Targeted Nanoparticulate drug-delivery Systems for Treatment of Solid Tumors: a Review

Bhattacharjee, Himanshu; Balabathula, Pavan; Wood, George C.

doi:10.4155/tde.10.47

Cited by 25 publications

(11 citation statements)

References 130 publications

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“…2 Although a number of novel anticancer drugs have been developed, the use of existing drugs such as doxorubicin (Dox), paclitaxel and cisplatin are still predominant in the clinic. 3 More specifically, anthracycline drugs such as Dox are considered one of the most effective anticancer drugs ever developed. 4 It has been shown that Dox induces caspase-dependent apoptosis in cancer cells due to oxidative DNA damage in addition to topoisomerase II inhibition.…”

Section: Introductionmentioning

confidence: 99%

Anti-cancer activity of doxorubicin-loaded liposomes co-modified with transferrin and folic acid

Sriraman

Salzano

Sarısözen

et al. 2016

European Journal of Pharmaceutics and Biopharmaceutics

102

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Cancer-specific drug delivery represents an attractive approach to prevent undesirable side-effects and increase the accumulation of the drug in the tumor. Surface modification of nanoparticles such as liposomes with targeting moieties specific to the up-regulated receptors on the surface of tumor cells thus represents an effective strategy. Furthermore, since this receptor expression can be heterogeneous, using a dual-combination of targeting moieties may prove advantageous. With this in mind, the anti-cancer activity of PEGylated doxorubicin-loaded liposomes targeted with folic acid (F), transferrin (Tf) or both (F+Tf) was evaluated. The dual-targeted liposomes showed a 7-fold increase in cell association compared to either of the single-ligand targeted ones in human cervical carcinoma (HeLa) cell monolayers. The increased penetration and cell association of the dual-targeted liposomes was also demonstrated using HeLa cell spheroids. The in vitro cytotoxicity of the doxorubicin liposomes (LD) was then evaluated using HeLa and A2780-ADR ovarian carcinoma cell monolayers. In both these cell lines, the (F+Tf) LD showed significantly higher cytotoxic effects than the untargeted, or single-ligand targeted liposomes. Ina HeLa xenograft model in nude mice, compared to the untreated group, though the untargeted LD showed 42% tumor growth inhibition, both the (F) LD as well as (F+Tf) LD showed 75% and 79% tumor growth inhibition respectively. These results thus highlight that though the dual-targeted liposomes represent an effective cytotoxic formulation in the in vitro setting, they were equally effective as the folic acid-targeted liposomes in reducing tumor burden in the more complex in vivo setting in this particular model.

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Section: Introductionmentioning

confidence: 99%

Anti-cancer activity of doxorubicin-loaded liposomes co-modified with transferrin and folic acid

Sriraman

Salzano

Sarısözen

et al. 2016

European Journal of Pharmaceutics and Biopharmaceutics

102

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“…The drug biodistribution can be suitably altered and side effects can be minimized by employing targeted delivery systems. A wide variety of drug carriers and passive and active targeting strategies have been reported in the literature 1 . However, upon reaching the intended site, the rate of drug release from the carriers is often very slow.…”

Section: Introductionmentioning

confidence: 99%

Polymer-Coated Echogenic Lipid Nanoparticles with Dual Release Triggers

Nahire¹,

Haldar²,

Paul

et al. 2013

Biomacromolecules

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Although lipid nanoparticles are promising drug delivery vehicles, passive release of encapsulated contents at the target site is often slow. Herein, we report contents release from targeted, polymer coated, echogenic lipid nanoparticles in the cell cytoplasm by redox trigger and simultaneously enhanced by diagnostic frequency ultrasound. The lipid nanoparticles were polymerized on the external leaflet using a disulfide cross-linker. In the presence of cytosolic concentrations of glutathione, the lipid nanoparticles released 76% of encapsulated contents. Plasma concentrations of glutathione failed to release the encapsulated contents. Application of 3 MHz ultrasound for 2 minutes simultaneously with the reducing agent enhanced the release to 96%. Folic acid conjugated, doxorubicin loaded nanoparticles showed enhanced uptake and higher cytotoxicity in cancer cells overexpressing the folate receptor (compared to the control). With further developments, these lipid nanoparticles have the potential to be used as multimodal nanocarriers for simultaneous targeted drug delivery and ultrasound imaging.

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“…Nanodevices can be rationally designed to tailor functionality for a specific application. [15][16][17] Importantly, nanoparticles have been found to preferentially target phagocytic innate immune cells, 18,19 which makes them a compelling new generation of therapeutic agents to modulate inflammatory responses in specific tissues/organs. [11][12][13][14] Nanoparticles can also optimize therapeutic outcomes by improving in vivo biodistribution, achieving tissue/cell targeting, and sustaining the release of drugs.…”

mentioning

confidence: 99%

Amino Acid-Dependent Attenuation of Toll-like Receptor Signaling by Peptide-Gold Nanoparticle Hybrids

Yang

Fung

et al. 2015

ACS Nano

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Manipulation of immune responsiveness using nanodevices provides a potential approach to treat human diseases. Toll-like receptor (TLR) signaling plays a central role in the pathophysiology of many acute and chronic human inflammatory diseases, and pharmacological regulation of TLR responses is anticipated to be beneficial in many of these inflammatory conditions. Here we describe the discovery of a unique class of peptide-gold nanoparticle hybrids that exhibit a broad inhibitory activity on TLR signaling, inhibiting signaling through TLRs 2, 3, 4, and 5. As exemplified using TLR4, the nanoparticles were found to inhibit both arms of TLR4 signaling cascade triggered by the prototypical ligand, lipopolysaccharide (LPS). Through structure-activity relationship studies, we identified the key chemical components of the hybrids that contribute to their immunomodulatory activity. Specifically, the hydrophobicity and aromatic ring structure of the amino acids on the peptides were essential for modulating TLR4 responses. This work enhances our fundamental understanding of the role of nanoparticle surface chemistry in regulating innate immune signaling, and identifies specific nanoparticle hybrids that may represent a unique class of anti-inflammatory therapeutics for human inflammatory diseases.

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Targeted Nanoparticulate drug-delivery Systems for Treatment of Solid Tumors: a Review

Cited by 25 publications

References 130 publications

Anti-cancer activity of doxorubicin-loaded liposomes co-modified with transferrin and folic acid

Anti-cancer activity of doxorubicin-loaded liposomes co-modified with transferrin and folic acid

Polymer-Coated Echogenic Lipid Nanoparticles with Dual Release Triggers

Amino Acid-Dependent Attenuation of Toll-like Receptor Signaling by Peptide-Gold Nanoparticle Hybrids

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