Dataset Information

Small-sized polymeric micelles incorporating docetaxel suppress distant metastases in the clinically-relevant 4T1 mouse breast cancer model.

ABSTRACT:

Background

The small size of ultra-small nanoparticles makes them suitable for lymphatic delivery, and many recent studies have examined their role in anti-metastasis therapy. However, the anti-metastatic efficacy of small-sized nanocarriers loaded with taxanes such as docetaxel has not yet been investigated in malignant breast cancer.

Methods

We encapsulated docetaxel using poly(D,L-lactide)1300-b-(polyethylene glycol-methoxy)2000 (mPEG2000-b-PDLLA1300) to construct polymeric micelles with a mean diameter of 16.76 nm (SPM). Patient-like 4T1/4T1luc breast cancer models in Balb/c mice, with resected and unresected primary tumors, were used to compare the therapeutic efficacies of SPM and free docetaxel (Duopafei) against breast cancer metastasis using bioluminescent imaging, lung nodule examination, and histological examination.

Result

SPM showed similar efficacy to Duopafei in terms of growth suppression of primary tumors, but greater chemotherapeutic efficacy against breast cancer metastasis. In addition, lung tissue inflammation was decreased in the SPM-treated group, while many tumor cells and neutrophils were found in the Duopafei-treated group.

Conclusion

Small-sized mPEG2000-b-PDLLA1300 micelles could provide an enhanced method of docetaxel delivery in breast cancer metastasis, and may represent a valid chemotherapeutic strategy in breast cancer patients with resected primary tumors.

SUBMITTER: Li Y

PROVIDER: S-EPMC4023534 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Small-sized polymeric micelles incorporating docetaxel suppress distant metastases in the clinically-relevant 4T1 mouse breast cancer model.

Li Yunfei Y Jin Mingji M Shao Shuai S Huang Wei W Yang Feifei F Chen Wei W Zhang Shenghua S Xia Guimin G Gao Zhonggao Z

BMC cancer 20140510

<h4>Background</h4>The small size of ultra-small nanoparticles makes them suitable for lymphatic delivery, and many recent studies have examined their role in anti-metastasis therapy. However, the anti-metastatic efficacy of small-sized nanocarriers loaded with taxanes such as docetaxel has not yet been investigated in malignant breast cancer.<h4>Methods</h4>We encapsulated docetaxel using poly(D,L-lactide)1300-b-(polyethylene glycol-methoxy)2000 (mPEG2000-b-PDLLA1300) to construct polymeric mic ...[more]

PMID: 24885518

Similar Datasets

Project description:RNA interference (RNAi) drugs have significant therapeutic potential, but delivery systems with appropriate efficacy and toxicity profiles are still needed. Here, we describe a neutral, ampholytic polymeric delivery system based on conjugatable diblock polymer micelles. The diblock copolymer contains a hydrophilic poly[N-(2-hydroxypropyl)methacrylamide-co-N-(2-(pyridin-2-yldisulfanyl)ethyl)methacrylamide) (poly[HPMA-co-PDSMA]) segment to promote aqueous stability and facilitate thiol-disulfide exchange reactions and a second ampholytic block composed of propylacrylic acid (PAA), dimethylaminoethyl methacrylate (DMAEMA), and butyl methacrylate (BMA). The poly[(HPMA-co-PDSMA)-b-(PAA-co-DMAEMA-co-BMA)] was synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization with an overall molecular weight of 22 000 g/mol and a PDI of 1.88. Dynamic light scattering and fluorescence measurements indicated that the diblock copolymers self-assemble under aqueous conditions to form polymeric micelles with a hydrodynamic radius and critical micelle concentration of 25 nm and 25 μg/mL, respectively. Red blood cell hemolysis experiments show that the neutral hydrophilic micelles have potent membrane destabilizing activity at endosomal pH values. Thiolated siRNA targeting glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was directly conjugated to the polymeric micelles via thiol exchange reactions with the pyridal disulfide groups present in the micelle corona. Maximum silencing activity in HeLa cells was observed at a 1:10 molar ratio of siRNA to polymer following a 48 h incubation period. Under these conditions 90% mRNA knockdown and 65% protein knockdown at 48 h was achieved with negligible toxicity. In contrast the polymeric micelles lacking a pH-responsive endosomalytic segment demonstrated negligible mRNA and protein knockdown under these conditions. The potent mRNA knockdown and excellent biocompatibility of the neutral siRNA conjugates demonstrate the potential utility of this carrier design for delivering therapeutic siRNA drugs.

Dataset Information

Small-sized polymeric micelles incorporating docetaxel suppress distant metastases in the clinically-relevant 4T1 mouse breast cancer model.

Background

Methods

Result

Conclusion

Publications

Small-sized polymeric micelles incorporating docetaxel suppress distant metastases in the clinically-relevant 4T1 mouse breast cancer model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets