Nanoparticle-assisted Combination Therapies for Effective Cancer Treatment

Hu, Che Ming Jack; Aryal, Santosh; Zhang, Liangfang

doi:10.4155/tde.10.13

Cited by 512 publications

(348 citation statements)

References 69 publications

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“…showing that combined polymersome-delivered therapy is much better than single drug encapsulated therapy. The effect of combinational therapy, delivered via nanoparticles, has been extensively reviewed and current evidence shows that this combinational therapy is highly dependent on the molar ratios of drugs and the sequence in which they are delivered 43 . In support of this, we observed that the cytotoxicity of dual loaded polymersomes is greater than polymersomes loaded with a single drug.…”

Section: Cellular Internalisation Kineticsmentioning

confidence: 99%

Polymersome-Mediated Delivery of Combination Anticancer Therapy to Head and Neck Cancer Cells: 2D and 3D in Vitro Evaluation

et al. 2014

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Polymersomes have the potential to encapsulate and deliver chemotherapeutic drugs into tumour cells, reducing off-target toxicity that often compromises anti-cancer treatment. Here we assess the ability of the pH-sensitive poly 2-(methacryloyloxy)ethyl phosphorylcholine (PMPC)-poly 2-(diisopropylamino)ethyl methacrylate (PDPA) polymersomes to encapsulate chemotherapeutic agents for effective combinational anti-cancer therapy. Polymersome uptake and ability to deliver encapsulated drugs into healthy normal oral cells and oral head and neck squamous cell carcinoma (HNSCC) cells was measured in two and three-dimensional culture systems. PMPC-PDPA polymersomes were more rapidly internalised by HNSCC cells compared to normal oral cells. Polymersome cellular up-take was found to be mediated by class B scavenger receptors.We also observed that these receptors are more highly expressed by cancer cells compared to normal oral cells, enabling polymersome-mediated targeting. Doxorubicin and paclitaxel were encapsulated into pH-sensitive PMPC-PDPA polymersomes with high efficiencies either in isolation or as a dual-load for both singular and combinational delivery. In monolayer culture, only a short exposure to drug-loaded polymersomes was required to elicit a strong cytotoxic effect. When delivered to three-dimensional tumour models, PMPC-PDPA polymersomes were able to penetrate deep into the centre of the spheroid resulting in extensive cell damage when loaded with both singular and dual-loaded chemotherapeutics. PMPC-PDPA polymersomes offer a novel system for the effective delivery of chemotherapeutics for the treatment of HNSCC.Moreover, the preferential internalisation of PMPC polymersomes by exploiting elevated scavenger receptor expression on cancer cells opens up the opportunity to target polymersomes to tumours.3

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Section: Cellular Internalisation Kineticsmentioning

confidence: 99%

Polymersome-Mediated Delivery of Combination Anticancer Therapy to Head and Neck Cancer Cells: 2D and 3D in Vitro Evaluation

et al. 2014

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“…Current aggressive multidisciplinary advances in improving the efficacy of cancer therapeutics are due to combination of these two dynamic research fields (Mollazade et al, 2013). There are also some challenges and design specifications that need to be addressed in optimizing nanoparticle-based combination chemotherapy (Kalaria et al, 2009;Guhagarkar et al, 2010;Hu et al, 2010;Benival and PV, 2012;Jain et al, 2012;Deng and Zhang, 2013;Duong and Yung, 2013;Liboiron and Mayer 2014;Salehi et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

DOX-MTX-NPs Augment p53 mRNA Expression in OSCC Model in Rat: Effects of IV and Oral Routes

Abbasi¹,

Khiavi²,

Amir³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy worldwide. Cancer development and progression require inactivation of tumor suppressor genes and activation of proto-oncogenes. The well recognized mechanism of action demonstrated for chemotherapeutic agents is induction of apoptosis via reactivation of p53. In this context, we evaluate the efficacy of IV and oral routes of our novel PH and temperature sensitive doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NP) in affecting p53 profile in an OSCC rat model. Methods: In this study, 120 male rats were divided into 8 groups of 15 animals each. The new formulated DOX-MTX NP and free doxorubicin were IV and orally given to rats with 4-nitroquinoline-1-oxide induced OSCC. Results: Results showed that both DOX and DOX-MTX-NP caused significant increase in mRNA levels of P53 compared to the untreated group (p<0.000). With both DOX and DOX-MTX NP, the IV mode was more effective than the oral (gavage) route (p<0.000). Surprisingly, in oral mode, p53 mRNA was not affected in DOX treated groups (p>0.05), Nonetheless, both IV and oral administration of MTX-DOX NP showed superior activity (~3 fold) over free DOX in reactivation of p53 in OSCC (p<0.000). The effectiveness of oral route in group treated with nanodrug accounts for the enhanced bioavailability of nanoparticulated DOX-MTX compared to free DOX. Moreover, in treated groups, tumor stage was markedly related to the amount of p53 mRNA (p<0.05). Conclusion: Both oral and IV application of our novel nanodrug possesses superior activity over free DOX-in up-regulation of p53 in a OSCC model and this increase in p53 level associated with less aggressive tumors in our study. Although, impressive results obtained with IV form of nanodrug (-21 fold increase in p53 mRNA level) but both forms of nanodrug are effective in OSCC, with less toxicity normal cells.

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“…Hence, combination therapy uses combined regimes that multiply the additive effects to the targeted cancer cells (Tacar et al, 2013). Afterwards, when synergistic combination with enhanced therapeutic effects get combined with an appropriate nanodelivery system such as the nanoparticles, a much powerful anticancer weapon create that could efficiently and specifically target tumoral cells (Yoo and Park, 2004;Hu et al, 2010;Wang et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Combination chemotherapy and nanoparticle drug delivery put forwards significant promise in cancer treatment. Concomitant use of two or more drugs results in additive\synergic cytotoxic on cancer cells and can overcome drug resistance through distinct mechanisms of action (Hu et al, 2010;Rossi et al, 2010). On the other side, nanoparticle drug delivery enhances therapeutic effectiveness whilst reduces toxicity on healthy cells through improving their pharmacokinetics.…”

Section: New Formulated "Dox-mtx-loaded Nanoparticles" Downregulate Hmentioning

confidence: 99%

New formulated "DOX-MTX-loaded Nanoparticles" Down-regulate HER2 Gene Expression and Improve the Clinical Outcome in OSCCs Model in Rat: the Effect of IV and Oral Modalities

Abbasi

Amir²,

Hamishehkar³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: Oral squamous cell carcinoma (OSCC) remains as one of the most difficult malignancies to control because of its high propensity for local invasion and cervical lymph node dissemination. In this study, we evaluate the efficacy of our novel pH and temperature sensitive doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NP) in affecting HER2 expression profile in OSCC model in rat. Results: DOX-MTX-nanoparticle complexes caused significant decrease in mRNA level of HER2 compared to untreated cancers (p<0.05) and this finding was more pronounced with the IV mode (p<0.000). Surprisingly, HER2 mRNA was not affected in DOX treated as compared to the control group (p>0.05). On the other hand, in the DOX-MTX NP treated group, fewer tumors characterized with advanced stage and decreased HER2 paralleled improved clinical outcome (P<0.05). Moreover, the effectiveness of the oral route in the group treated with nanodrug accounted for the enhanced bioavailability of nanoparticulated DOX-MTX compared to free DOX. Furthermore, there was no significant difference in mRNA level of HER2 (p>0.05). Conclusions: Influence of HER2 gene expression is a new feature and mechanism of action observed only in dual action DOX-MTX-NPs treated groups. Down-regulation of HER2 mRNA as a promising marker and prognosticator of OSCC adds to the cytotoxic benefits of DOX in its new formulation. Both oral and IV application of this nanodrug could be used, with no preferences in term of their safety or toxicity. As HER2 is expressed abundantly by a wide spectrum of tumors, i DOX-MTX NPs may be useful for a wide-spectrum of lesions. However, molecular mechanisms underlying HER2 down regulation induced by DOX-MTX NPs remain to be addressed.

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Nanoparticle-assisted Combination Therapies for Effective Cancer Treatment

Cited by 512 publications

References 69 publications

Polymersome-Mediated Delivery of Combination Anticancer Therapy to Head and Neck Cancer Cells: 2D and 3D in Vitro Evaluation

Polymersome-Mediated Delivery of Combination Anticancer Therapy to Head and Neck Cancer Cells: 2D and 3D in Vitro Evaluation

DOX-MTX-NPs Augment p53 mRNA Expression in OSCC Model in Rat: Effects of IV and Oral Routes

New formulated "DOX-MTX-loaded Nanoparticles" Down-regulate HER2 Gene Expression and Improve the Clinical Outcome in OSCCs Model in Rat: the Effect of IV and Oral Modalities

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