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Nanoparticles intratumoral injection

Xiao-Yang Chu, Wei Huang, Yu-Li Wang, Ling-Wei Meng, Li-Qing Chen, Ming-Ji Jin, Lu Chen, Chun-Hong Gao, Cheng Ge, Zhong-Gao Gao, Chun-Sheng Gao
Background: Intratumoral injection is a palliative treatment that aims at further improvement in the survival and quality of life of patients with advanced or recurrent carcinomas, or cancer patients with severe comorbidities or those with a poor performance status. Methods: In this study, a solvent-injection method was used to prepare paclitaxel-cholesterol complex-loaded lecithin-chitosan nanoparticles (PTX-CH-loaded LCS_NPs) for intratumoral injection therapy, and the physicochemical properties of NPs were well characterized...
2019: International Journal of Nanomedicine
Ajay A Sapre, Gen Yong, Ya-San Yeh, Laura E Ruff, Justin S Plaut, Zeynep Sayar, Anupriya Agarwal, Jacqueline Martinez, Theresa N Nguyen, Yu-Tsueng Liu, Bradley T Messmer, Sadik C Esener, Jared M Fischer
Viral gene therapy is a means of delivering genes to replace malfunctioning ones, to kill cancer cells, or to correct genetic mutations. This technology is emerging as a powerful clinical tool; however, it is still limited by viral tropism, uptake and clearance by the liver, and most importantly an immune response. To overcome these challenges, we sought to merge the robustness of viral gene expression and the versatility of nanoparticle technology. Here, we describe a method for cloaking adenovirus (Ad) in silica (SiAd) as a nanoparticle formulation that significantly enhances transduction...
January 25, 2019: Journal of Controlled Release: Official Journal of the Controlled Release Society
Liqun Huang, Chang Xu, Peng Xu, Yu Qin, Mengwei Chen, Qishuai Feng, Jing Pan, Qian Cheng, Feng Liang, Xiaofei Wen, Ying Wang, Yufang Shi, Yu Cheng
Targeted delivery of nanomedicines into the tumor site and improving the intratumoral distribution remain challenging in cancer treatment. Here, we report an effective transportation system utilizing both of mesenchymal stem cells (MSCs) and their secreted microvesicles containing assembled gold nanostars (GNS) for targeted photothermal therapy of prostate cancer. The stem cells act as a cell carrier to actively load and assemble GNS into the lysosomes. Accumulation of GNS in the lysosomes facilitates the close interaction of nanoparticles, which could result in a 20 nm red-shift of surface plasmon resonance of GNS with a broad absorption in the near infrared region...
2019: Nanotheranostics
Xiujie Huang, Changliang Xu, Yichen Li, Haibo Cheng, Xiaoying Wang, Runcang Sun
In this study, we report a smart and green strategy to synthesize copper sulfide nanoparticles (CuS-NPs) for clinically translatable cancer treatment. For the first time, the preparation of CuS-NPs was developed by taking advantage of the copper-amine complex as the copper source and sodium sulfide as the sulfide source, in which the quaternized chitosan (QCS) was used as a biotemplate and stabilizing agent. The obtained QCS/CuS-NPs composites (CuS@QCS-NPs) were spherical and stable with an average diameter of 5...
March 2019: Materials Science & Engineering. C, Materials for Biological Applications
Gerald L Wolf
All malignancies contain tumor-associated macrophages (TAMs) that facilitate cancer growth by secreting chemicals to elicit angiogenesis and shield the cancer from the immune system. The abundance of TAMs is a reflection of invasiveness and metastatic potential. TAMs will actively ingest ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles following intravenous administration and will store them as large lysosomal aggregates which can be imaged with MRI and ultrasound and visualized or quantitated in tissue biopsies...
January 2019: Medical Hypotheses
Joel A Finbloom, Ioana L Aanei, Jenna M Bernard, Sarah H Klass, Susanna K Elledge, Kenneth Han, Tomoko Ozawa, Theodore P Nicolaides, Mitchel S Berger, Matthew B Francis
Glioblastoma is a particularly challenging cancer, as there are currently limited options for treatment. New delivery routes are being explored, including direct intratumoral injection via convection-enhanced delivery (CED). While promising, convection-enhanced delivery of traditional chemotherapeutics such as doxorubicin (DOX) has seen limited success. Several studies have demonstrated that attaching a drug to polymeric nanoscale materials can improve drug delivery efficacy via CED. We therefore set out to evaluate a panel of morphologically distinct protein nanoparticles for their potential as CED drug delivery vehicles for glioblastoma treatment...
December 5, 2018: Nanomaterials
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
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