Multifunctional Cholesterol-modified Dendrimers for Targeted Drug Delivery to Cancer Cells Expressing Folate Receptors

We present here the development of cholesterol(Chol)-modified dendrimer system for targeted chemotherapy of folate(FA)receptor-expressing cancer cells. In our study, poly(amidoamine)(PAMAM) dendrimers of generation 5(G5) were functionalized stepby-step with Chol, fluorescein isothiocyanate(FI), and FA via a poly(ethylene glycol)(PEG) spacer(PEG-FA), and then acetamide to shield their remaining surface amines. The synthesized G5.NHAc-Chol-FI-PEG-FA(for short, G5-CFPF) dendrimers were utilized to encapsulate 10-hydroxycamptothecin(HCP), a hydrophobic anticancer drug. We find that each G5-CFPF dendrimer can encapsulate 13.8 HCP molecules. The complexes show a slower release profiles of HCP in a pH-dependent manner than the control complexes formed using the same dendrimers without Chol under the same conditions. Thanks to the targeting role played by FA, the complexes display a specific inhibition efficacy to FA receptor-expressing cervical cancer cells. The designed Chol-modified dendrimers may be adopted as a promising carrier for application in targeted cancer therapy.

Folic Acid Modified Electrospun Poly(vinyl alcohol)/Polyethyleneimine Nanofibers for Cancer Cell Capture Applications

Capture and detection of metastatic cancer cells are crucial for diagnosis and treatment of malignant neoplasm. Here, we report the use of folic acid （FA） modified electrospun poly（vinyl alcohol） （PVA）/polyethyleneimine （PEI） nanofibers for cancer cell capture applications. Electrospun PVA/PEI nanofibers crosslinked by glutaraldehyde vapor were modified with FA via a poly（ethylene glycol） （PEG） spacer, followed by acetylation of the fiber surface PEI amines. The formed FA-modified nanofibers were well characterized. The morphology of the electrospun PVA/PEI nanofibers is smooth and uniform despite the surface modification. In addition, the FA-modified nanofibers display good hemocompatibility as confirmed by hemolysis assay. Importantly, the developed FA-modified nanofibers are able to specifically capture cancer cells overexpressing FA receptors, which were validated by quantitative cell counting assay and qualitative confocal microscopy analysis. The developed FA-modified PVA/PEI nanofibers may be used for capturing circulating tumor cells for cancer diagnosis applications.

Controlled Release of Doxorubicin from Electrospun MWCNTs/PLGA Hybrid Nanofibers

In this study, multiwalled carbon nanotubes （MWCNTs） were used to encapsulate a model anticancer drug, doxorubicin （Dox）. Then, the drug-loaded MWCNTs （Dox/MWCNTs） with an optimized drug encapsulation percentage were mixed with poly（lactide-co-glycolide） （PLGA） polymer solution for subsequent electrospinning to form drug-loaded composite nanofibrous mats. The structure, morphology, and mechanical properties of the formed electrospun Dox/PLGA, MWCNTs/PLGA, and Dox/MWCNTs/PLGA composite nanofibrous mats were characterized using scanning electron microscopy （SEM）, Fourier transform infrared spectroscopy, and tensile testing. In vitro viability assay and SEM morphology observation of mouse fibroblast cells cultured onto the MWCNTs/PLGA fibrous scaffolds demonstrate that the developed MWCNTs/PLGA composite nanofibers are cytocompatible. The incorporation of Dox-loaded MWCNTs within the PLGA nanofibers is able to improve the mechanical durability and maintain the three-dimensional structure of the nanofibrous mats. More importantly, our results indicate that this double-container drug delivery system （both PLGA polymer and MWCNTs are drug carriers） is beneficial to avoid the burst release of the drug and able to release the antitumor drug Dox in a sustained manner for 42 days. The developed composite electrospun nanofibrous drug delivery system may be used as therapeutic scaffold materials for post-operative local chemotherapy.