Polymeric Nanomedicine for Combined Gene/Chemotherapy Elicits Enhanced Tumor Suppression
| Autor: | Shaohua Yao, Jun Zeng, Shuangzhi Li, Fazhan Wang, Bei Xu, Yan Chen, Xiangrong Song, Ting Yu, Xiaoyue Tan, Yongmei Liu, Shan Xia, Ke Ren, Quansheng Jin, Lili He |
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| Rok vydání: | 2016 |
| Předmět: |
Male
Lung Neoplasms Polymers medicine.medical_treatment Fluorescent Antibody Technique Pharmaceutical Science Apoptosis 02 engineering and technology Pharmacology Immunoenzyme Techniques Mice chemistry.chemical_compound Drug Delivery Systems 0302 clinical medicine Cell Movement Drug Discovery Tumor Cells Cultured Mice Inbred BALB C Reverse Transcriptase Polymerase Chain Reaction Cell Cycle Cell cycle 021001 nanoscience & nanotechnology Combined Modality Therapy Nanomedicine Paclitaxel 030220 oncology & carcinogenesis Colonic Neoplasms Molecular Medicine 0210 nano-technology Combination therapy Blotting Western Real-Time Polymerase Chain Reaction 03 medical and health sciences PEDF medicine Animals Humans Nerve Growth Factors RNA Messenger Eye Proteins Serpins Cell Proliferation A549 cell Chemotherapy Cell growth Antineoplastic Agents Phytogenic Xenograft Model Antitumor Assays chemistry Nanoparticles |
| Zdroj: | Molecular Pharmaceutics. 13:663-676 |
| ISSN: | 1543-8392 1543-8384 |
| DOI: | 10.1021/acs.molpharmaceut.5b00922 |
| Popis: | Combination treatment through simultaneous delivery of DNA and anticancer drugs with nanoparticles has been demonstrated to be an elegant and efficient approach for cancer therapy. Herein, we employed a combination therapy for eliminating both the tumor cells and intratumoral neovascular network based on the nanoplatform we designed. Pigment epithelium-derived factor (PEDF) gene, a powerful antiangiogenic agent, and the clinically widely used chemotherapy agent paclitaxel (PTX) were simultaneously encapsulated in the same nanoparticle by a modified double-emulsion solvent evaporation method. The dual-drug-loaded nanoparticles (D/P-NPs) exhibited a uniform spherical morphology and released PTX and PEDF gene in a sustained manner. D/P-NPs showed an enhanced antitumor effect on C26 and A549 cells and a stronger inhibitory activity on proliferation of HUVECs. Moreover, D/P-NPs could dramatically elevate the PEDF expression levels in both C26 and A549 cells in comparison with PEDF gene loaded nanoparticles and significantly promote the cellular uptake of PTX. Additionally, microtubules were stabilized and G2/M phase arrest along with a higher subG1 cell population was induced by D/P-NPs in contrast to PTX or PTX loaded nanoparticles. Besides, D/P-NPs showed sustained release of PTX and PEDF gene in tumors as well as long-term gene expression. A significantly improved anticancer effect was also demonstrated in a C26 subcutaneous tumor model using this combinational therapy. D/P-NPs could sharply reduce the microvessel density and significantly promoted tumor cell apoptosis in vivo. More importantly, the in vivo distribution, serological and biochemical analysis, and HE staining revealed that D/P-NPs had no obvious toxicity. Our study suggested that this novel polymeric nanomedicine had great potential for improving the therapeutic efficacy of combined gene/chemotherapy of cancer. |
| Databáze: | OpenAIRE |
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