Tumor-homing multifunctional nanoparticles for cancer theragnosis: Simultaneous diagnosis, drug delivery, and therapeutic monitoring

Kim, Kwangmeyung; Kim, Jong Ho; Park, Hyungkyu; Kim, Yoo Shin; Park, Kyeongsoon; Nam, Heayun; Lee, Seulki; Park, Jae Hyung; Park, Rang Woon; Kim, In San; Choi, Kuiwon; Kim, Sang Yoon; Park, Kinam; Kwon, Ick Chan

doi:10.1016/j.jconrel.2010.04.004

Cited by 324 publications

(245 citation statements)

References 22 publications

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“…In line with the literature, [21][22][23][24][25][26][27][28][29][30][31] comparing 2D FRI to 3D FMT showed that the latter more realistically reflected the biodistribution of pHPMA-Dy750 than the former (which essentially only indicated highly effective and highly selective probe accumulation in tumors; see upper panels in Figure 2B). Taking previous results obtained with regard to the biodistribution of radiolabeled HPMA-based polymeric drug carriers into account, 12,34,[36][37][38][39] however, also 3D FMT did not properly reflect tumor and healthy organ accumulation.…”

Section: Resultssupporting

confidence: 88%

“…[16][17][18][19][20][21][22][23][24][25] FRI is generally considered to be an excellent tool for monitoring nanomedicine accumulation in superficial tissues, such as subcutaneously inoculated tumors, but it is unable to provide quantitative information, and it also does not allow for the assessment of nanomedicine accumulation in deeper-seated tissues. 26 This means that it can be used for qualitative and comparative analyses, in which e.g.…”

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confidence: 99%

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Noninvasive Optical Imaging of Nanomedicine Biodistribution

et al. 2012

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Nanomedicines are submicrometer-sized carrier materials designed to improve the biodistribution of i.v. administered (chemo-) therapeutic agents. In recent years, ever more efforts in the nanomedicine field have employed optical imaging (OI) techniques to monitor biodistribution and target site accumulation. Thus far, however, the longitudinal assessment of nanomedicine biodistribution using OI has been impossible, due to limited light penetration (in case of 2D fluorescence reflectance imaging; FRI), and to the inability to accurately allocate fluorescent signals to non-superficial organs (in case of 3D fluorescence molecular tomography; FMT). Using a combination of high-resolution micro-computed tomography (μCT) and FMT, we have here set out to establish a hybrid imaging protocol for non-invasively visualizing and quantifying the accumulation of near-infrared fluorophore-labeled nanomedicines in tissues other than superficial tumors. To this end, HPMA-based polymeric drug carriers were labeled with Dy750, their biodistribution and tumor accumulation were analyzed using FMT, and the resulting data sets were fused with anatomical μCT data sets in which several different physiologically relevant organs were pre-segmented. The robustness of 3D organ segmentation was validated, and the results obtained using 3D CT-FMT were compared to those obtained upon standard 3D FMT and 2D FRI. Our findings convincingly demonstrate that combining anatomical μCT with molecular FMT facilitates the non-invasive assessment of nanomedicine biodistribution. KeywordsNanomedicine; Drug targeting; Biodistribution; FMT; FRI; CT Nanomedicines aim to deliver drugs and imaging agents more efficiently and more specifically to pathological sites. A significant amount of evidence has been obtained over the years exemplifying the superiority of nanomedicine formulations over free drugs, both at the preclinical and at the clinical level. [1][2][3][4][5] Prototypic examples of nanomedicine formulations are liposomes, polymers, micelles and nanoparticles. These submicrometersized carrier materials are designed to modulate the pharmacokinetics and the biodistribution of conjugated or entrapped (chemo-) therapeutic drugs. Upon intravenous (i.v.)

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Section: Resultssupporting

confidence: 88%

mentioning

confidence: 99%

Noninvasive Optical Imaging of Nanomedicine Biodistribution

et al. 2012

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“…Koremeyer-Peppas which is a semi-empirical formula was used to describe the drug release mechanism. The 'n'value of 0.84 confirms the non-Fickian mode of release which suggests diffusion and erosion are the main mechanisms of action [18].…”

Section: Discussionmentioning

confidence: 71%

Preparation and evaluation of peptide-dendrimer-paclitaxel conjugates for treatment of heterogeneous stage 1 nonsmall cell lung cancer in 293T and L132 cell lines

Zhang¹,

Wang²,

Kan³

et al. 2017

Trop. J. Pharm Res

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Purpose: To develop peptide-dendrimer-paclitaxel conjugates for the treatment of heterogeneous stage 1 non small cell lung cancer (NSCLC) in 293T and L132cell line. Method: Dendrimer-paclitaxel conjugates (PAMAM-PTX) were prepared by NHS method and the conjugates were used for the synthesis of peptide-dendrimer-paclitaxel conjugates (GE-PAMAM-PTX). The particle sizes of PAMAM-PTX and GE-PAMAM-PTX were measured. Entrapment efficiency of PTX in PAMAM-PTX was measured while GE-PAMAM-PTX. PTX release from PAMAM-PTX and GE-PAMAM-PTX was determined using a dialysis bag in pH 7.4 phosphate buffer. The cytotoxicity of PAMAM-PTX, GE-PAMAM-PTX, PAMAM and PTX was evaluated by 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay using 293T cell lines. In vitro cellular uptake assay of PAMAM-PTX and GE-PAMAM-PTX and PTX at concentrations ranging from 0.01 to 0.5µM for 8 h was carried out in NSCLC cell lines 293T and L132. Results: More than 95 % entrapment efficiency of GE-PAMAM-PTX was observed with loading efficiency of 25 %. GE-PAMAM-PTX conjugates showed sustained release of PTX (~85 %) towards the end of 50 h. GE-PAMAM-PTX

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“…Such a technology can potentially advance precision medicine by helping identify the responders and nonresponders early on while minimizing adverse effects. Although the current study builds on the recent developments in theranostics, i.e., nanomaterials comprising of a cytotoxic payload and additionally tagged with a tracer allowed the spatial visualization of nanoparticles in vivo (56,57), such first-generation theranostic nanoparticles did not report on the efficacy of the nanoparticle-based treatment. The "always on" signal meant that these theranostic nanoparticles could not discriminate between a drug-sensitive and drug-resistant tumor.…”

Section: Discussionmentioning

confidence: 99%

Reporter nanoparticle that monitors its anticancer efficacy in real time

Kulkarni

Rao

Natarajan

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The ability to monitor the efficacy of an anticancer treatment in real time can have a critical effect on the outcome. Currently, clinical readouts of efficacy rely on indirect or anatomic measurements, which occur over prolonged time scales postchemotherapy or postimmunotherapy and may not be concordant with the actual effect. Here we describe the biology-inspired engineering of a simple 2-in-1 reporter nanoparticle that not only delivers a cytotoxic or an immunotherapy payload to the tumor but also reports back on the efficacy in real time. The reporter nanoparticles are engineered from a novel two-staged stimuli-responsive polymeric material with an optimal ratio of an enzyme-cleavable drug or immunotherapy (effector elements) and a drug function-activatable reporter element. The spatiotemporally constrained delivery of the effector and the reporter elements in a single nanoparticle produces maximum signal enhancement due to the availability of the reporter element in the same cell as the drug, thereby effectively capturing the temporal apoptosis process. Using chemotherapy-sensitive and chemotherapy-resistant tumors in vivo, we show that the reporter nanoparticles can provide a real-time noninvasive readout of tumor response to chemotherapy. The reporter nanoparticle can also monitor the efficacy of immune checkpoint inhibition in melanoma. The self-reporting capability, for the first time to our knowledge, captures an anticancer nanoparticle in action in vivo.T he failure of anticancer therapy is a major cause of mortality (1). Although the current dogma underlying resistance is based on the Darwinian selection of mutations acquired over time under chemotherapy pressure, emerging evidence indicates that anticancer drugs can be rendered ineffective early on by intrinsic or adaptive resistance as a function of tumor heterogeneity (2-4). For example, response rates to first-line chemotherapy treatments in metastatic breast cancer patients range from a dismal 30% to 70%, and patients with disease progression need to be switched to a different drug (5). Similarly, about 40-60% of patients with a wild-type KRAS do not respond to cetuximab (6). The ability to detect early whether a treatment is working or not and to switch, if necessary, to a regimen that is effective can have a significant effect on the outcome as well as quality of life (7,8).Currently, tumor response to therapy is determined using techniques for direct anatomical measurements, such as computed tomography (CT) and magnetic resonance imaging, or indirectly using positron emission tomography with 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG-PET) to quantify metabolic activity. However, these techniques lack the sensitivity or specificity to enable very early response assessment, and often, clinicopathological and metabolic readouts can be discordant (5, 9, 10). In the case of immunotherapy, for example, a productive immune response (T cell infiltration) and the unimpeded growth of the tumor will both be manifest as progression on the conventional ...

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Tumor-homing multifunctional nanoparticles for cancer theragnosis: Simultaneous diagnosis, drug delivery, and therapeutic monitoring

Cited by 324 publications

References 22 publications

Noninvasive Optical Imaging of Nanomedicine Biodistribution

Noninvasive Optical Imaging of Nanomedicine Biodistribution

Preparation and evaluation of peptide-dendrimer-paclitaxel conjugates for treatment of heterogeneous stage 1 nonsmall cell lung cancer in 293T and L132 cell lines

Reporter nanoparticle that monitors its anticancer efficacy in real time

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