DNA Nanoparticles and Development of DNA Delivery Vehicles for Gene Therapy

Vijayanathan, Veena; Thomas, Thresia

doi:10.1021/bi0203987

Cited by 345 publications

(298 citation statements)

References 129 publications

(221 reference statements)

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“…acids and small molecule drugs because of their significantly different physico-chemical properties [184]. Attempts to develop nanocarriers for co-delivery of small interfering RNA (siRNA) and small molecule drugs continue to grow, particularly in recent years [185].…”

Section: Combined Gene and Chemotherapymentioning

confidence: 99%

“Combo” nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy

Kemp

Shim

Heo

et al. 2016

Advanced Drug Delivery Reviews

440

258

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a b s t r a c t a r t i c l e i n f oThe dynamic and versatile nature of diseases such as cancer has been a pivotal challenge for developing efficient and safe therapies. Cancer treatments using a single therapeutic agent often result in limited clinical outcomes due to tumor heterogeneity and drug resistance. Combination therapies using multiple therapeutic modalities can synergistically elevate anti-cancer activity while lowering doses of each agent, hence, reducing side effects. Co-administration of multiple therapeutic agents requires a delivery platform that can normalize pharmacokinetics and pharmacodynamics of the agents, prolong circulation, selectively accumulate, specifically bind to the target, and enable controlled release in target site. Nanomaterials, such as polymeric nanoparticles, gold nanoparticles/cages/shells, and carbon nanomaterials, have the desired properties, and they can mediate therapeutic effects different from those generated by small molecule drugs (e.g., gene therapy, photothermal therapy, photodynamic therapy, and radiotherapy). This review aims to provide an overview of developing multi-modal therapies using nanomaterials ("combo" nanomedicine) along with the rationale, up-to-date progress, further considerations, and the crucial roles of interdisciplinary approaches.

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Section: Combined Gene and Chemotherapymentioning

confidence: 99%

“Combo” nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy

Kemp

Shim

Heo

et al. 2016

Advanced Drug Delivery Reviews

440

258

View full text Add to dashboard Cite

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“…Compactification of DNA into ϳ100-nm large complexes with oppositely charged proteins and polycations is an important tool in gene therapy 1 to deliver DNA into an infected cell. 2 In particular, DNA condensates with polylysine 3,4 and polyamines 5,6 are used for these purposes.…”

Section: Introductionmentioning

confidence: 99%

Complexation of semiflexible chains with oppositely charged cylinder

Cherstvy

Winkler

2004

The Journal of Chemical Physics

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We study the complexation of long thin semiflexible polymer chains with an oppositely charged cylinder. Starting from the linear Poisson-Boltzmann equation, we calculate the electrostatic potential and the energy of such a charge distribution. We find that sufficiently flexible chains prefer to wrap around the cylinder in a helical manner, when their charge density is smaller than that of the cylinder. The optimal value of the helical pitch is found by minimization of the sum of electrostatic and bending energies. The dependence of the pitch on the number of chains, their rigidity, and salt concentration in solution is analyzed. We discuss our results in the light of recent experiments on DNA complexation with cylindrical dendronized polymers.

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“…This precipitate subsequently redissolves if the concentration is increased beyond a second critical value. These phenomena, jointly referred to as reentrant condensation [6], have attracted considerable attention because they are a fundamental and generic aspect of polyelectrolyte behavior, with potential relevance for the understanding and development of biological phenomena and applications such as gene delivery [7]. Under dilute conditions, the formation and redissolution of multimolecular aggregates are replaced by, respectively, single-chain "collapse" and reexpansion.…”

mentioning

confidence: 99%

Salt-Induced Collapse and Reexpansion of Highly Charged Flexible Polyelectrolytes

2006

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We study the salt-dependent conformations of dilute flexible polyelectrolytes in solution via computer simulations. Low concentrations of multivalent salt induce the known conformational collapse of individual polyelectrolyte chains, but as the salt concentration is increased further this is followed by a reexpansion. We explicitly demonstrate that multivalent counterions can overcompensate the bare charge of the chain in the reexpansion regime. Both the degree of reexpansion and the occurrence of overcharging sensitively depend on ion size. Our findings are relevant for a wide range of salt-induced complexation phenomena.PACS numbers: 82.35. Rs, 36.20.Ey, 87.15.He, 87.15.Aa Many biological and synthetic polyelectrolytes undergo two macroscopic phase transitions upon addition of multivalent salt or charged small molecules [1,2,3,4,5]. First, precipitation of polyelectrolytes occurs if the concentration of the added salt exceeds a critical value. This precipitate subsequently redissolves if the concentration is increased beyond a second critical value. These phenomena, jointly referred to as reentrant condensation [6], have attracted considerable attention because they are a fundamental and generic aspect of polyelectrolyte behavior, with potential relevance for the understanding and development of biological phenomena and applications such as gene delivery [7]. Under dilute conditions, the formation and redissolution of multimolecular aggregates are replaced by, respectively, single-chain "collapse" and reexpansion. This behavior is directly observed in, e.g., the stretching of individual DNA coils in salty solution [8].Whereas several theoretical explanations for reentrant condensation have been proposed [6,9,10,11], important open questions remain regarding the suggested mechanisms, and several predictions have only partially been verified. Two main scenarios can be distinguished.(1) Charge inversion: Counterions form a strongly correlated liquid at the polyelectrolyte surface and, at high salt concentration, overcompensate the bare chain charge. Condensation of a polyelectrolyte is predicted to take place if its effective charge is close to zero [6,12]. (2) The two-state model [9] explains precipitation and redissolution of flexible polyelectrolytes by assuming that individual chains adopt either a collapsed or an extended state. This scenario predicts a strong sensitivity to ion size, which is not considered in Refs. [6,12]. In addition, in this case overcharging does not occur by necessity, but may be mitigated by coion association [11].Computer simulations offer the possibility to study this behavior at a microscopic level, but hitherto most simulations of flexible chains have focused on solutions with only divalent salt [13,14] or no salt at all [15,16,17,18]. Whereas chain collapse has been observed under the influence of divalent salt or counterions [16], the reexpansion observed in experiments and predicted by theory has not been reproduced in computer simulations. In this Letter, we aim to clarify ...

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DNA Nanoparticles and Development of DNA Delivery Vehicles for Gene Therapy

Cited by 345 publications

References 129 publications

“Combo” nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy

“Combo” nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy

Complexation of semiflexible chains with oppositely charged cylinder

Salt-Induced Collapse and Reexpansion of Highly Charged Flexible Polyelectrolytes

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