Multimodality treatment of cancer with herceptin conjugated, thermomagnetic iron oxides and docetaxel loaded nanoparticles of biodegradable polymers

Mi, Yu; Liu, Xiaoli; Zhao, Jing; Ding, Jun; Feng, Si‐Shen

doi:10.1016/j.biomaterials.2012.06.100

Cited by 112 publications

(77 citation statements)

References 43 publications

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“…For example, about 1.4 to 4-fold enhancement in internalization of 100 nm iron oxide nanoparticles has been reported in SK-BR-3 cells (30,31). Other studies have reported a 1.4-fold improvement in cytotoxicity of chitosan nanoparticles in an ovarian carcinoma continuous cell line, SKOV-3 (32); 1.2-1.3-fold enhancement in uptake of polylactic acid (PLA) or PLGA nanoparticles by SK-BR-3 cells (11,33,34); and 2-3-fold increase in uptake of albumin nanoparticles by BT-474 and SK-BR-3 cells (20).…”

Section: Discussionmentioning

confidence: 99%

Particle shape enhances specificity of antibody-displaying nanoparticles

Barua

Yoo

Kolhar

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

468

353

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Monoclonal antibodies are used in numerous therapeutic and diagnostic applications; however, their efficacy is contingent on specificity and avidity. Here, we show that presentation of antibodies on the surface of nonspherical particles enhances antibody specificity as well as avidity toward their targets. Using spherical, rod-, and disk-shaped polystyrene nano-and microparticles and trastuzumab as the targeting antibody, we studied specific and nonspecific uptake in three breast cancer cell lines: BT-474, SK-BR-3, and MDA-MB-231. Rods exhibited higher specific uptake and lower nonspecific uptake in all cells compared with spheres. This surprising interplay between particle shape and antibodies originates from the unique role of shape in determining binding and unbinding of particles to cell surface. In addition to exhibiting higher binding and internalization, trastuzumab-coated rods also exhibited greater inhibition of BT-474 breast cancer cell growth in vitro to a level that could not be attained by soluble forms of the antibody. The effect of trastuzumab-coated rods on cells was enhanced further by replacing polystyrene particles with pure chemotherapeutic drug nanoparticles of comparable dimensions made from camptothecin. Trastuzumab-coated camptothecin nanoparticles inhibited cell growth at a dose 1,000-fold lower than that required for comparable inhibition of growth using soluble trastuzumab and 10-fold lower than that using BSA-coated camptothecin. These results open unique opportunities for particulate forms of antibodies in therapeutics and diagnostics.morphology | nanomedicine | nanotechnology | drug delivery A ntibodies are used routinely in various analytical, diagnostic, and therapeutic applications, including cell and protein sorting (1), in vitro assays (2), in vivo imaging (3), and targeted delivery of therapeutics for the treatment of various diseases, including cancer (4), arthritis (5), and allergies (6). Significant attention has been given to understanding the molecular basis of antibody-antigen interactions (7) as well as to molecular engineering of antibodies to enhance their functions (8). An increasingly larger number of emerging applications of antibodies, however, are based on particulate systems in which antibodies are chemically or physically immobilized on the surface of microor nanoparticles (9-11). Such particulate antibodies are being pursued for targeted drug delivery or imaging. Although the benefits of antibodies in delivering therapeutic carriers to tissues have long been recognized, the effect of carriers themselves on antibody function has been relatively less studied. The function of antibodies that are immobilized on particles depends on the physicochemical properties of underlying particles, including the choice of material, size, surface modification, and shape. Commonly used nanoparticles for immobilizing antibodies include gold (9), iron oxide (12), quantum dots (13, 14), silica (15), polymers including poly(lactide-coglycolic acid) (PLGA) (11, 16) and polystyrene (...

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Section: Discussionmentioning

confidence: 99%

Particle shape enhances specificity of antibody-displaying nanoparticles

Barua

Yoo

Kolhar

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

468

353

View full text Add to dashboard Cite

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“…12,13 Recently, nanoparticle (NP)-based anticancer drug delivery systems, especially drug formulations with biodegradable polymeric NPs, have attracted considerable attention for their numerous advantages such as high cellular uptake, enhanced permeability and retention effect, and reduced cancer cell drug resistance. [14][15][16][17] Among the US Food and Drug Administration (FDA)-approved biodegradable polymers, poly(ε-caprolactone) (PCL) has gained considerable interest for drug delivery. However, its slow degradation rate and bad compatibility with soft tissues limit its application in nanomedicine.…”

Section: Introductionmentioning

confidence: 99%

Fabrication of genistein-loaded biodegradable TPGS-b-PCL nanoparticles for improved therapeutic effects in cervical cancer cells

Zhang¹,

Gan²,

Zeng³

et al. 2015

IJN

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Genistein is one of the most studied isoflavonoids with potential antitumor efficacy, but its poor water solubility limits its clinical application. Nanoparticles (NPs), especially biodegradable NPs, entrapping hydrophobic drugs have promising applications to improve the water solubility of hydrophobic drugs. In this work, TPGS- b -PCL copolymer was synthesized from ε-caprolactone initiated by d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) through ring-opening polymerization and characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, gel permeation chromatography, and thermogravimetric analysis. The genistein-loaded NPs were prepared by a modified nanoprecipitation method and characterized in the aspects of particle size, surface charge, morphology, drug loading and encapsulation efficiency, in vitro drug release, and physical state of the entrapped drug. The TPGS- b -PCL NPs were found to have higher cellular uptake efficiency than PCL NPs. MTT and colony formation experiments indicated that genistein-loaded TPGS- b -PCL NPs achieved the highest level of cytotoxicity and tumor cell growth inhibition compared with pristine genistein and genistein-loaded PCL NPs. Furthermore, compared with pristine genistein and genistein-loaded PCL NPs, the genistein-loaded TPGS- b -PCL NPs at the same dose were more effective in inhibiting tumor growth in the subcutaneous HeLa xenograft tumor model in BALB/c nude mice. In conclusion, the results suggested that genistein-loaded biodegradable TPGS- b -PCL nanoparticles could enhance the anticancer effect of genistein both in vitro and in vivo, and may serve as a potential candidate in treating cervical cancer.

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“…However, when administered in a suitable nanocarrier system, i.e., (P + S) mic , the antagonistic effects encountered reduced, as observed from the decrease in the IC50 value from 3.071 to 0.520 μg/mL. This phenomenon can be explained by our unique drug delivery system, where paclitaxel was released first then SAHA, which shows higher cytotoxicity compared to SAHA followed by paclitaxel release [57,58].…”

Section: Cytotoxicity Determinations For Various Drug/micelle Formulamentioning

confidence: 56%

Anti-migratory and increased cytotoxic effects of novel dual drug-loaded complex hybrid micelles in triple negative breast cancer cells

et al. 2015

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A polymer-based nanocarrier was developed for the co-delivery of epigenetic and chemotherapeutic drugs. The sterically stabilized hybrid micelle system uses micelles composed of D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS or TPGS) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000). In this study, suberoylanilide hydroxamic acid (SAHA) and paclitaxel were used as model drugs for combination chemotherapy to enhance therapeutic efficiency in targeting mesenchyme-like triple negative breast cancer (TNBC) cells. Combination therapy of paclitaxel and SAHA in a dual drug micelle system, (P + S) mic , exhibited an IC50 value of 0.52 μg/mL, which is about 5.91-fold more cytotoxic than the mere combination of free drugs (P + S). Furthermore, the (P + S) mic formulation was far more effective at inhibiting cell migration by more than 3.4-fold than the control. Thus, our findings show that the co-delivery of these drugs using the micelle system greatly enhances their therapeutic effect at a lower dosage, thereby minimizing toxicity. In addition, this formulation is proved to be remarkably effective in preventing cell migration at low dosage.

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Multimodality treatment of cancer with herceptin conjugated, thermomagnetic iron oxides and docetaxel loaded nanoparticles of biodegradable polymers

Cited by 112 publications

References 43 publications

Particle shape enhances specificity of antibody-displaying nanoparticles

Particle shape enhances specificity of antibody-displaying nanoparticles

Fabrication of genistein-loaded biodegradable TPGS-b-PCL nanoparticles for improved therapeutic effects in cervical cancer cells

Anti-migratory and increased cytotoxic effects of novel dual drug-loaded complex hybrid micelles in triple negative breast cancer cells

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