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Nanoparticles intratumoral injection

Meiling Yu, Chunxue Zhang, Zhaohui Tang, Xing Tang, Hui Xu
Intratumoral injection of chemotherapy agents may be employed in the treatment of cancers. However, its anti-tumor efficacy is significantly impeded by collagen fibers in the tumor which decrease drug penetration into the tumor tissues. To improve the penetration, collagen inhibiting drug exposure is required. In this study, microspheres were fabricated by the modified double emulsion-solvent evaporation method as the drug delivery system of losartan potassium (LP MSs), with 5% gelatin as the inner phase. The collagen inhibiting experiment analyzed by Sirius Red stains demonstrated that LP MSs may effectively inhibit collagen I synthesis in B16 tumors...
November 12, 2018: Cancer Letters
Simo Näkki, Julie T-W Wang, Jianwei Wu, Li Fan, Jimi Rantanen, Tuomo Nissinen, Mikko I Kettunen, Matilda Backholm, Robin H A Ras, Khuloud T Al-Jamal, Vesa-Pekka Lehto, Wujun Xu
The inability of traditional chemotherapeutics to reach cancer tissue reduces the treatment efficacy and leads to adverse effects. A multifunctional nanovector was developed consisting of porous silicon, superparamagnetic iron oxide, calcium carbonate, doxorubicin and polyethylene glycol. The particles integrate magnetic properties with the capacity to retain drug molecules inside the pore matrix at neutral pH to facilitate drug delivery to tumor tissues. The MRI applicability and pH controlled drug release were examined in vitro together with in-depth material characterization...
November 2, 2018: International Journal of Pharmaceutics
Longlong Tian, Xuan Yi, Ziliang Dong, Jun Xu, Chao Liang, Yu Chao, Yaxing Wang, Kai Yang, Zhuang Liu
Tumor-associated macrophages (TAMs) are often related with poor prognosis after radiotherapy. Depleting TAMs may thus be a promising method to improve the radio-therapeutic efficacy. Herein, we report a biocompatible and biodegradable nanoplatform based on calcium bisphosphonate (CaBP-PEG) nanoparticles for chelator-free radiolabeling chemistry, effective in vivo depletion of TAMs, and imaging-guided enhanced cancer radioisotope therapy (RIT). It is found that CaBP-PEG nanoparticles prepared via a mineralization method with poly(ethylene glycol) (PEG) coating could be labeled with various radioisotopes upon simple mixing, including gamma-emitting 99m Tc for single-photon-emission computed tomography (SPECT) imaging, as well as beta-emitting 32 P as a therapeutic radioisotope for RIT...
November 27, 2018: ACS Nano
Chang Xu, Qishuai Feng, Haocheng Yang, Guangxue Wang, Liqun Huang, Qianwen Bai, Chuyi Zhang, Yilong Wang, Yingna Chen, Qian Cheng, Mengwei Chen, Yu Han, Zuoren Yu, Maciej S Lesniak, Yu Cheng
Targeted therapy is highly challenging and urgently needed for patients diagnosed with triple negative breast cancer (TNBC). Here, a synergistic treatment platform with plasmonic-magnetic hybrid nanoparticle (lipids, doxorubicin (DOX), gold nanorods, iron oxide nanocluster (LDGI))-loaded mesenchymal stem cells (MSCs) for photoacoustic imaging, targeted photothermal therapy, and chemotherapy for TNBC is developed. LDGI can be efficiently taken up into the stem cells with good biocompatibility to maintain the cellular functions...
October 2018: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
Gil Covarrubias, Anthony Cha, Abdelrahman Rahmy, Morgan Lorkowski, Vindya Perera, Bernadette O Erokwu, Chris Flask, Pubudu M Peiris, William P Schiemann, Efstathios Karathanasis
Nanoparticles often only exploit the upregulation of a receptor on cancer cells to enhance intratumoral deposition of therapeutic and imaging agents. However, a single targeting moiety assumes that a tumor is homogenous and static. Tumoral microenvironments are both heterogenous and dynamic, often displaying variable spatial and temporal expression of targetable receptors throughout disease progression. Here, we evaluated the in vivo performance of an iron oxide nanoparticle in terms of targeting and imaging of orthotropic mouse models of aggressive breast tumors...
2018: PloS One
Limei Shen, Jingjing Li, Qi Liu, Wantong Song, Xueqiong Zhang, Karthik Tiruthani, Haiyang Hu, Manisit Das, Tyler Jay Goodwin, Rihe Liu, Leaf Huang
In many cancers, the tumor microenvironment (TME) is largely immune suppressive, blocking the antitumor immunity and resulting in immunotherapy resistance. Interleukin 10 (IL-10) is a major player controlling the immunosuppressive TME in different murine tumor models. Increased IL-10 production suppresses intratumoral dendritic cell production of interleukin 12, thereby limiting antitumor cytotoxic T-cell responses and activation of NK cells during therapy. We engineered, formulated, and delivered genes encoding an IL-10 protein trap to change immunosuppressive TME, which could enhance antitumor immunity...
September 28, 2018: ACS Nano
Nadia Saadat, Fangchao Liu, Brittany Haynes, Pratima Nangia-Makker, Xun Bao, Jing Li, Lisa Polin, Smiti Gupta, Guangzhao Mao, Malathy P Shekhar
The triple negative breast cancer (TNBC) subtype regardless of their BRCA1 status has the poorest outcome compared to other breast cancer subtypes and currently there are no approved targeted therapies for TNBC. We have previously demonstrated the importance of Rad6-mediated translesion synthesis pathway in TNBC development/progression and chemoresistance, and the potential therapeutic benefit of targeting Rad6 with a Rad6-selective small molecule inhibitor SMI#9. To overcome SMI#9 solubility limitations, we recently developed a gold nanoparticle (GNP)-based platform for conjugation and intracellular release of SMI#9, and demonstrated its in vitro cytotoxic activity towards TNBC cells...
September 21, 2018: Molecular Cancer Therapeutics
Dafei Chai, Nianli Liu, Huizhong Li, Gang Wang, Jingyuan Song, Lin Fang, Zheng Lu, Hong Yao, Junnian Zheng
Renal cell carcinoma (RCC) is a high metastasis tumour with less effective treatment available currently. Absent in melanoma 2 (AIM2) as a tumour suppressor might be used as a potential therapeutic target for RCC treatment. Here, we found that AIM2 expression was significantly decreased in RCC patient specimens and renal carcinoma cell lines (786-O and OSRC-2). To establish a safe and effective AIM2 gene delivery system, we formed the nanoparticles consisting of a folate grafted PEI600-CyD (H1) nanoparticle-mediated AIM2 gene (H1/pAIM2) as an effective delivery agent...
November 2018: Journal of Cellular and Molecular Medicine
Xueyan Zhang, Fengbo Wu, Ke Men, Rong Huang, Bailin Zhou, Rui Zhang, Rui Zou, Li Yang
As a novel toll-like receptor 9 (TLR9) agonist, synthetic unmethylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotides can stimulate a Th1 immune response and potentially be used as therapeutic agents or vaccine adjuvants for the treatment of cancer. However, some drawbacks of CpG limit their applications, such as rapid elimination by nuclease-mediated degradation and poor cellular uptake. Therefore, repeat high-dose drug administration is required for treatment. In this work, a CpG delivery system based on 3-aminopropyltriethoxysilane (APTES)-modified Fe3 O4 nanoparticles (FeNPs) was designed and studied for the first time to achieve better bioactivity of CpG...
August 17, 2018: Nanoscale Research Letters
Silvia Mannucci, Stefano Tambalo, Giamaica Conti, Leonardo Ghin, Alessio Milanese, Anna Carboncino, Elena Nicolato, Maria Rosaria Marinozzi, Donatella Benati, Roberto Bassi, Pasquina Marzola, Andrea Sbarbati
Magnetic fluid hyperthermia (MFH) with chemically synthesized nanoparticles is currently used in clinical trials as it destroys tumor cells with an extremely localized deposition of thermal energy. In this paper, we investigated an MFH protocol based on magnetic nanoparticles naturally produced by magnetotactic bacteria: magnetosomes. The efficacy of such protocol is tested in a xenograft model of glioblastoma. Mice receive a single intratumoral injection of magnetosomes, and they are exposed three times in a week to an alternating magnetic field with concurrent temperature measurements...
2018: Contrast Media & Molecular Imaging
Te-I Liu, Ying-Chieh Yang, Wen-Hsuan Chiang, Chun-Kai Hung, Yuan-Chung Tsai, Chi-Shiun Chiang, Chun-Liang Lo, Hsin-Cheng Chiu
Radiotherapy is one of the general approaches to deal with malignant solid tumors in clinical treatment. To improve therapeutic efficacy, chemotherapy is frequently adopted as the adjuvant treatment in combination with radiotherapy. In this work, a reactive oxygen species (ROS)-responsive nanoparticle (NP) drug delivery system was developed to synergistically enhance the antitumor efficacy of radiotherapy by local ROS-activated chemotherapy, taking advantages of the enhanced concentration of reactive oxygen species (ROS) in tumor during X-ray irradiation and/or reoxygenation after X-ray irradiation...
September 10, 2018: Biomacromolecules
Lihua Luo, Chunqi Zhu, Hang Yin, Mengshi Jiang, Junlei Zhang, Bing Qin, Zhenyu Luo, Xiaoling Yuan, Jie Yang, Wei Li, Yongzhong Du, Jian You
A convenient and feasible therapeutic strategy for malignant and metastatic tumors was constructed here by combining photothermal ablation (PTA)-based laser immunotherapy with perdurable PD-1 blockade immunotherapy. Hollow gold nanoshells (HAuNS, a photothermal agent) and AUNP12 (an anti PD-1 peptide, APP) were co-encapsulated into poly(lactic- co-glycolic) acid (PLGA) nanoparticles. Unlike monoclonal PD-1/PD-L1 antibodies, PD-1 peptide inhibitor shows lower cost and immunotoxicity but needs frequent administration due to its rapid clearance in vivo...
August 28, 2018: ACS Nano
Henry M Smilowitz, Alexandria Meyers, Khalil Rahman, Nathaniel A Dyment, Dan Sasso, Crystal Xue, Douglas L Oliver, Alexander Lichtler, Xiaomeng Deng, Sharif M Ridwan, Lauren J Tarmu, Qian Wu, Andrew L Salner, Ketan R Bulsara, Daniel N Slatkin, James F Hainfeld
Background: Intravenously (IV)-injected gold nanoparticles (AuNPs) powerfully enhance the efficacy of X-ray therapy of tumors including advanced gliomas. However, pharmacokinetic issues, such as slow tissue clearance and skin discoloration, may impede clinical translation. The direct infusion of AuNPs into the tumor might be an alternative mode of delivery. Materials and methods: Using the advanced, invasive, and difficult-to-treat F98 rat glioma model, we have studied the biodistribution of the AuNPs in the tumor and surrounding brain after either IV injection or direct intratumoral infusion by convection-enhanced delivery using light microscopy immunofluorescence and direct gold visualization...
2018: International Journal of Nanomedicine
Long Yuan, Fan Zhang, Xiaowei Qi, Yongjun Yang, Chang Yan, Jun Jiang, Jun Deng
BACKGROUND: Autophagy regulation through exogenous materials has aroused intensive attention to develop treatment protocols according to diverse human diseases. However, to the best of our knowledge, few examples have been reported to selectively control autophagy process and ultimately achieve efficient therapeutic potential. RESULTS: In this study, monolayers of poly (acryloyl-L, D and racemic valine) (L-PAV-AuNPs, D-PAV-AuNPs and L/D-PAV-AuNPs) chiral molecules were anchored on the surfaces of gold nanoparticles (PAV-AuNPs), and the subsequent chirality-selective effects on autophagy activation were thoroughly studied...
July 11, 2018: Journal of Nanobiotechnology
Tamer M Sakr, O M Khowessah, M A Motaleb, A Abd El-Bary, M T El-Kolaly, Mohamed M Swidan
Nanotechnology may be applied in medicine where the utilization of nanoparticles (≤100 nm) for the delivery and targeting of theranostic agents is at the forefront of projects in cancer nano-science. This study points a novel one step synthesis approach to build up polyethylene glycol capped silver nanoparticles doped with I-131 radionuclide (131 I-doped Ag-PEG NPs). The formula was prepared with average hydrodynamic size 21 nm, zeta potential - 25 mV, radiolabeling yield 98 ± 0.76%, and showed good in-vitro stability in saline and mice serum...
September 15, 2018: European Journal of Pharmaceutical Sciences
Huang-Chiao Huang, Michael Pigula, Yanyan Fang, Tayyaba Hasan
The past three decades have witnessed notable advances in establishing photosensitizer-antibody photo-immunoconjugates for photo-immunotherapy and imaging of tumors. Photo-immunotherapy minimizes damage to surrounding healthy tissue when using a cancer-selective photo-immunoconjugate, but requires a threshold intracellular photosensitizer concentration to be effective. Delivery of immunoconjugates to the target cells is often hindered by I) the low photosensitizer-to-antibody ratio of photo-immunoconjugates and II) the limited amount of target molecule presented on the cell surface...
July 1, 2018: Small
Maryam A Shetab Boushehri, Mona M A Abdel-Mottaleb, Arnaud Béduneau, Yann Pellequer, Alf Lamprecht
This study sought to develop a simple nanoparticle-based approach to enhance the efficiency and tolerability of lipopolysaccharide (LPS), a potent ligand of Toll-like Receptor 4 (TLR4), for immunotherapy in cancer. Despite holding promise within this context, the strong pro-inflammatory properties of LPS also account for its low tolerability given localized and systemic side effects, which restrict the administrable dosage. Herein, we investigated the effect of LPS decoration as a surface-active molecule on a polymeric matrix upon its efficiency and tolerability...
November 2018: Drug Delivery
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%)...
July 9, 2018: Biomacromolecules
Raj Kumar Thapa, Zar Chi Soe, Wenquan Ou, Kishwor Poudel, Jee-Heon Jeong, Sung Giu Jin, Sae Kwang Ku, Han-Gon Choi, You Mie Lee, Chul Soon Yong, Jong Oh Kim
Intratumoral injection of nanoparticles is a viable alternative for treating solid tumors. In this study, we used intratumorally-injected palladium nanoparticle (Pd NP)-decorated graphene oxide (GO) (GO-Pd NPs) for the treatment of solid prostate tumors. GO was synthesized using the modified Hummer's method and GO-Pd NPs were prepared using the one pot synthesis method. Studies on physicochemical characterization and in vitro/in vivo anticancer properties were performed using GO-Pd NPs. Successful preparation of GO-Pd NPs was confirmed by transmission electron microscopy, Fourier transform infrared spectroscopy, energy dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy...
May 23, 2018: Colloids and Surfaces. B, Biointerfaces
Jinghua Sun, Wen Xu, Liping Li, Bo Fan, Xiaoyang Peng, Botao Qu, Lingjie Wang, Tingting Li, Sijin Li, Ruiping Zhang
Multi-modal imaging-guided photothermal therapy (PTT) has aroused extensive attention in biomedical research recently because it can provide more comprehensive information for accurate diagnosis and treatment. In this research, the manganese ion chelated endogenous biopolymer melanin nanoparticles were successfully prepared for magnetic resonance (MR)/photoacoustic (PA) dual-modal imaging-guided PTT. The obtained nanoparticles with an ultrasmall size of about 3.2 nm exhibited negligible cytotoxicity, high relaxivity for MRI, an excellent photothermal effect and PA activity...
June 7, 2018: Nanoscale
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