Enzymatic synthesis of PEGylated lactide-diester-diol copolyesters for highly efficient targeted anticancer drug delivery
MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS
Authors: Su, Meifei; Xie, Jianhua; Zeng, Qiang; Shu, Man; Liu, Jie; Jiang, Zhaozhong
Abstract
PEGylated lactide-diester-diol copolymers were successfully synthesized via lipase-catalyzed copolymerization, the resultant amphiphilic PEG-poly(L-lactate-co-hexamethylene-co-adipate) (PEG-PLLHA) and PEG-poly(D,L-lactate-co-hexamethylene-co-adipate) (PEG-PDLLHA) block copolymers readily undergo self-assembly processes to form nanosized micelles in aqueous medium, which are stable under physiological conditions in the presence of serum proteins. By conjugating folic acid (FA) to enzymatic synthesized poly(hexamethylene adipate-co-hexamethylene 2,3-epoxy succinate), we could formulate FA-bearing PEG-polyester micelles for docetaxel (DTX) targeting delivery. FA-PEG-PLLHA and FA-PEG-PDLLHA micelles possess efficient cell-targeting capability toward FA receptor-positive cancer cells (e.g., CT-26), which significantly enhances their cellular uptake rates and efficacy of drug-loaded formulations toward such cells. During in vivo anticancer treatments, the FA-bearing micelles are highly capable of targeting and accumulating preferentially in tumor tissues by both active cell-targeting mechanism and passive targeting via the EPR effect. All these desirable properties enable the FA-bearing micelles to deliver DTX with 97% tumor-inhibiting efficiency through systemic delivery, which is favorable in comparison to the values of various DTX nanoparticle formulations reported in literature. Importantly, biosafety assays reveal that all DTX-loaded micelles are biocompatible and safe for in vivo antitumor treatment applications. Thus, FA-PEG-PLLHA and FA-PEG-PDLLHA micelles represent new types of promising anticancer drug nanocarriers for targeted chemotherapy.
Visible/Near-Infrared Emitting, Garnet-Based Paramagnetic-Persistent Luminescent Nanocrystals for Two-Photon Bioimaging
CRYSTAL GROWTH & DESIGN
Authors: Sengar, Prakhar; Flores, Dora-Luz; Chauhan, Kanchan; Can-Uc, Bonifacio; Juarez-Moreno, Karla; Contreras, Oscar E.; Digman, Michelle A.; Hirata, Gustavo A.
Abstract
Multimode bioimaging using a combination of two or more imaging techniques is beneficial for taking advantage of each modality by overcoming the individual limitations. It allows visualization of diseased tissue with high specificity making it a powerful strategy for improved disease prognosis. Herein, we report a multimodality probe, Gd2.99Ce0.01Al1.995Cr0.005Ga3O12 (GAGG:Ce,Cr), combining magnetic, persistent luminescence, and nearinfrared (NIR) to NIR two-photon excited bioimaging properties. The hydrothermally synthesized GAGG:Ce,Cr with an average size of similar to 100 nm exhibited persistent luminescence emission in both visible and NIR regions upon blue light excitation. Besides, the nanoparticles (NPs) demonstrated paramagnetic properties with a magnetic susceptibility of 4.6 x 10(-5) emu/gOe. Folic acid functionalized NPs (GAGG:CeCr-FA) showed retained characteristic visible emission of Ce3+ similar to 550 nm and NIR emission of Cr3+ similar to 720 nm upon excitation with two photons (800 nm). In vitro toxicity analysis of nanoparticles in different cell lines revealed the biocompatible nature before and after surface modification. GAGG:CeCr-FA NPs were efficiently internalized in HeLa cells and presented multiphotonic emission in the visible and NIR regions after two-photon NIR (800 nm) excitation. This study suggests that NIR -> NIR two-photon excited magneto-persistent GAGG:CeCr is a potential multifunctional nanoprobe for deep penetration and high contrast bioimaging.