In Vitro and In Vivo Anticancer Activity of a Novel Nano-sized Formulation Based on Self-assembling Polymers Against Pancreatic Cancer

Hoskins, Clare; Ouaïssi, Mehdi; Lima, Sofia A. Costa; Cheng, Wenguang; Loureirio, Inês; Mas, Eric; Lagadic‐Gossmann, Dominique; Cordeiro-da-Silva, Anabela; Ouaissi, Ali; Lin, Paul Kong Thoo

doi:10.1007/s11095-010-0268-6

Cited by 29 publications

(31 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This result is presumably because more of the drug is entering the cell, as observed in the cellular uptake studies (Figure 5). This is in agreement with other studies in the literature, whereby, after encapsulation into a polymeric nanoparticle, greater intracellular trafficking of drug compounds is observed [26,27,28]. Additionally, formulation of this practically insoluble drug renders it more clinically useful, as aqueous preparations of injectables are preferred over oil or organics because of reduced pain on administration, as well as toxic side effects from the diluents.…”

Section: Discussionsupporting

confidence: 91%

Dual Acting Polymeric Nano-Aggregates for Liver Cancer Therapy

et al. 2018

Self Cite

View full text Add to dashboard Cite

Liver cancer treatments are often hindered by poor drug physicochemical properties, hence there is a need for improvement in order to increase patient survival and outlook. Combination therapies have been studied in order to evaluate whether increased overall efficacy can be achieved. This study reports the combined treatment of liver cancer cells with a combination treatment of chemotherapeutic agent paclitaxel and pro-apoptotic protein cytochrome C. In order to administer both agents in a single formulation, a poly(allylamine)-based amphiphile has been fabricated with the incorporation of a hybrid iron oxide-gold nanoparticle into its structure. Here, the insoluble paclitaxel becomes incorporated into the hydrophobic core of the self-assemblies formed in an aqueous environment (256 nm), while the cytochrome C attaches irreversibly onto the hybrid nanoparticle surface via gold-thiol dative covalent binding. The self-assemblies were capable of solubilising up to 0.698 mg/mL of paclitaxel (700-fold improvement) with 0.012 mg/mL of cytochrome C also attached onto the hybrid iron oxide-gold nanoparticles (HNPs) within the hydrophobic core. The formulation was tested on a panel of liver cancer cells and cytotoxicity was measured. The findings suggested that indeed a significant improvement in combined therapy (33-fold) was observed when compared with free drug, which was double the enhancement observed after polymer encapsulation without the cytochrome C in hepatocellular carcinoma (Huh-7D12) cells. Most excitingly, the polymeric nanoparticles did result in improved cellular toxicity in human endothelian liver cancer (SK-hep1) cells, which proved completely resistant to the free drug.

show abstract

Section: Discussionsupporting

confidence: 91%

Dual Acting Polymeric Nano-Aggregates for Liver Cancer Therapy

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…This aggregate increased drug solubilisation and resulted in more rapid drug uptake into pancreatic cancer BxPC-3 cells compared with the free drug. A similar clinical effect was experienced with the clinically used drug gemcitabine at 8-fold less dose [31].…”

Section: Introductionsupporting

confidence: 56%

Thermally triggered theranostics for pancreatic cancer therapy

et al. 2017

Self Cite

View full text Add to dashboard Cite

Hybrid iron oxide-gold nanoparticles (HNPs) are capable of drug binding onto their surface with a triggered release at elevated temperatures. The iron oxide core allows for diagnostic imaging whilst heating of the gold shell upon laser irradiation reverses drug binding. This study exploits the reversible binding of novel polyamine based drugs in order to provide specific and effective method for pancreatic cancer treatment. Here we used novel bisnaphthalamido (BNIP) based drug series. Our hybrid nanoparticles (50 nm) were capable of drug loading onto their surface (3:1:0.25, Drug:Fe:Au). By exploiting the surface-to-drug electrostatic interaction of a range of BNIP agents, heat triggered drug release was achieved.12-fold reduction in IC 50 after 24 h in vitro and 5-fold reduction of tumour retardation in vivo compared with free drug in pancreatic models after treatment with the HNP-formulation and laser irradiation. This heat activated system could provide a key platform for future therapy strategies.

show abstract

“…The reason for this is not clear, although it could be due to the increased core expansion upon drug loading resulting in larger aggregates which were then removed during the filtering process. Other studies reported cholesterol modified PAA (Ch5) for BNIPDaoct solubilisation achieved 0.3 mgmL -1 drug encapsulation with 1 mgmL -1 polymer concentration, 5% mole cholesterol grafting and a 1:1 initial drug:polymer mass feed ratio [49]. Here, the PAA-Ox5-HNP formulation achieved a greater drug loading (0.9 mgmL -1 ) but with a lower % loading capacity (15% compared to the 30%) to the Ch5-BNIPDaoct formulation.…”

Section: Discussionmentioning

confidence: 99%

“…However, the added hydrophobicity of the drug molecule into the intrinsic structure of the nano-aggregate may be enough to stabilize the system. Little is known in this area as previous studies have observed that even at polymer concentrations below IC 50 in vivo enhancement in drug efficacy occurs [49]. 50 between free drug and formulation (p<0.001).…”

Section: Discussionmentioning

confidence: 99%