Multifunctional polymeric nanoparticles for combined chemotherapeutic and near-infrared photothermal cancer therapy in vitro and in vivo

2010 ◽  
Vol 46 (18) ◽  
pp. 3167 ◽  
Author(s):  
Fong-Yu Cheng ◽  
Chia-Hao Su ◽  
Ping-Ching Wu ◽  
Chen-Sheng Yeh
Pharmaceutics ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 507 ◽  
Author(s):  
Liu ◽  
Gao ◽  
Zhou ◽  
Nie ◽  
Cheng ◽  
...  

Abstract: The development of versatile nanoscale drug delivery systems that integrate with multiple therapeutic agents or methods and improve the efficacy of cancer therapy is urgently required. To satisfy this demand, polydopamine (PDA)-modified polymeric nanoplatforms were constructed for the dual loading of chemotherapeutic drugs. The hydrophobic anticancer drug docetaxel (DTX) was loaded into the polymeric nanoparticles (NPs) which were fabricated from the star-shaped copolymer CA-PLGA. Then DTX-loaded NPs were coated with PDA, followed by conjugation of polyelethyl glycol (PEG)-modified targeting ligand aptamer AS1411(Apt) and adsorption of the hydrophilic anticancer drug doxorubicin (DOX). This “four-in-one” nanoplatform, referred to as DTX/NPs@PDA/DOX-PEG-Apt, demonstrated high near-infrared photothermal conversion efficiency and exhibited pH and thermo-responsive drug release behavior. Furthermore, it was able to specifically target MCF-7 human breast carcinoma cells and provide synergistic chemo-photothermal therapy to further improve the anticancer effect both in vitro and in vivo, providing a novel promising strategy for cancer therapy.


2014 ◽  
Vol 5 ◽  
pp. 313-322 ◽  
Author(s):  
Tingjun Lei ◽  
Alicia Fernandez-Fernandez ◽  
Romila Manchanda ◽  
Yen-Chih Huang ◽  
Anthony J McGoron

Background: In the past decade, researchers have focused on developing new biomaterials for cancer therapy that combine imaging and therapeutic agents. In our study, we use a new biocompatible and biodegradable polymer, termed poly(glycerol malate co-dodecanedioate) (PGMD), for the synthesis of nanoparticles (NPs) and loading of near-infrared (NIR) dyes. IR820 was chosen for the purpose of imaging and hyperthermia (HT). HT is currently used in clinical trials for cancer therapy in combination with radiotherapy and chemotherapy. One of the potential problems of HT is that it can up-regulate hypoxia-inducible factor-1 (HIF-1) expression and enhance vascular endothelial growth factor (VEGF) secretion. Results: We explored cellular response after rapid, short-term and low thermal dose laser-IR820-PGMD NPs (laser/NPs) induced-heating, and compared it to slow, long-term and high thermal dose heating by a cell incubator. The expression levels of the reactive oxygen species (ROS), HIF-1 and VEGF following the two different modes of heating. The cytotoxicity of NPs after laser/NP HT resulted in higher cell killing compared to incubator HT. The ROS level was highly elevated under incubator HT, but remained at the baseline level under the laser/NP HT. Our results show that elevated ROS expression inside the cells could result in the promotion of HIF-1 expression after incubator induced-HT. The VEGF secretion was also significantly enhanced compared to laser/NP HT, possibly due to the promotion of HIF-1. In vitro cell imaging and in vivo healthy mice imaging showed that IR820-PGMD NPs can be used for optical imaging. Conclusion: IR820-PGMD NPs were developed and used for both imaging and therapy purposes. Rapid and short-term laser/NP HT, with a low thermal dose, does not up-regulate HIF-1 and VEGF expression, whereas slow and long term incubator HT, with a high thermal dose, enhances the expression of both transcription factors.


2015 ◽  
Vol 51 (49) ◽  
pp. 10054-10057 ◽  
Author(s):  
Qin Liu ◽  
Chunyang Sun ◽  
Qun He ◽  
Daobin Liu ◽  
Adnan Khalil ◽  
...  

Uniform MoO2 nanoparticles coated with ultrathin carbon layers, synthesized by a solvothermal method, were demonstrated as a promising NIR photothermal agent by in vitro and in vivo tests.


2020 ◽  
Vol 27 (15) ◽  
pp. 2494-2513 ◽  
Author(s):  
João A. Oshiro-Júnior ◽  
Camila Rodero ◽  
Gilmar Hanck-Silva ◽  
Mariana R. Sato ◽  
Renata Carolina Alves ◽  
...  

Stimuli-responsive drug-delivery nanocarriers (DDNs) have been increasingly reported in the literature as an alternative for breast cancer therapy. Stimuli-responsive DDNs are developed with materials that present a drastic change in response to intrinsic/chemical stimuli (pH, redox and enzyme) and extrinsic/physical stimuli (ultrasound, Near-infrared (NIR) light, magnetic field and electric current). In addition, they can be developed using different strategies, such as functionalization with signaling molecules, leading to several advantages, such as (a) improved pharmaceutical properties of liposoluble drugs, (b) selectivity with the tumor tissue decreasing systemic toxic effects, (c) controlled release upon different stimuli, which are all fundamental to improving the therapeutic effectiveness of breast cancer treatment. Therefore, this review summarizes the use of stimuli-responsive DDNs in the treatment of breast cancer. We have divided the discussions into intrinsic and extrinsic stimuli and have separately detailed them regarding their definitions and applications. Finally, we aim to address the ability of these stimuli-responsive DDNs to control the drug release in vitro and the influence on breast cancer therapy, evaluated in vivo in breast cancer models.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14637-e14637
Author(s):  
Andrew Gdowski ◽  
Amalendu Ranjan ◽  
Jana Lampe ◽  
Victor Lin ◽  
Yu-Chieh Wang ◽  
...  

e14637 Background: We have engineered a programmable-bioinspired nanoparticle (P-BiNP) delivery system to simultaneously target the bone and increase uptake in homotypic tumor cells by coating polymeric nanoparticles with programmed cancer cell membranes. This approach is unique in that we have incorporated relevant clinical bioinformatics data to guide the design of these nanoparticles. Methods: A gene ontology search identified potential homotypic cell-cell adhesion genes. These were cross referenced with RNAseq expression levels from patients with metastatic prostate cancer to various organ locations using the Cbioportal database. C4-2B prostate cancer cells were grown and stimulated to express membrane ɑVβ3 by treatment with recombinant human CXCL12. The cell membrane from these cancer cells were used to coat polymeric nanoparticles by an extrusion process. Physico-chemical optimization and characterization of the P-BiNPs was performed. In vitro testing was done with flow cytometry and MTT assays. A murine model was used with high resolution near infrared imaging to identify nanoparticle localization. Results: Analysis of RNAseq from mCRPC samples (n = 118) identified ITGB3 as increased in bone metastatic lesions compared to metastases from other sites (P < 0.0001). ITGB3 is a subunit of integrin ɑVβ3 and was selected as a target for enhancement to improve P-BiNP homotypic targeting and bone localization. After optimization, P-BiNPs showed optimal physico-chemical characteristics for drug delivery. Both in vitro testing and in vivo testing showed the P-BiNPs to be superior in homotypic uptake and localization to the bone. Conclusions: This platform of identifying clinically relevant targets for dual homotypic and bone targeting has potential as a strategy for treatment and imaging modalities in cancers that affects the bone as well as implications for delivering nanoparticles to other organs of interest.


2020 ◽  
Vol 10 (8) ◽  
pp. 1204-1212
Author(s):  
Tengbiao Ma ◽  
Xue Guan ◽  
Dan Wu ◽  
Xinxia Wang ◽  
Yali Cui

For cancer diagnosis and therapeutics, we adopted a novel strategy and established a new approach by using transarterial administration of gold nanoshells on silica nanorattles (GSNs) for multifunctional biomedical application. The GSNs exhibit high biocompatibility and stability in vitro and in vivo. It was found that an arterial administration of GSNs showed six-fold higher efficiency than the venous method. In this study, we found that the system of using GSNs had a high near-infrared (NIR) absorbance and excellent photothermal transfer capability for cancer photothermal therapy (PTT) efficiently. More importantly, the GSN treatment method, involving interventional procedures and nanomaterials, showed great potential to promote tumor apoptosis in all research. Using CT imaging technology, we monitored the volume change of tumors and confirmed cell apoptosis by TUNEL staining and immunohistochemistry. Furthermore, arterial administration of GSNs combined with NIR irradiation was established, and the related proteins was examined by Western blotting. Caspase-3 and 9 showed an high expression level within tumor tissues. Finally, a comparative study of biodistribution and safety was performed in vivo, and the biocompatibility was carefully evaluated. This GSN-based method was ultimately shown to be a promising approach for cancer therapy.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 235
Author(s):  
Luana Zerrillo ◽  
Karthick Babu Sai Sankar Gupta ◽  
Fons A.W.M. Lefeber ◽  
Candido G. Da Silva ◽  
Federica Galli ◽  
...  

Polymeric nanoparticles (NPs) find many uses in nanomedicine, from drug delivery to imaging. In this regard, poly (lactic-co-glycolic acid) (PLGA) and polyethylene glycol (PEG) particles are the most widely applied types of nano-systems due to their biocompatibility and biodegradability. Here we developed novel fluorinated polymeric NPs as vectors for multi-modal nanoprobes. This approach involved modifying polymeric NPs with trifluoroacetamide (TFA) and loading them with a near-infrared (NIR) dye for different imaging modalities, such as magnetic resonance imaging (MRI) and optical imaging. The PLGA-PEG-TFA NPs generated were characterized in vitro using the C28/I2 human chondrocyte cell line and in vivo in a mouse model of osteoarthritis (OA). The NPs were well absorbed, as confirmed by confocal microscopy, and were non-toxic to cells. To test the NPs as a drug delivery system for contrast agents of OA, the nanomaterial was administered via the intra-articular (IA) administration method. The dye-loaded NPs were injected in the knee joint and then visualized and tracked in vivo by fluorine-19 nuclear magnetic resonance and fluorescence imaging. Here, we describe the development of novel intrinsically fluorinated polymeric NPs modality that can be used in various molecular imaging techniques to visualize and track OA treatments and their potential use in clinical trials.


Author(s):  
Huazhong Cai ◽  
Yanxia Chen ◽  
Liusheng Xu ◽  
Yingping Zou ◽  
Xiaoliang Zhou ◽  
...  

In this study, a chemically synthetic polymer, benzo[1,2-b:4,5-b′]difuran(BDF)-based donor–acceptor copolymer PBDFDTBO, was individually coated by amphiphilic poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-PCL) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(polyethylene glycol) (DSPE-PEG or PEG-DSPE), to form stably fluorescent nanoparticles in the near-infrared (NIR) window. The physicochemical properties of the synthesized nanoparticles were characterized and compared, including their size, surface charge, and morphology. In addition, in vitro studies were also performed using two pancreatic cancer cell lines, assessing the cell viability of the PBDFDTBO-included PEGylated nanoparticles formulations. Moreover, in vivo studies were also conducted, using subcutaneous murine cancer models to investigate the polymeric nanoparticles’ circulation time, tumor accumulation, and preferred organ biodistribution. The overall results demonstrated that even with the same PEGylated surface, the hydrophobic composition anchored on the encapsulated PBDFDTBO core strongly affected the biodistribution and tumor accumulation of the nanoparticles, to a degree possibly determined by the hydrophobic interactions between the hydrophobic segment of amphiphilic polymers (DSPE or PCL moiety) and the enwrapped PBDFDTBO. Both PEGylated nanoparticles were compared to obtain an optimized coating strategy for a desired biological feature in pancreatic cancer delivery.


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