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A novel and versatile family of enzymaticallyand reductively degradableα-amino acid-based poly(ester amide)s (SS-PEAs) were developedfrom solution polycondensation of disulfide-containing di-p-toluenesulfonic acid salts of bis-l-phenylalaninediesters (SS-Phe-2TsOH) with di-p-nitrophenyl adipate(NA) in N,N-dimethylformamide (DMF).SS-PEAs with Mnranging from 16.6 to 23.6kg/mol were obtained, depending on NA/SS-Phe-2TsOH molar ratios. Thechemical structures of SS-PEAs were confirmed by 1H NMRand FTIR spectra. Thermal analyses showed that the obtained SS-PEAswere amorphous with a glass transition temperature (Tg) in the range of 35.2–39.5 °C. The in vitrodegradation studies of SS-PEA films revealed that SS-PEAs underwentsurface erosion in the presence of 0.1 mg/mL α-chymotrypsinand bulk degradation under a reductive environment containing 10 mMdithiothreitol (DTT). The preliminary cell culture studies displayedthat SS-PEA films could well support adhesion and proliferation ofL929 fibroblast cells, indicating that SS-PEAs have excellent cellcompatibility. The nanoparticles prepared from SS-PEA with PVA asa surfactant had an average size of 167 nm in phosphate buffer (PB,10 mM, pH 7.4). SS-PEA nanoparticles while stable under physiologicalenvironment undergo rapid disintegration under an enzymatic or reductivecondition. The in vitro drug release studies showed that DOX releasewas accelerated in the presence of 0.1 mg/mL α-chymotrypsinor 10 mM DTT. Confocal microscopy observation displayed that SS-PEAnanoparticles effectively transported DOX into both drug-sensitiveand -resistant MCF-7 cells. MTT assays revealed that DOX-loaded SS-PEAnanoparticles had a high antitumor activity approaching that of freeDOX in drug-sensitive MCF-7 cells, while more than 10 times higherthan free DOX in drug-resistant MCF-7/ADR cells. These enzymaticallyand reductively degradable α-amino acid-based poly(ester amide)shave provided an appealing platform for biomedical technology in particularcontrolled drug delivery applications. [ABSTRACT FROM AUTHOR]

Reduction-sensitive reversibly core-cross-linked micellesweredeveloped based on poly(ethylene glycol)-b-poly(N-2-hydroxypropyl methacrylamide)–lipoic acid (PEG-b-PHPMA-LA) conjugates and investigated for triggered doxorubicin(DOX) release. Water-soluble PEG-b-PHPMA block copolymerswere obtained with Mn,PEGof 5.0 kg/moland Mn,HPMAvarying from 1.7 and 4.1 to7.0 kg/mol by reversible addition–fragmentation chain transfer(RAFT) polymerization. The esterification of the hydroxyl groups inthe PEG-b-PHPMA copolymers with lipoic acid (LA)gave amphiphilic PEG-b-PHPMA-LA conjugates with degreesof substitution (DS) of 71–86%, which formed monodispersedmicelles with average sizes ranging from 85.3 to 142.5 nm, dependingon PHPMA molecular weights, in phosphate buffer (PB, 10 mM, pH 7.4).These micelles were readily cross-linked with a catalytic amount ofdithiothreitol (DTT). Notably, PEG-b-PHPMA(7.0k)-LAmicelles displayed superior DOX loading content (21.3 wt %) and loadingefficiency (90%). The in vitro release studies showed that only about23.0% of DOX was released in 12 h from cross-linked micelles at 37°C at a low micelle concentration of 40 μg/mL, whereasabout 87.0% of DOX was released in the presence of 10 mM DTT underotherwise the same conditions. MTT assays showed that DOX-loaded core-cross-linkedPEG-b-PHPMA-LA micelles exhibited high antitumoractivity in HeLa and HepG2 cells with low IC50(half inhibitoryconcentration) of 6.7 and 12.8 μg DOX equiv/mL, respectively,following 48 h incubation, while blank micelles were practically nontoxicup to a tested concentration of 1.0 mg/mL. Confocal laser scanningmicroscope (CLSM) studies showed that DOX-loaded core-cross-linkedmicelles released DOX into the cell nuclei of HeLa cells in 12 h.These reduction-sensitive disassemblable core-cross-linked micelleswith excellent biocompatibility, superior drug loading, high extracellularstability, and triggered intracellular drug release are promisingfor tumor-targeted anticancer drug delivery. [ABSTRACT FROM AUTHOR]