Advances in an active and passive targeting to tumor and adipose tissues

Sakurai, Yasuhisa; Kajimoto, Kazuaki; Hatakeyama, Hiroto; Harashima, Hideyoshi

doi:10.1517/17425247.2015.955847

Cited by 48 publications

(39 citation statements)

References 104 publications

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“…[13][14][15] The potential of such drug delivery vehicles in biomedicine is illustrated by the fact that they not only prolong the circulation time of their payloads and protect them from premature degradation, but can also be actively or passively targeted to desired tissues and organs. 16 This results in an increase of the bioavailability of a drug and a reduction of side effects. In this context, the shape, size, and rigidity of nanoparticulate therapeutic agents play a key role in determining their uptake efficiency, circulation time, and distribution in the body.…”

Section: Introductionmentioning

confidence: 99%

Monodisperse Cylindrical Micelles and Block Comicelles of Controlled Length in Aqueous Media

et al. 2016

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Cylindrical block copolymer micelles have shown considerable promise in various fields of biomedical research. However, unlike spherical micelles and vesicles, control over their dimensions in biologically-relevant solvents has posed a key challenge that potentially limits in depth studies and their optimisation for applications. Here, we report the preparation of cylindrical micelles of length in the wide range of 40 nm -1.10 µm in aqueous media with narrow length distributions (length polydispersities < 1.10). In our approach, an amphiphilic linear-brush block copolymer, with high potential for functionalization, was synthesized based on poly(ferrocenyldimethylsilane)-b-poly(allyl glycidyl ether) (PFS-b-PAGE) decorated with triethylene glycol (TEG), abbreviated as PFS-b-(PEO-g-TEG). PFS-b-(PEO-g-TEG) cylindrical micelles of controlled length with low polydispersities were prepared in N,N-dimethylformamide using small seed initiators via living crystallization-driven self-assembly. Successful dispersion of these micelles into aqueous media was achieved by dialysis against deionized water. Furthermore, B-A-B amphiphilic triblock comicelles with PFS-b-poly(2-vinylpyridine) (P2VP) as hydrophobic "B" blocks and hydrophilic PFS-b-(PEO-g-TEG) "A" segments were prepared and their hierarchical self-assembly in aqueous media studied. It was found that superstructures formed depend on the length of the hydrophobic blocks. Quaternization of P2VP was shown to cause the disassembly of the superstructures, resulting in the first examples of water-soluble cylindrical multi-block comicelles. We also demonstrate the ability of the triblock comicelles with quaternized terminal segments to complex DNA and, thus, to potentially function as gene vectors.

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Section: Introductionmentioning

confidence: 99%

Monodisperse Cylindrical Micelles and Block Comicelles of Controlled Length in Aqueous Media

et al. 2016

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“…However, margination is not limited to WBCs and has been observed for other particles as well (2). This has sparked a lot of interest because of its potential applications in relation to cancer therapy (3)(4)(5)(6)(7). Tumor sites are generally characterized by 1) leaky vasculature, which allows drugcarrying particles to diffuse into them, and 2) a lack of lymphatics, which allows these particles to remain inside the tumor.…”

Section: Introductionmentioning

confidence: 99%

Direct Tracking of Particles and Quantification of Margination in Blood Flow

Carboni

Bognet

Bouchillon

et al. 2016

Biophysical Journal

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Margination refers to the migration of particles toward blood vessel walls during blood flow. Understanding the mechanisms that lead to margination will aid in tailoring the attributes of drug-carrying particles for effective drug delivery. Most previous studies evaluated the margination propensity of these particles via an adhesion mechanism, i.e., by measuring the number of particles that adhered to the channel wall. Although particle adhesion and margination are related, adhesion also depends on other factors. In this study, we quantified the margination propensity of particles of varying diameters (0.53, 0.84, and 2.11 mm) and apparent wall shear rates (30, 61, and 121 s À1 ) by directly tracking fluorescent particles flowing through a microfluidic channel. The margination parameter, M, is defined as the total number of particles found within the cell-free layers normalized by the total number of particles that passed through the channel. In this study, an M-value of 0.2 indicated no margination, which was observed for all particle sizes in water. In the case of blood, larger particles were found to have higher M-values and thus marginated more effectively than smaller particles. The corresponding M-values at the device outlet were 0.203, 0.223, and 0.285 for 0.53-, 0.84-, and 2.11-mm particles, respectively. At the inlet, the M-values for all particle sizes in blood were <0.2, suggesting that non-fully-developed flow and constriction may lead to demargination. For particle velocities transverse to the flow direction (v y ), all particle sizes showed a larger standard deviation of v y as well as a higher effective diffusivity when the particles were suspended in blood relative to water. These higher values are attributed to collisions between the blood cells and particles, further supporting recent simulation results. In terms of flow rates, for a given particle size, the higher the flow rate, the higher the M-value.

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“…As soon as the conjugate is internalized into the tumour cell, the DDS must quickly release the cytotoxic drug to be effective. Similarly, the radiopharmaceutical linked to the tumour cell must be given adequate time for the DDS to emit the radiation dose and image the tumour cells [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

“…The accumulation of macromolecules, including plasma proteins, does not require a specific receptor. Therefore, the mechanism of EPR probably acts as a passive transport system within the cells [1][2][3].…”

Section: Introductionmentioning

confidence: 99%