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A polymer micelle-based drug delivery system has faced many challenges due to the lack of stability especially after being diluted in blood, resulting in a premature release. Herein, we developed camptothecin (CPT)-conjugated prodrug (CPTP) micelles in which CPT was grafted to the poly(ethylene glycol)-poly(glutamic acid) block copolymer via a disulfide bond linker for a redox-triggered drug release. Then, the cisplatin (CDDP)-crosslinked CPT-prodrug micelles (CPTP/CDDP) with a hybrid complex as a stable structure were successfully established via the CDDP (Pt)-carboxyl (COOH) chelate interaction. The resulting dual CPTP/CDDP had an average hydrodynamic radius of about 50 nm with a narrow distribution, which was conducive to the promotion of solid tumor accumulation. Importantly, CPT chemical bonding to the polymer backbone obviously stabilizes the CPT-prodrug micelles and prolongs their circulation time. Moreover, both CPT and CDDP are clinically used antitumor drugs; CDDP not only behaves as an ancillary anticarcinogen but also serves as a crosslinker to restrain the untimely burst release of CPT and to achieve synergistic antitumor efficacy. In addition, the CPTP/CDDP also exhibited a sustained reduction responsive release of CPT accompanied by the dissociation of the CDDP-COOH complex. This design ingeniously solved the contradiction between the stability and release of polymer micelle-based nanomedicines. Both in vitro and in vivo tests demonstrated an amazing antineoplastic efficacy compared with free drugs (CPT or CDDP) and just their physical mixing, indicating great promise for cancer treatment.

Poly(amino acid)-type macromolecules (PAAs), poly(ethylene glycol)-b-poly(aspartic acid) (PEG-PAAs), and poly(ethylene glycol)-b-poly(glutamic acid) (PEG-PGAs) were synthesized, and their states in aqueous solutions were studied. PEG-PAAs and PEG-PGAs were first used as novel polycarboxylate superplasticizers, and their dispersion and adsorption behaviors were investigated in cement slurries in the absence and presence of montmorillonite (MMT) clay. The results demonstrated that both PEG-PAAs and PEG-PGAs not only showed excellent water reducing and fluidity retention capabilities but also exhibited remarkable MMT clay tolerance. In contrast to the stretched molecular conformation of traditional polycarboxylate superplasticizers (PCEs), the hydrophobic main chain and the side methylene and ethylene linkers connected to the carboxylic groups of PAA and PGA segments resulted in self-assembly of the PEG-PAAs and PEG-PGAs in aqueous solutions, and the self-assembled nanosized aggregates exhibited relatively uniform spherical morphologies with average sizes of 30–100 nm. Carboxylic groups located on the periphery of the nanoaggregates acted as anchors and adsorbed on the surfaces of the cement particles. The nanoaggregates and the stretched hydrophilic PEG side chains, which jointly produced and enhanced the steric hindrance to prevent cement particle aggregation and hydration, resulted in notable dispersion capabilities. Total organic carbon (TOC), X-ray diffraction (XRD), and thermogravimetry–differential scanning calorimetry (TG-DSC) analyses revealed that the adsorption between the MMT clay and PAA nanoaggregates was surface adsorption (rather than interlayer adsorption), and this significant finding could be ascribed to the enlarged steric hindrance of the PAA nanoaggregates, which prevented the interlamination adsorption consumption of MMT clay to PAAs and revealed the outstanding clay insensitivity. This study provides a new perspective and strategy to design novel poly(amino acid)-type superplasticizers (PAAs) with excellent dispersion performances and improved clay tolerance.