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In this content, a small molecular ligand of prostate specific membrane antigen (SMLP) conjugated poly (caprolactone) (PCL)-b-poly (ethylene glycol) (PEG) copolymers with different block lengths were synthesized to construct a satisfactory drug delivery system. Four different docetaxel-loaded polymeric micelles (DTX-PMs) were prepared by dialysis with particle sizes less than 60 nm as characterized by dynamic light scattering (DLS) and transmission electron microscope (TEM). Optimization of the prepared micelles was conducted based on short-term stability and drug-loading content. The results showed that optimized systems were able to remain stable over 7 days. Compared with Taxotere, DTX-PMs with the same ratio of hydrophilic/hydrophobic chain length displayed similar sustained release behaviors. The cytotoxicity of the optimized targeted DTX-PCL12K-PEG5K-SMLP micelles (DTX-PMs2) and non-targeted DTX-PCL12K-mPEG5K micelles (DTX-PMs1) were evaluated by MTT assays using prostate specific membrane antigen (PSMA) positive prostate adenocarcinoma cells (LNCaP). The results showed that the targeted micelles had a much lower IC50 than their non-targeted counterparts (48 h: 0.87±0.27 vs 13.48±1.03 µg/ml; 72 h: 0.02±0.008 vs 1.35±0.54 µg/ml). In vitro cellular uptake of PMs2 showed 5-fold higher fluorescence intensity than that of PMs1 after 4 h incubation. According to these results, the novel nano-sized drug delivery system based on DTX-PCL-PEG-SMLP offers great promise for the treatment of prostatic cancer.

Abstract:In this work, micelles composed of doxorubicin-conjugated Y-shaped copolymers (YMs) linked via an acid-labile linker were constructed. Y-shaped copolymers of mPEG-b-poly(glutamate-hydrazone-doxorubicin) 2 and linear copolymers of mPEG-b-poly(glutamate-hydrazone-doxorubicin) were synthesized and characterized. Particle size, size distribution, morphology, drug loading content (DLC) and drug release of the micelles were determined. Alterations in size and DLC of the micelles could be achieved by varying the hydrophobic block lengths. Moreover, at fixed DLCs, YMs showed a smaller diameter than micelles composed of linear copolymers (LMs). Also, all prepared micelles showed sustained release behaviors under physiological conditions over 72 h. DOX loaded in YMs was released more completely, with 30% more drug released in acid. The anti-tumor efficacy of the micelles against HeLa cells was evaluated by MTT assays, and YMs exhibited stronger cytotoxic effects than LMs in a dose-and time-dependent manner. Cellular uptake studied by CLSM indicated that YMs and LMs were readily taken up by HeLa cells. According to the results of this study, doxorubicin-conjugated Y-shaped PEG-(polypeptide) 2 copolymers showed advantages over linear copolymers, like assembling into smaller nanoparticles, faster drug release in acid, which may correspond to higher OPEN ACCESSMolecules 2014, 19 11916 cellular uptake and enhanced extracellular/intracellular drug release, indicating their potential in constructing nano-sized drug delivery systems.

Synthetic nanofibrillar hydrogels resembling a natural extracellular matrix have emerged as a promising material in the biomedical field; however, achievement of multifunctional nanofibrillar hydrogels with good biocompatibility is still an important and challenging task. Herein, we report a fluorescent nanofibrillar hydrogel prepared with polyethyleneimine (PEI) and cellulose nanocrystals (CNCs) via one-step hydrothermal treatment. The nanofibrillar hydrogels are mainly formed from CNCs cross-linked by carbon dots (CDs) through hydrogen bonding and hydrophobic interactions. The nanostructures and the mechanical properties of the hydrogels are controlled by weight ratios of CNCs to PEI and the total concentration of CNCs and PEI. In comparison with other hydrogels from CNCs and CDs, the nanofibrillar hydrogels exhibit better mechanical properties with relatively high Young’s moduli. The hydrogels show relatively low cytotoxicity and good biocompatibility, which are demonstrated by in vitro cell culture and in vivo subcutaneous implantation in rats. This work provides a new approach to prepare biomimetic nanofibrillar hydrogels with fluorescence properties, thus offering a promising synthetic material resembling a natural extracellular matrix for bioapplications.

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