A mixed micellar system of novel function was designed and synthesized by co-assembling TAT (cell penetrating peptide)-modified poly (ethylene glycol)-poly(l-lactide) (PEG-PLA) copolymer with the drug-conjugated poly(ethylene glycol)-b-poly(l-lactide-co-2-methyl-2-carboxyl-propylene carbonate) (mPEG-b-P(LA-co-MCC)) copolymer. UV-Vis, Matrix-assisted laser desorption/ionization time-of-flight, and XPS were used to ensure the successful modification of the copolymers with TAT and anti-tumor drugs. The size of spherical nanomicelles increased from 50 to 60 nm as of empty polymeric micelles to 100–150 nm as of drug-loaded ones, determined by dynamic light scattering and TEM. Daunorubicin was selected as model drug for in vitro evaluations on different cell lines. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay clearly indicated an improved cell growth inhibition of the TAT-modified mixed micelles. While green fluorescent protein was used as a marker for the mixed micelle, small amount of DMSO was necessary to enhance the accumulation of the mixed micelles in cell lines Caski. Mediated by TAT, mixed micelles containing Apoptin (a tumor-specific apoptosis drug) showed higher level of tumor cell internalization and growth inhibition than that of mixed micelles without TAT modification. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 4598–4607, 2013

Novel polyesters, poly[(ε-caprolactone)-co-(N-trityl-L-serine-β-lactone)]s, were prepared by copolymerizing ε-caprolactone (CL) with N-trityl-L-serine-β-lactone (TSL) using ZnEt₂ as the catalyst. The number-average molecular weights were determined which ranged from 2.7 × 10⁴ to 4.9 × 10⁴ Da with dispersity values ranging from 1.6 to 1.8. The structures of the copolymers were investigated by means of ¹H NMR, ¹³C NMR and infrared spectroscopies, thermogravimetric analysis and differential scanning calorimetry. The results indicated that CL and TSL monomer units were randomly distributed within the copolymer backbone structures and the ratios of TSL to CL in the copolymers were close to those in the feeds. After removal of the trityl group under mild condition, a new polyester with side amino groups provided by serine units was obtained. L929 cell culturing test indicated good biocompatibility of the polyester with or without protective groups. © 2012 Society of Chemical Industry

Stimuli-responsive micellar nanoparticles are gaining considerable attention in the field of drug delivery because of their great advantages of high efficiency in tumor accumulation through the enhanced permeability and retention effect and rapid drug release. In this study, a novel catechol moiety-containing amphiphilic, biodegradable polymeric carrier, monomethoxy poly(ethylene glycol)-block-poly(ε-caprolactone)-block-poly(L-lysine)-graft-[3-(3,4-dihydroxyphenyl)propionic acid], was employed for delivery of the anticancer drug bortezomib (BTZ) to cancer cells. The strategy is based on the facile conjugation of BTZ to catechol-containing polymeric carriers through boronate formation, which could dissociate in acidic environments to liberate its payload BTZ to inhibit proteasome function. This reducing BTZ–catechol interaction with decreasing pH value was demonstrated by microcalorimetry analysis using isothermal titration calorimetry. Notably, the obtained micellar BTZ complex that self-assembled from drug-loaded amphiphilic polymer was internalized effectively by MCF-7 breast cancer cells and resulted in significant 26S proteasome inhibition. Furthermore, the micellar BTZ complex induced remarkable apoptosis on MCF-7 and HeLa cancer cells and exhibited little toxicity on HEK293 normal cells. More importantly, systemic delivery of micellar BTZ complex prolonged its blood circulation and resulted in significant accumulation in the tumor site relative to free drug, thus suggesting therapeutic promise for micellar BTZ delivery in cancer therapy.

A zinc-based catalyst zinc bis[bis(trimethylsilyl)amide] was used for the polymerization of cyclic esters including L-lactide (L-LA) and 2-methyl-2-carboxyl-propylene carbonate (MBC). The polymerization of L-lactide in THF could be carried out successfully under mild conditions in very short time by using the zinc catalyst and alcohols as the initiators. Kinetic study in solution polymerization prooved the polymerization has high monomer conversion degree close to 100% and the molecular weight of the resulting polyester has linear increase with the increase of [M]₀ /[I] (molar ratio of monomer to initiator). Sequential polymerization of L-LA and MBC in THF also showed high MBC conversion of 94% with a narrow molecualr weight maintained, indicating a living nature of this polymerization. The zinc catalyst system has also been used for the L-LA bulk polymerization with a high monomer conversion. ¹³C NMR indicated the polymer possesses high regioregularity and the minor regioirregular component was owing to the D-LA in the monomer inserted into the polymer mainchain during the transesterifcation. Interaction between monomer and zinc catalyst has been found to be a key factor to sustain a homogenous solution during the initiating procedure. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

Amphiphilic triblock copolymers were synthesized using MPEG, cyclic carbonic ester monomer including propargyl group (MPC) and L-lactide (LA). These copolymers could self-assemble into core–shell spherical micelles with propargyl groups on the surface. Azided hemoglobin (Hb) was conjugated with the micelles through click reaction to form Hb-bearing nano-micelles. The click reaction conditions, such as the molar ratio of sodium azide to Hb, the binding ratio of Hb to copolymers, the components of catalytic solution, the reaction temperature and time, were thoroughly investigated and optimized. The resulted nano-micelles had 100 nm diameter with 50–60 wt% of Hb content. The Hb-based nano-micelles showed appropriate stability and oxygen carrying capacity, and would have the potential to be used as the new type of artificial oxygen carrier. Copyright © 2011 John Wiley & Sons, Ltd.