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Ph in cancer therapy

Xianwen Wang, Fei Li, Xu Yan, Yan Ma, Zhaohua Miao, Liang Dong, Huajian Chen, Yang Lu, Zhengbao Zha
Big size induced long-term retention in the body has hampered the translational applications of many reported nanomedicine. Herein, we reported a multifunctional theranostic agent composed of ultrasmall polyacrylic acid functionalized Ni0.85Se nanoparticles (PAA-Ni0.85Se NPs), which were successfully obtained through a facile ambient aqueous precipitation strategy. Without exhibiting any noticeable toxicity, the as-prepared PAA-Ni0.85Se NPs (average diameter of 6.40 ± 1.89 nm) showed a considerable absorption in near-infrared (NIR) region and high photothermal conversion efficiency (PTCE) of 54...
November 17, 2017: ACS Applied Materials & Interfaces
Qianhua Feng, Wanxia Zhang, Xuemei Yang, Yuzhen Li, Yongwei Hao, Hongling Zhang, Lin Hou, Zhenzhong Zhang
Herein, a pH/ultrasound dual-responsive gas generator is reported, which is based on mesoporous calcium carbonate (MCC) nanoparticles by loading sonosensitizer (hematoporphyrin monomethyl ether (HMME)) and modifying surface hyaluronic acid (HA). After pinpointing tumor regions with prominent targeting efficiency, HMME/MCC-HA decomposes instantaneously under the cotriggering of tumoral inherent acidic condition and ultrasound (US) irradiation, concurrently accompanying with CO2 generation and HMME release with spatial/temporal resolution...
November 15, 2017: Advanced Healthcare Materials
Ananda Chowdhury, Robert G Brinson, Beiyang Wei, William G Stetler-Stevenson
Tissue Inhibitor of Metalloprotease -2 (TIMP-2) is a secreted 21 kDa multifunctional protein first described as an endogenous inhibitor of matrix metalloproteinases (MMPs) that prevents breakdown of the extracellular matrix often observed in chronic diseases. TIMP-2 diminishes growth factor-mediated cell proliferation in vitro, as well as neoangiogenesis and tumor growth in vivo independent of its MMP-inhibitory activity, . These physiological properties make TIMP-2 an excellent candidate for further pre-clinical development as a biologic therapy of cancer...
November 15, 2017: Biochemistry
Pham Van Quyet, Bernice Mei Jin Tan, Celine Valeria Liew, Lai Wah Chan, Quan Sing Ng, Paul Wan Sia Heng
L-N(G)-nitroarginine (LNNA), an analogue of L-arginine, is a competitive inhibitor of nitric oxide synthase which causes the selective reduction of blood flow to tumor cells. Despite the potential of LNNA to function as an adjuvant in cancer therapies, its poor solubility and stability have hindered the development of an injectable formulation of LNNA that is suitable for human administration. This work, for the first time, details a systematic study on the determination of equilibrium Ka constants and the rate law of LNNA degradation...
November 15, 2017: Drug Development and Industrial Pharmacy
Yi Teng Fong, Chih-Hao Chen, Jyh-Ping Chen
By taking advantage of the pH-sensitive drug release property of graphene oxide (GO) after intracellular uptake, we prepared folic acid (FA)-conjugated GO (GOFA) for targeted delivery of the chemotherapeutic drug doxorubicin (DOX). GOFA-DOX was further encapsulated in an injectable in-situ forming thermo-sensitive hyaluronic acid-chitosan-g-poly(N-isopropylacrylamide) (HACPN) hydrogel for intratumoral delivery of DOX. As the degradation time of HACPN could be extended up to 3 weeks, intratumoral delivery of GOFA-DOX/HACPN could provide controlled and targeted delivery of DOX through slow degradation HACPN and subsequent cellular uptake of released GOFA-DOX by tumor cells through interactions of GOFA with folate receptors on the tumor cell's surface...
November 14, 2017: Nanomaterials
Yanan Tan, Yun Zhu, Yue Zhao, Lijuan Wen, Tingting Meng, Xuan Liu, Xiqin Yang, Suhuan Dai, Hong Yuan, Fuqiang Hu
Mitochondria, crucial regulators of inducing tumor cells apoptosis, can be treated as the prime target for tumor therapy. The selective and responsive release of proapoptotic therapeutics into mitochondria may notably improve antitumor efficiency. Herein, (4-Carboxybutyl) triphenylphosphonium bromide (CTPP), a lipophilic cation, was conjugated with glucolipid-like conjugates (CSOSA) to produce mitochondria-targeted conjugates (CTPP-CSOSA). Loading with weakly acidic drug Celastrol (Cela), CTPP-CSOSA/Cela micelles could selectively respond to mitochondrial alkaline pH (pH 8...
July 31, 2017: Biomaterials
Marina Martínez-Carmona, Daniel Lozano, Montserrat Colilla, María Vallet-Regí
A novel multifunctional nanodevice based in doxorubicin (DOX)-loaded mesoporous silica nanoparticles (MSNs) as nanoplatforms for the assembly of different building blocks has been developed for bone cancer treatment. These building blocks consists of: i) a polyacrylic acid (PAA) capping layer grafted to MSNs via an acid-cleavable acetal linker, to minimize premature cargo release and provide the nanosystem of pH-responsive drug delivery ability; and ii) a targeting ligand, the plant lectin concanavalin A (ConA), able to selectively recognize, bind and internalize owing to certain cell-surface glycans, such as sialic acids (SA), overexpressed in given tumor cells...
November 7, 2017: Acta Biomaterialia
Tingsheng Yan, Jinju Cheng, Zongjun Liu, Feng Cheng, Xinjing Wei, Jinmei He
In order to optimize the chemotherapeutic efficacy of doxorubicin (DOX) and improve the photodynamic therapeutic effectiveness of rose bengal (RB), a mesoporous silica nanoparticle system was designed as the carrier of RB and DOX for chemo-photodynamic combination therapy. A pH-sensitive strategy has been exploited to enhance the delivery efficiency. Our results suggested that the production of singlet oxygen was independent of the release of RB while strongly influenced by the external DOX layer. This method showed several benefits, including accelerating cellular uptake of the payloads and enabling chemo-photodynamic combination therapy for synergistic cancer treatment...
November 6, 2017: Colloids and Surfaces. B, Biointerfaces
Zhaopei Guo, Xingzhi Zhou, Mengze Xu, Huayu Tian, Xuesi Chen, Meiwan Chen
Camptothecin (CPT) is a broad spectrum anticancer drug, but its application is limited due to the poor water solubility, lactone ring instability, and low drug loading potential. In this study, biocompatible cationic polypeptide-based micelles were developed to deliver dimeric CPT (DCPT) with the aim of overcoming the above-mentioned obstacles and achieving favorable therapeutic effects. Cationic polypeptide poly-lysine-block-poly-leucine (PLys-b-PLeu) was fabricated via the ring-opening polymerization of N-ε-carbobenzoxy-l-lysine (ε-Lys(Z)) and l-leucine (Leu) and further grafted with polyethylene glycol (PEG) and an arginine-glycine-aspartic acid (RGD) peptide...
November 9, 2017: Biomaterials Science
Mohsin O Mohammed, Kameran S Hussain, Nadia Q Haj
5-fluorouracil (5-FU) is a specific anti-cancer agent that is generally used to treat gastrointestinal, colorectal, and breast cancer. In this work, chitosan (CS) was extracted from local fish scales using an established method. 5-FU was then converted to 1-acetic acid-5-fluorouracil (FUAC) and reacted with this CS to prepare chitosan-1-acetic acid-5-fluorouracil (CS-FUAC) conjugates as a colon-specific prodrug. All compounds were characterized by Proton nuclear magnetic resonance (¹H-NMR), Fourier-transform infrared (FTIR), and UV-visible spectroscopy...
November 8, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Longhai Jin, Jianhua Liu, Ying Tang, Lanqing Cao, Tianqi Zhang, Qinghai Yuan, Yinghui Wang, Hongjie Zhang
Construction of stimuli-responsive theranostic nanoagents that can improve the sensitivity of diagnostic imaging and boost the therapeutic efficiency has been demostrated to a promising approach for cancer diagnosis and treatment. Herein, we constructed a novel theranostic agent with Co-P nanocomposites as core, mesoporous silica as shell, and MnO2 nanosheets as "gatekeeper", which have been employed for pH-activatable T1/T2 dual mode MRI-guided chemo-photothermal combination anticancer therapy in vitro and in vivo...
November 8, 2017: ACS Applied Materials & Interfaces
Huachao Chen, Yurong Wang, Yongrong Yao, Shenglin Qiao, Hao Wang, Ninghua Tan
A programmed drug delivery system that can achieve sequential release of multiple therapeutics under different stimulus holds great promise to enhance the treatment efficacy and overcome multi-drug resistance (MDR) in tumor. Herein, multi-organelle-targeted and pH/ cytochrome c (Cyt c) dual-responsive nanoparticles were designed for combination therapy on resistant tumor. In this system (designated DGLipo NPs), doxorubicin (Dox) was intercalated into the DNA duplex containing a Cyt c aptamer, which subsequently loaded in the dendrigraftpoly-L-lysines (DGL) cores of DGLipo NPs, while cyclopeptide RA-V was doped into the pH-sensitive liposomal shells...
2017: Theranostics
Mohadeseh Hashemi, Meisam Omidi, Bharadwaj Muralidharan, Lobat Tayebi, Matthew J Herpin, Mohammad Ali Mohagheghi, Javad Mohammadi, Hugh D C Smyth, Thomas E Milner
Stimuli responsive polyelectrolyte nanoparticles have been developed for chemo-photothermal destruction of breast cancer cells. This novel system, called layer by layer Lipo-graph (LBL Lipo-graph), is composed of alternate layers of graphene oxide (GO) and graphene oxide conjugated poly (l-lysine) (GO-PLL) deposited on cationic liposomes encapsulating doxorubicin. Various concentrations of GO and GO-PLL were examined and the optimal LBL Lipo-graph was found to have a particle size of 267.9 ± 13 nm, zeta potential of +43...
November 8, 2017: Acta Biomaterialia
Lin-Lin Hu, Jie Meng, Dan-Dan Zhang, Ming-Li Chen, Yang Shu, Jian-Hua Wang
A multifunctional drug nanocarrier is developed by incorporating acetaldehyde-modified-cystine (AMC) into mesoporous organosilica nanoparticles (MONs), shortly termed as MONs-AMC. The anticancer drug doxorubicin (DOX) links directly to MONs-AMC through electrostatic interaction between DOX and AMC to produce a conjugate, MONs-AMC-DOX, with a drug loading efficiency of 26.24 ± 1.35%, corresponding to a loading capacity of 0.26 ± 0.01mgmg(-1) for DOX. Schiff base AMC contains a -S-S- bond and two -C˭N- bonds which cleave in the presence of certain level of GSH and in an acidic medium, providing MONs-AMC-DOX the capability for triggering pH and glutathione (GSH) dual-responsive drug release...
January 15, 2018: Talanta
Chun Kit K Choi, Xiaolu Zhuo, Yee Ting Elaine Chiu, Hongrong Yang, Jianfang Wang, Chung Hang Jonathan Choi
Nanoshells, classically comprising gold as the metallic component and silica as the dielectric material, are important for fundamental studies in nanoplasmonics. They also empower a myriad of applications, including sensing, energy harvesting, and cancer therapy. Yet, laborious preparation precludes the development of next-generation nanoshells with structural complexity, compositional diversity, and tailorable plasmonic behaviors. This work presents an efficient approach to the bottom-up assembly of concentric nanoshells...
November 9, 2017: Nanoscale
Zhi-Qiang Yuan, Wei-Liang Chen, Ben-Gang You, Yang Liu, Shu-di Yang, Ji-Zhao Li, Wen-Jing Zhu, Xiao-Feng Zhou, Chun Liu, Xue-Nong Zhang
Malignant proliferation and metastasis in non-small cell lung carcinoma (NSCLC) are great challenges for effective clinical treatment through conventional chemotherapy. The combinational therapy strategy of RNA interfering (RNAi) technology and chemotherapeutic agents have been reported to be promising for effective cancer therapy. In this study, based on multifunctional nanoparticles (NPs), the simultaneous delivery of etoposide (ETP) and anti-Enhancer of Zeste Homologue 2 (EZH2) siRNA for the effective treatment of orthotopic lung tumor was achieved...
October 20, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
Trong-Ming Don, Kun-Ying Lu, Li-Jie Lin, Chun-Hua Hsu, Jui-Yu Wu, Fwu-Long Mi
The tumor microenvironments are often acidic and overexpress specific enzymes. In this work, we synthesized a poly(AA-b-NIPAAm) copolymer (PAA-b-PNIPAAm) using a reversible addition-fragmentation chain transfer (RAFT) polymerization method. PAA-b-PNIPAAm and a cationic protein (protamine) were self-assembled into nanogels, which effectively reduced the cytotoxicity of protamine. The protamine/PAA-b-PNIPAAm nanogels were responsive to the stimuli including temperature, pH and enzyme due to disaggregation of PAA-b-PNIPAAm, change in random coil/α-helix conformation of protamine, and enzymatic hydrolysis of the protein...
October 23, 2017: Molecular Pharmaceutics
Qing Guo, Xian-Tao Shen, Yuan-Yuan Li, Shun-Qing Xu
Current treatments for cancer and the central nervous system diseases are limited, partly due to the difficulties posed by the insolubility, poor distribution of drugs among cells and lack of selectivity of drugs, the inability of drugs to cross cellular barriers and blood brain barrier (BBB). Carbon nanotubes (CNTs) possess many distinct properties including good electronic properties, remarkably penetrating capability on the cell membrane, high drug-loading and pH-dependent therapeutic unloading capacities, thermal properties, large surface area and easy modification with molecules, which render them as a suitable candidate to deliver drugs to cancer and brain...
October 2017: Journal of Huazhong University of Science and Technology. Medical Sciences
Min Hee Lee, Amit Sharma, Min Jung Chang, Jinju Lee, Subin Son, Jonathan L Sessler, Chulhun Kang, Jong Seung Kim
Theranostic systems are receiving ever-increasing attention due to their potential therapeutic utility, imaging enhancement capability, and promise for advancing the field of personalized medicine, particularly as it relates to the diagnosis, staging, and treatment of cancer. In this Tutorial Review, we provide an introduction to the concepts of theranostic drug delivery effected via use of conjugates that are able to target cancer cells selectively, provide cytotoxic chemotherapeutics, and produce readily monitored imaging signals in vitro and in vivo...
October 23, 2017: Chemical Society Reviews
Soyoung Son, Sol Shin, N Vijayakameswara Rao, Wooram Um, Jueun Jeon, Hyewon Ko, V G Deepagan, Seunglee Kwon, Jun Young Lee, Jae Hyung Park
Trop2, a transmembrane glycoprotein, has emerged as a biomarker for targeted cancer therapy since it is overexpressed in 80% of triple negative breast cancer (TNBC) patients. For the site-specific delivery of the anticancer drug into TNBC, anti-Trop2 antibody-conjugated nanoparticles (ST-NPs) were prepared as the potential nanocarrier, composed of carboxymethyl dextran (CMD) derivatives with bioreducible disulfide bonds. Owing to its amphiphilicity, the CMD derivatives were self-assembled into nano-sized particles in an aqueous condition...
October 18, 2017: International Journal of Biological Macromolecules
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