A facile preparation method of a PFC-containing nano-sized emulsion for theranostics of solid tumors

Shiraishi, Koji; Endoh, Reiko; Furuhata, Hiroshi; Nishihara, Masamichi; Suzuki, Ryo; Maruyama, Kazuo; Oda, Yusuke; Jo, Jun Ichiro; Tabata, Yasuhiko; Yamamoto, Jun; Yokoyama, Masayuki

doi:10.1016/j.ijpharm.2011.10.006

Cited by 36 publications

(36 citation statements)

References 45 publications

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“…Our results are supported by previously published reports showing that the number of fluorinated monomers plays a critical role in PFC loading and encapsulation by a polymeric shell. 11,25 For example, Yokoyama and co-workers synthesized a series of amphiphilic PEG-b-poly(fluoroheptyl aspartate) copolymers with a variable number of fluorinated alkyl chains and investigated their ability to encapsulate PFC forming nanodroplets. 11,25 Results showed that introducing 10% of fluoroheptyl units in the polymer backbone was sufficient to encapsulate the loaded PFP (45.5 mg/mL) forming nanodroplets.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…We did not evaluate the toxicity of the PFP given that it is commonly used in FDAapproved ultrasound contrast agents and its concentration in the blood circulation drops by 90% within 10 min of its administration. 25 …”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…The fluorinated and hydrophobic P(HDFMA-co-MMA) block is designed to facilitate the encapsulation of PFP in the droplets' core. 11,25 Histotripsy is a noninvasive, nonthermal, image-guided, ultrasound ablation method that uses extremely high acoustic pressure and microseconds long pulses to generate a cluster of microbubbles (bubble cloud) from pre-existing gas pockets in tissue. 12,26−29 Rapid expansion and energetic collapse (i.e., cavitation) of the formed microbubbles, each with an average diameter >50 μm, mechanically fragment the adjacent cells into subcellular debris.…”

Section: ■ Introductionmentioning

confidence: 99%

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Development of Nanodroplets for Histotripsy-Mediated Cell Ablation

Durmaz

Vlaisavljevich

et al. 2014

Mol. Pharmaceutics

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This report describes the synthesis of amphiphilic copolymers (ABC-1 and ABC-2) composed of a hydrophilic poly(ethylene glycol) (PEG) block, a central poly(acrylic acid) (PAA) block, and a random copolymer of heptadecafluorodecyl methacrylate (HDFMA) and methyl methacrylate (MMA) forming the hydrophobic block, which are used to form nanodroplets for ultrasound-mediated cell ablation. Specifically, the effect of molecular weight of PEG and P(HDFMA-co-MMA) blocks on polymer's ability to self-assemble around a variable amount (0%, 1%, and 2% v/v) of perfluoropentane (PFP) forming nanodroplets is investigated. The ability of different nanodroplets formulations embedded with a monolayer of red blood cells (RBCs) in tissue-mimicking agarose phantoms to initiate and sustain a bubble cloud in response to ultrasound treatments with different acoustic pressures and the associated ablation of RBCs were also investigated. Results show that ABC-1 polymer composed of a 2 kDa PEG block and a 6.7 kDa P(HDFMA-co-MMA) block better encapsulate the PFP core compared to ABC-2 polymer composed of a 5 kDa PEG block and 11.4 kDa P(HDFMA-co-MMA) block. Further, the ablative capacity indicated by the damage area in the RBCs monolayer increased with the increase in PFP content and reached its maximum with the nanodroplets formulated using ABC-1 polymer and encapsulating 2% v/v PFP. The nanodroplets formulated using ABC-1 polymer and loaded with 2% PFP produced the cavitation cloud and exhibited their ablative effect at an acoustic pressure that is 2.5-fold lower than the acoustic pressure needed to generate the same effect using a histotripsy (ultrasound) pulse alone, which indicates the ability of these nanodroplets to achieve targeted and self-limiting fractionation of disease cells while sparing neighboring healthy ones. Results also show that effective nanodroplets maintained their size and concentration upon incubation with bovine serum albumin at 37 °C for 24 h, which indicates their stability in physiologic conditions and their promise for in vivo cancer cell ablation.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

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Development of Nanodroplets for Histotripsy-Mediated Cell Ablation

Durmaz

Vlaisavljevich

et al. 2014

Mol. Pharmaceutics

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“…Temperature was measured after agitation using a needle type thermometer (Custom Co., Tokyo, Japan). Perfluoropropane content analysis was performed as reported previously [21]. The particle size and zeta potential of the liposomes and MBs were determined using a Zetasizer Nano ZS instrument (Malvern Instruments Ltd., Worcestershire, UK).…”

Section: Doxorubicin Liposome and Dlmbs Preparationmentioning

confidence: 99%

Evaluation of the potential of doxorubicin loaded microbubbles as a theranostic modality using a murine tumor model

et al. 2015

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In this study, a novel phospholipid-based microbubble formulation containing doxorubicin and perfluoropropane gas (DLMB) was developed. The DLMBs were prepared by mechanical agitation of a phospholipid dispersion in the presence of perfluoropropane (PFP)gas. An anionic phospholipid, distearoylphosphatidylglycerol (DSPG) was selected to load doxorubicin in the microbubbles by means of electrostatic interaction. The particle size, zeta potential, echogenicity and stability of the DLMBs were measured. Drug loading was ≥92%.The potential of the DLMBs for use as a theranostic modality were evaluated in tumor bearing mice. Gas chromatography analysis of PFP showed significant enhancement of PFP retention when doxorubicin was used at concentrations of 10-82% equivalent to DSPG. The inhibitory effects on the proliferation of B16BL6 melanoma murine cells in vitro were enhanced using a combination of ultrasound (US) irradiation and DLMBs. Moreover, in vivo DLMBs in combination with (US) irradiation significantly inhibited the growth of B16BL6 melanoma tumor in mice. Additionally, US echo imaging showed high contrast enhancement of the DLMBs in the tumor vasculature. These results suggest that DLMBs could serve as US triggered carriers of doxorubicin as well as tumor imaging agents in cancer therapy.

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“…121 Thus far, ultrasound has been largely investigated in combination with the nanoconstructs, as it allows for the safe and effective imaging of solid tumors as well as being capable of disrupting the nanoconstructs resulting in targeted drug release.…”

mentioning

confidence: 99%

Overview of the role of nanotechnological innovations in the detection and treatment of solid tumors

Frank¹,

Tyagi²,

Tomar³

et al. 2014

IJN

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Nanotechnology, although still in its infantile stages, has the potential to revolutionize the diagnosis, treatment, and monitoring of disease progression and success of therapy for numerous diseases and conditions, not least of which is cancer. As it is a leading cause of mortality worldwide, early cancer detection, as well as safe and efficacious therapeutic intervention, will be indispensable in improving the prognosis related to cancers and overall survival rate, as well as health-related quality of life of patients diagnosed with cancer. The development of a relatively new field of nanomedicine, which combines various domains and technologies including nanotechnology, medicine, biology, pharmacology, mathematics, physics, and chemistry, has yielded different approaches to addressing these challenges. Of particular relevance in cancer, nanosystems have shown appreciable success in the realm of diagnosis and treatment. Characteristics attributable to these systems on account of the nanoscale size range allow for individualization of therapy, passive targeting, the attachment of targeting moieties for more specific targeting, minimally invasive procedures, and real-time imaging and monitoring of in vivo processes. Furthermore, incorporation into nanosystems may have the potential to reintroduce into clinical practice drugs that are no longer used because of various shortfalls, as well as aid in the registration of new, potent drugs with suboptimal pharmacokinetic profiles. Research into the development of nanosystems for cancer diagnosis and therapy is thus a rapidly emerging and viable field of study.

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A facile preparation method of a PFC-containing nano-sized emulsion for theranostics of solid tumors

Cited by 36 publications

References 45 publications

Development of Nanodroplets for Histotripsy-Mediated Cell Ablation

Development of Nanodroplets for Histotripsy-Mediated Cell Ablation

Evaluation of the potential of doxorubicin loaded microbubbles as a theranostic modality using a murine tumor model

Overview of the role of nanotechnological innovations in the detection and treatment of solid tumors

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