Multifunctional nanomedicine platform for concurrent delivery of chemotherapeutic drugs and mild hyperthermia to ovarian cancer cells

Taratula, Olena; Dani, Raj Kumar; Schumann, Canan; Xu, Hong; Wang, Andrew; Song, Hyun-Ok; Dhagat, Pallavi

doi:10.1016/j.ijpharm.2013.09.032

Cited by 64 publications

(70 citation statements)

References 41 publications

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“…To attach a LHRH peptide to the graphene-dendrimer delivery system, the MAL group of the bifunctional PEG-chain was reacted with the thiol group of the cysteine in LHRH ( Figure 1C). 10,38 Coupling of the PEGylated complex with LHRH peptide was confirmed by BCA protein assay. 30 In addition, successful LOGr functionalization with Pc-PPIG4, followed by PEG and LHRH peptide modification was confirmed by Fourier transform infrared-attenuated total reflectance (FTIR-ATR) spectroscopy ( Figure S1).…”

mentioning

confidence: 96%

“…Unlike photosensitizers, PTT agents absorb the light, which is then transformed into heat and transferred to the intracellular environment, generating localized hyperthermia. [8][9][10][11] The combination of both PDT and PTT, which are based on different anticancer mechanisms, into a single therapeutic modality offers a highly proficient method to treat ovarian cancer tumors. To avoid multiple administrations of different therapeutic agents and improve patient compliance, it is highly desirable to have a single nanomedicine platform that possesses both the PDT and PTT therapeutic functions.…”

mentioning

confidence: 99%

“…The nearly neutral surface charge will lessen the interaction of the delivery system with macrophages and blood serum proteins during systemic circulation and reduce toxicity linked to cellular membrane damage. 10,30 To improve active intracellular uptake of the PEGylated complex, a cancer-targeting LHRH peptide was conjugated to the LOGr-Pc-PPIG4-PEG ( Figure 1C). The receptors for the LHRH peptide are overexpressed on the membranes of both primary and metastatic ovarian cancer cells, including the multidrug-resistant A2780/AD ovarian cancer cells used in this work, but are not evidently expressed in most healthy human tissue.…”

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confidence: 99%

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Phthalocyanine-loaded graphene nanoplatform for imaging-guided combinatorial phototherapy

Taratula¹,

Taratula²,

Patel³

et al. 2015

IJN

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We report a novel cancer-targeted nanomedicine platform for imaging and prospect for future treatment of unresected ovarian cancer tumors by intraoperative multimodal phototherapy. To develop the required theranostic system, novel low-oxygen graphene nanosheets were chemically modified with polypropylenimine dendrimers loaded with phthalocyanine (Pc) as a photosensitizer. Such a molecular design prevents fluorescence quenching of the Pc by graphene nanosheets, providing the possibility of fluorescence imaging. Furthermore, the developed nanoplatform was conjugated with poly(ethylene glycol), to improve biocompatibility, and with luteinizing hormone-releasing hormone (LHRH) peptide, for tumor-targeted delivery. Notably, a low-power near-infrared (NIR) irradiation of single wavelength was used for both heat generation by the graphene nanosheets (photothermal therapy [PTT]) and for reactive oxygen species (ROS)-production by Pc (photodynamic therapy [PDT]). The combinatorial phototherapy resulted in an enhanced destruction of ovarian cancer cells, with a killing efficacy of 90%–95% at low Pc and low-oxygen graphene dosages, presumably conferring cytotoxicity to the synergistic effects of generated ROS and mild hyperthermia. An animal study confirmed that Pc loaded into the nanoplatform can be employed as a NIR fluorescence agent for imaging-guided drug delivery. Hence, the newly developed Pc-graphene nanoplatform has the significant potential as an effective NIR theranostic probe for imaging and combinatorial phototherapy.

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confidence: 96%

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confidence: 99%

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confidence: 99%

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Phthalocyanine-loaded graphene nanoplatform for imaging-guided combinatorial phototherapy

Taratula¹,

Taratula²,

Patel³

et al. 2015

IJN

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“…37 Free-MTX could be internalized into cancer cells via folate receptors, 38 while PEG-PLDH-MTX nanoparticles could be limited by PEGylation. 39 LDH-MTX also showed similar cytotoxicity with PEG-PLDH-MTX ( Figure 5B and C), which was unexpected since LDH nanoparticles could hardly be internalized into cells in the presence of serum (Figure 4). However, the interlayer anions in LDH were exchangeable, 10 MTX intercalated into LDH may leak out and become internalized by the cells via folate receptor.…”

Section: Cell Viabilitymentioning

confidence: 70%

Improvement of pharmacokinetic and antitumor activity of layered double hydroxide nanoparticles by coating with PEGylated phospholipid membrane

Yan¹,

Zhang²,

Sheng-miao³

et al. 2014

IJN

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Layered double hydroxide (LDH) has attracted considerable attention as a drug carrier. However, because of its poor in vivo behavior, polyethylene glycolylated (PEGylated) phospholipid must be used as a coformer to produce self-assembled core–shell nanoparticles. In the present study, we prepared a PEGylated phospholipid-coated LDH (PLDH) (PEG-PLDH) delivery system. The PEG-PLDH nanoparticles had an average size of 133.2 nm. Their core–shell structure was confirmed by transmission electron microscopy and X-ray photoelectron spectroscopy. In vitro liposome-cell-association and cytotoxicity experiments demonstrated its ability to be internalized by cells. In vivo studies showed that PEGylated phospholipid membranes greatly reduced the blood clearance rate of LDH nanoparticles. PEG-PLDH nanoparticles demonstrated a good control of tumor growth and increased the survival rate of mice. These results suggest that PEG-PLDH nanoparticles can be a useful drug delivery system for cancer therapy.

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“…6 In other work, luteinizing hormone-releasing hormone (LHRH) peptide was used as an IONP-targeting moiety for ovarian cancer cells overexpressing the LHRH receptor. 12 Similarly, many ovarian cancers overexpress folate receptor alpha (FOLRα), 13,14 and this fact has been leveraged to selectively construction of Ffab and anti-botulinum toxin fab fragments…”

Section: Introductionmentioning

confidence: 99%

Antibody-mediated targeting of iron oxide nanoparticles to the folate receptor alpha increases tumor cell association in vitro and in vivo

Ndong¹,

Toraya-Brown²,

Kekalo³

et al. 2015

IJN

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Active molecular targeting has become an important aspect of nanoparticle development for oncology indications. Here, we describe molecular targeting of iron oxide nanoparticles (IONPs) to the folate receptor alpha (FOLRα) using an engineered antibody fragment (Ffab). Compared to control nanoparticles targeting the non-relevant botulinum toxin, the Ffab-IONP constructs selectively accumulated on FOLRα-overexpressing cancer cells in vitro, where they exhibited the capacity to internalize into intracellular vesicles. Similarly, Ffab-IONPs homed to FOLRα-positive tumors upon intraperitoneal administration in an orthotopic murine xenograft model of ovarian cancer, whereas negative control particles showed no detectable tumor accumulation. Interestingly, Ffab-IONPs built with custom 120 nm nanoparticles exhibited lower in vitro targeting efficiency when compared to those built with commercially sourced 180 nm nanoparticles. In vivo, however, the two Ffab-IONP platforms achieved equivalent tumor homing, although the smaller 120 nm IONPs were more prone to liver sequestration. Overall, the results show that Ffab-mediated targeting of IONPs yields specific, high-level accumulation within cancer cells, and this fact suggests that Ffab-IONPs could have future utility in ovarian cancer diagnostics and therapy.

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Multifunctional nanomedicine platform for concurrent delivery of chemotherapeutic drugs and mild hyperthermia to ovarian cancer cells

Cited by 64 publications

References 41 publications

Phthalocyanine-loaded graphene nanoplatform for imaging-guided combinatorial phototherapy

Phthalocyanine-loaded graphene nanoplatform for imaging-guided combinatorial phototherapy

Improvement of pharmacokinetic and antitumor activity of layered double hydroxide nanoparticles by coating with PEGylated phospholipid membrane

Antibody-mediated targeting of iron oxide nanoparticles to the folate receptor alpha increases tumor cell association in vitro and in vivo

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Multifunctional nanomedicine platform for concurrent delivery of chemotherapeutic drugs and mild hyperthermia to ovarian cancer cells

Cited by 64 publications

References 41 publications

Phthalocyanine-loaded graphene nanoplatform for&nbsp;imaging-guided combinatorial phototherapy

Phthalocyanine-loaded graphene nanoplatform for&nbsp;imaging-guided combinatorial phototherapy

Improvement of pharmacokinetic and antitumor activity of layered double hydroxide nanoparticles by coating with PEGylated phospholipid membrane

Antibody-mediated targeting of iron oxide nanoparticles to the folate receptor alpha increases tumor cell association in vitro and in vivo

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Phthalocyanine-loaded graphene nanoplatform for imaging-guided combinatorial phototherapy

Phthalocyanine-loaded graphene nanoplatform for imaging-guided combinatorial phototherapy