, the TNS can also enhance PDT efficacy. In this work, chlorin e6 (Ce6) undertakes reactive oxygen generation and fluorescence emission. Ce6 was quenched when being encapsulated into TNS together with IR780 iodide...
August 6, 2018: Molecular Pharmaceutics
Mijin Koo, Kyung Taek Oh, Gwangjin Noh, Eun Seong Lee
We report functional gold nanoparticles (AuNPs) with a pH-sensitive γ-cyclodextrin (CD) cap. These particles include two chargeable CD molecules on their surface. CD with dopamine and amine (NH2 ) groups (hereafter termed as dCD-NH2 ) was anchored to the gold surface and then electrostatically complexed with the CD with 2,3-dimethylmaleic acid (DMA) and chlorin e6 (Ce6) (hereafter termed as cCD-DMA), producing an ionic complex consisting of dCD-NH2 and cCD-DMA. Under the acidic environment (pH 6.8) existing in most solid tumors, the ionic complex was destabilized because of the decoupling of DMA, resulting in the release of cCD (without DMA) from the AuNPs, resulting in extensive tumoral uptake of AuNPs with dCD-NH2 (because of their electrostatic attraction to tumor cells)...
July 25, 2018: ACS Applied Materials & Interfaces
Yang Luo, Wei Zhang, Zhengfang Liao, Shengnan Yang, Shengtao Yang, Xinhua Li, Fang Zuo, Jianbin Luo
Core-shell (C/S) structured upconversion coated Fe₃O₄ nanoparticles (NPs) are of great interest due to their potential as magnetic resonance imaging (MRI) and upconversion luminescent (UCL) imaging agents, as well as near-infrared activated photodynamic therapy (PDT) platforms. When C/S structured Fe₃O₄@Mn2+ -doped NaYF₄:Yb/Er NPs were prepared previously, well-defined C/S-NPs could not be formed without the doping of Mn2+ during synthesis. Here, the role of Mn2+ doping on the synthesis of core-shell structured magnetic-upconversion nanoparticles (MUCNPs) is investigated in detail...
June 26, 2018: Nanomaterials
Shubhajit Paul, Paul Wan Sia Heng, Lai Wah Chan
OBJECTIVES: Chlorin e6 is a poorly water-soluble photoactive drug. Its monomers form aggregates at the tumour physiological pH, which drastically reduces its photodynamic efficacy. This study aimed to improve the dissolution rate and photodynamic efficacy of chlorin e6 by nanosuspension formulation using biodegradable sucrose esters as drug carrier. METHODS: A modified emulsion-solvent diffusion method was used to prepare the nanosuspension, where amount of Ce6, ratio of sucrose monopalmitate to sucrose monolaurate as carrier and ratio of dichloromethane to acetone as solvent, were varied using central composite design...
June 25, 2018: Journal of Pharmacy and Pharmacology
Hao-Ran Jia, Ya-Xuan Zhu, Ke-Fei Xu, Fu-Gen Wu
Melittin (MEL) is recognized as a highly potent therapeutic peptide for treating various human diseases including cancer. However, the clinical applications of MEL are largely restricted by its severe hemolytic activity and nonspecific cytotoxicity. Here, it is found that MEL can form a stable supramolecular nanocomplex of ≈60 nm with the photosensitizer chlorin e6 (Ce6), which after hyaluronic acid (HA) coating can achieve robust, safe, and imaging-guided tumor ablation. The as-designed nanocomplex (denoted as MEL/Ce6@HA) shows largely reduced hemolysis and selective cytolytic activity toward cancer cells...
June 21, 2018: Advanced Healthcare Materials
So-Ri Lee, Young-Jin Kim
In photodynamic therapy (PDT), chlorin e6 (Ce6), with its high phototoxic potential and strong absorption of visible light, penetrates deeply into photodamaged tissue. However, despite this fact, the direct application of Ce6 to PDT has been limited by its low water solubility and poor cancer cell localization. To ameliorate this situation, we report herein on the use of a hydrophilic nanoconjugate (DC) comprised of Ce6 and poly(amidoamine) dendrimer, which improves the water solubility and intracellular uptake of Ce6, thereby enhancing PDT efficacy...
June 18, 2018: Nanomaterials
Feng Li, Chao Chen, Xixi Yang, Xinyu He, Zhangyan Zhao, Jie Li, Yue Yu, Xianzhu Yang, Jun Wang
Nanocarrier-mediated photodynamic therapy (PDT), which involves the systemic delivery of photosensitizers (PSs) into tumor tissue and tumor cells, has emerged as an attractive treatment for cancer. However, insufficient PS release limits intracellular cytotoxic reactive oxygen species (ROS) generation, which has become a major obstacle to improving the PDT therapeutic efficacy. Herein, a novel hyperbranched polyphosphoester (hbPPE) containing numerous acetal bonds (S-hbPPE/Ce6) was explored as a chlorin e6 (Ce6) nanocarrier for PDT...
June 27, 2018: ACS Applied Materials & Interfaces
Chun-Yang Sun, Ziyang Cao, Xue-Jun Zhang, Rong Sun, Chun-Shui Yu, Xianzhu Yang
The simple integration of chemotherapeutic drugs and photosensitizers (PSs) into the same nanocarriers only achieves a combination of chemo-photodynamic therapy but may not confer synergistic effects. The boosted intracellular release of chemotherapeutic drugs during the photodynamic therapy (PDT) process is necessary to achieve a cascade of amplified synergistic therapeutic effects of chemo-photodynamic therapy. Methods: In this study, we explored an innovative hyperbranched polyphosphate (RHPPE) containing a singlet oxygen (SO)-labile crosslinker to boost drug release during the PDT process...
2018: Theranostics
Xiaolong Zhang, Ming Wu, Jiong Li, Shanyou Lan, Yongyi Zeng, Xiaolong Liu, Jingfeng Liu
The tumor hypoxic environment as well as photodynamic therapy (PDT)-induced hypoxia could severely limit the therapeutic efficacy of traditional PDT. Fortunately, the smart integration of hypoxia-responsive drug delivery system with PDT might be a promising strategy to enhance the PDT efficiency that is hindered by the hypoxic environment. Herein, a novel azobenzene (AZO) containing conjugated polymers (CPs)-based nanocarriers (CPs-CPT-Ce6 NPs) was constructed for the combination of PDT with chemotherapy, as well as to enhance the hypoxia-responsive drug release by light...
July 5, 2018: ACS Applied Materials & Interfaces
Zhen Lu Yang, Wei Tian, Qing Wang, Ying Zhao, Yun Lei Zhang, Ying Tian, Yu Xia Tang, Shou Ju Wang, Ying Liu, Qian Qian Ni, Guang Ming Lu, Zhao Gang Teng, Long Jiang Zhang
Oxygen (O2 ) plays a critical role during photodynamic therapy (PDT), however, hypoxia is quite common in most solid tumors, which limits the PDT efficacy and promotes the tumor aggression. Here, a safe and multifunctional oxygen-evolving nanoplatform is costructured to overcome this problem. It is composed of a prussian blue (PB) core and chlorin e6 (Ce6) anchored periodic mesoporous organosilica (PMO) shell (denoted as PB@PMO-Ce6). In the highly integrated nanoplatform, the PB with catalase-like activity can catalyze hydrogen peroxide to generate O2 , and the Ce6 transform the O2 to generate more reactive oxygen species (ROS) upon laser irradiation for PDT...
May 2018: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
Barbara Poinard, Samuel Zhan Yuan Neo, Eugenia Li Ling Yeo, Howard Peng Sin Heng, Koon Gee Neoh, James Chen Yong Kah
Our study shows a facile two-step method which does not require the use of core templates to load a hydrophobic photosensitizer drug chlorin e6 (Ce6) within polydopamine (PDA) nanoparticles (NPs) while maintaining the intrinsic surface properties of PDA NPs. This structure is significantly different from hollow nanocapsules which are less stiff as they do not possess a core. To our knowledge, there exist no similar studies in the literature on drug loading within the polymer matrix of PDA NPs. We characterized the drug loading and release behavior of the photosensitizer Ce6 and demonstrated the therapeutic efficacy of the combined photodynamic (PDT) and photothermal therapy (PTT) from Ce6 and PDA, respectively, under a single wavelength of 665 nm irradiation on bladder cancer cells...
June 27, 2018: ACS Applied Materials & Interfaces
Da Hye Kim, Hee Sook Hwang, Kun Na
A combination of chemo-photodynamic therapy has been manifested as a promising strategy for efficient cancer treatment due to the enhanced therapeutic efficacy. Here, we designed doxorubicin (DOX)-loaded photoresponsive micelles (DPRMs) based on a combination of chlorin e6 (Ce6) and lipoic acid (LA) conjugated methoxy-poly(ethylene) glycol (mPEG-Ce6, mPEG-LA) to achieve effective drug delivery using a single system. DPRMs were optimized with different molar ratios of mPEG-Ce6 and mPEG-LA which showed uniformly spherical morphology of size ∼130 nm and approximately 9% of DOX loading contents...
July 6, 2018: Biomacromolecules
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