Smart multifunctional core-shell nanospheres with drug and gene co-loaded for enhancing the therapeutic effect in a rat intracranial tumor model

• Published in: Nanoscale 2012-10, Vol.4 (20), p.6501-6508
• Main Authors: Wang, HanJie, Su, Wenya, Wang, Sheng, Wang, Xiaomin, Liao, Zhenyu, Kang, Chunsheng, Han, Lei, Chang, Jin, Wang, Guangxiu, Pu, Peiyu
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacokinetics; Brain Neoplasms - drug therapy; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Cancer; Cell Line, Tumor; Cell Survival - drug effects; Construction; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug Carriers - pharmacokinetics; Drug Delivery Systems; Drugs; Epirubicin - administration & dosage; Epirubicin - chemistry; Epirubicin - pharmacokinetics; Gene Transfer Techniques; Genes; Glioblastoma - drug therapy; Glioblastoma - metabolism; Glioblastoma - pathology; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Humans; Lactic Acid - administration & dosage; Lactic Acid - chemistry; Magnetite Nanoparticles; Nanomaterials; Nanospheres; Nanospheres - chemistry; Nanostructure; Peptides; Plasmids - administration & dosage; Plasmids - genetics; Plasmids - pharmacokinetics; Polyglycolic Acid - administration & dosage; Polyglycolic Acid - chemistry; Rats; Spectroscopy, Fourier Transform Infrared; Stomach - cytology; Stomach - drug effects; Xenograft Model Antitumor Assays
• ISSN: 2040-3364; 2040-3372
• DOI: 10.1039/c2nr31263h

Glioblastoma with high mortality has been one of the most serious cancers threatening human health. Because of the present treatment limitations, there is an urgent need to construct a multifunctional vesicle for enhancing the treatment of in situ malignant glioblastoma. In our study, drug and gene co-loaded magnetic PLGA/multifunctional polymeric liposome (magnetic PLGA/MPLs) core-shell nanospheres were constructed. They were mainly self-assembled from two parts: hydrophobic PLGA cores that can load drugs and magnetic nanocrystals; and polymeric lipid shells anchored with functional molecules such as PEG chains, TAT peptides and RGD peptides that can help the vectors to condense the gene, prolong the circulation time, cross the blood brain barrier and target delivery to the cancer tissue. The results showed that the magnetic PLGA/MPLs nanosphere has a nanosized core-shell structure, can achieve sustained drug release and has good DNA binding abilities. Importantly, compared with the control group and other groups with single functionality, it can co-deliver the drug and gene into the same cell in vitro and show the strongest inhibiting effect on the growth of the in situ malignant glioblastoma in vivo. All of these results indicated that the different functional components of magnetic PLGA/MPLs, can form an organic whole and none of them can be dispensed with. The magnetic PLGA/MPLs nanosphere may be another option for treatment of glioblastoma.