Tumor targeting using polyamidoamine dendrimer–cisplatin nanoparticles functionalized with diglycolamic acid and herceptin

Kesavan, Akila; Ilaiyaraja, P.; Beaula, Winfred Sofi; Kumari, Vuttaradhi Veena; Lal, Jawahar; Arunkumar, Chellaiah; Anjana, G.; Srinivas, Satish; Ramesh, Anita; Rayala, Suresh K.; Ponraju, D.; Venkatraman, Ganesh

doi:10.1016/j.ejpb.2015.08.001

Cited by 44 publications

(20 citation statements)

References 24 publications

(11 reference statements)

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“…2 a). The synthesis procedure included extensive washing, of the derivatized dendrimer with water, and centrifugation with Microcon ® (cutoff of 10 kDa) in order to remove un-reacted FITC [ 33 – 37 ]. According to the structure of the intermediate PAMAM G4.5- N -Boc-piperazinyl, it was anticipated that only two units of FITC had been incorporated.…”

Section: Resultsmentioning

confidence: 99%

“…The mixture was purified by gel filtration and fractions of 500 μL were collected and controlled by TLC. The fractions 5–9 were joined and non-covalently bound FITC to the dendrimers was eliminated by three cycles of washing with distilled water and centrifugation with a centrifugal filter (cutoff of 10 KDa, Microcon ® ) (at 12,000 rpm by 10 min) [ 33 – 37 ]. Finally, the obtained supernatant was lyophilized.…”

Section: Methodsmentioning

confidence: 99%

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In vitro and in vivo uptake studies of PAMAM G4.5 dendrimers in breast cancer

Oddone

Lecot²,

Fernández³

et al. 2016

J Nanobiotechnol

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BackgroundBreast cancer is the second leading cause of cancer death worldwide. Nanotechnology approaches can overcome the side effects of chemotherapy as well as improve the efficacy of drugs. Dendrimers are nanometric size polymers which are suitable as drug delivery systems. To the best of our knowledge, studies on the application of PAMAM G4.5 (polyamidoamine half generation 4) dendrimers as potential drug delivery systems in breast cancer have not been reported. In this work we developed a PAMAM G4.5 dendrimer containing FITC (fluorescein isothiocyanate) dye to study their uptake by murine breast cancer cells and BALB/c mice breast tumors.ResultsWe performed a reaction between FITC and PAMAM G4.5 dendrimers which were previously derivatized with piperazine (linker molecule), characterized them by 1H NMR (proton nuclear magnetic resonance) spectroscopy and MALDI-TOF (matrix-assisted laser desorption/ionization- time-of-flight) mass spectrometry. The experimental data indicated that 2 FITC molecules could be bound covalently at the PAMAM G4.5 dendrimer surface, with 17 FITC molecules probably occluded in PAMAM dendrimers cavity. PAMAM-FITC dendrimer (PAMAM G4.5-piperazinyl-FITC dendrimer) size distribution was evaluated by DLS (dynamic light scattering) and TEM (transmission electron microscopy). The nanoparticle hydrodynamic size was 96.3 ± 1.4 nm with a PdI (polydispersion index) of 0.0296 ± 0.0171, and the size distribution measured by TEM was 44.2 ± 9.2 nm. PAMAM-FITC dendrimers were neither cytotoxic in 4T1 cells nor hemolytic up to 24 h of incubation. In addition, they were uptaken in vitro by 4T1 cells and in vivo by BALB/c mice breast tumors. PAMAM G4.5-piperazinyl-FITC dendrimer intracellular distribution was observed through histologic analysis of the tumor by laser confocal microscopy.ConclusionThese results indicate that PAMAM G4.5 dendrimers enter tumor tissue cells, being good candidates to be used as antitumor drug delivery systems for breast cancer treatment and diagnosis.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

In vitro and in vivo uptake studies of PAMAM G4.5 dendrimers in breast cancer

Oddone

Lecot²,

Fernández³

et al. 2016

J Nanobiotechnol

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“…This dendrimer-based formulation entered the nucleus and damaged nuclear fragmentation by inducing cell death via apoptosis. These nanoparticles are entered via receptor-mediated endocytosis [51]. This work reported a synthesis of pegylated polyamidoamine (PAMAM) dendrimer-loaded with cisplatin (CDDP) and fluorouracil (5-FU).…”

Section: Dendrimersmentioning

confidence: 99%

Recent progress in nanotechnology-based novel drug delivery systems in designing of cisplatin for cancer therapy: an overview

Farooq

Aquib

Farooq

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

107

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2019) Recent progress in nanotechnology-based novel drug delivery systems in designing of cisplatin for cancer therapy: an overview, Artificial ABSTRACT Cisplatin cis-(diammine)dichloridoplatinum(II) (CDDP) is the first platinum-based complex approved by the food and drug administration (FDA) of the United States (US). Cisplatin is the first line chemotherapeutic agent used alone or combined with radiations or other anti-cancer agents for a broad range of cancers such as lung, head and neck. Aroplatin TM , Lipoplatin TM and SPI-077 are PEGylated liposomebased nano-formulations that are still under clinical trials. They have many limitations, for example, poor aqueous solubility, drug resistance and toxicities, which can be overcome by encapsulating the cisplatin in Nemours nanocarriers. The extensive literature from different electronic databases covers the different nano-delivery systems that are developed for cisplatin. This review critically emphasizes on the recent advancement, development, innovations and updated literature reported for different carrier systems for CDDP. ARTICLE HISTORY Current status of FDA-approved/under clinical trials CDDP nano-formulationsMany liposomal-based nano-formulations are at the stage of clinical trials. One of under clinical trials drugs, Lipoplatin (Regulon, Inc.), is liposome-based platinum formulation under Phase III clinical trials [11]. It contains a combination of cisplatin (9%) and lipids (91%(w/w)), including soy phosphatidylcholine (SPC-3), cholesterol, dipalmitoyl phosphatidyl glycerol (DPPG) and methoxy-PEG-distearoyl phosphatidyl

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“…Kesavan et al prepared a herceptin and diglycolamic acid (DGA) functionalized polyamidoamine (PAMAM) dendrimer for cisplatin delivery (herceptin‐DGA‐G4‐cisplatin). Herceptin‐DGA‐G4‐cisplatin demonstrated increased cellular uptake and accumulation than untargeted DGA‐G4‐cisplatin and free cisplatin, leading to improved S‐phase arrest, enhanced apoptosis, as well as more effective tumor regression in vivo …”

Section: Targeted Deliverymentioning

confidence: 99%

Multifunctional platinum‐based nanoparticles for biomedical applications

Cheng

Liu

2016

WIREs Nanomed Nanobiotechnol

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Platinum-based anticancer drugs play a central role in current cancer therapy. However, their applicability and efficacy are limited by drug resistance and adverse effects. Nanocarrier-based platinum drug delivery systems are promising alternatives to circumvent the disadvantages of bare platinum drugs. The various properties of nanoparticle chemistry allow for the trend toward multiple functionality. Nanoparticles preferentially accumulate at the tumor site through passive targeting, and the attachment of tumor targeting moieties further enhances their tumor-specific localization as well as tumor cell uptake. The introduction of stimuli-responsive groups into drug delivery systems can further achieve spatially and temporally controlled drug release in response to specific stimuli. Combination therapy strategies have been used to promote synergetic efficacy and overcome the resistance of platinum drugs. The tumor-localized drug delivery strategies exhibit benefits for preventing local tumor recurrence. In addition, the combination of platinum drugs and imaging agents in one unity allows the cancer diagnostics for real-time monitoring the distribution of drug-loaded nanoparticles inside the body and tumor. This review discusses recent scientific advances in multifunctional nanoparticle formulations of platinum drugs, and these designs exhibit new potential of multifunctional nanoparticles for delivering platinum-based anticancer drugs. WIREs Nanomed Nanobiotechnol 2017, 9:e1410. doi: 10.1002/wnan.1410 For further resources related to this article, please visit the WIREs website.

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Tumor targeting using polyamidoamine dendrimer–cisplatin nanoparticles functionalized with diglycolamic acid and herceptin

Cited by 44 publications

References 24 publications

In vitro and in vivo uptake studies of PAMAM G4.5 dendrimers in breast cancer

In vitro and in vivo uptake studies of PAMAM G4.5 dendrimers in breast cancer

Recent progress in nanotechnology-based novel drug delivery systems in designing of cisplatin for cancer therapy: an overview

Multifunctional platinum‐based nanoparticles for biomedical applications

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